QSE 5 — Process Control

Key Concepts

Key Concepts: This QSE covers the organization’s operations and production functions. It describes the need to ensure that this work is controlled, that processes function as expected, and that expected outcomes are met. This QSE encapsulates what occurs in each organization and forms the basis of its accreditation.

Key Terms
Change Control: A structured method of revising a policy, process, or procedure, including hardware or software design, transition planning, and revisions to all related documents.

Critical Equipment/Materials/Tasks: A piece of equipment, material, service, or task that can affect the quality of the organization’s products or services.

Executive Management: The highest-level personnel within an organization, including employees, clinical leaders, and independent contractors, who have responsibility for the operations of the organization and who have the authority to establish or change the organization’s quality policy. Executive management may be an individual or a group of
individuals.

Process Control: Activities designed to ensure that processes are stable and consistently operate within acceptable limits of variation in order to produce predictable output that meets specifications.

Product: A tangible output from a process.

Reference Standard: Specified requirements defined by the AABB. Reference standards define how or within what parameters an activity shall be performed and are more detailed than quality system requirements.

Service (noun): An intangible output of a process.

Service (verb): An action that leads to the creation of a product or a result that can affect donors, patients, and/or recipients.

Standard: A set of specified requirements upon which an organization may base its criteria for the products, components, and/or services provided.

Validation: Establishing evidence that a process, executed by users in their environment, will consistently meet predetermined specifications.

Verification: Confirmation by examination and provision of objective evidence that specified requirements have been met.

Examples of Objective Evidence:

• Policies, processes, and procedures related to this chapter.
• Implementation records.
• Records enabling traceability.
• Storage records.
• Quality control records.
• Process planning, process validation, and change control records.
• Records of material storage, handling, and use.
• Records of inspection of materials.
• Product inspection records.
• Testing records.

5.0 Process Control

The organization shall ensure the quality of products or services.

Guidance

“Process control” refers to the management of processes and procedures that affect the quality of products and services. Process control ensures that processes and procedures will be performed consistently and as they were intended to be performed. The program activities will include some or all of the following: procurement, preparation, processing, storage, and administration. To manage these activities, the program will develop and document processes and procedures that directly affect the quality of products and services.

In most programs, these processes and procedures will already exist, but they have to be identified and documented. When all processes and procedures conform to established requirements, their output should result in acceptable products and services.

To implement process control, programs may consider the following guidelines:

1. Identify the processes and procedures that need to be followed to fulfill the requirements for cellular therapy products.
2. Identify acceptable results or outcomes for the policies, processes, and procedures to evaluate whether they have been performed correctly.
3. Capture all processes and procedures in writing, as required in Standard 1.3.
4. Before implementation, validate all new processes and procedures to ensure they function as intended.
5. Review and approve processes and procedures, as required in Chapter 6, Documents and Records.
6. Monitor policies, processes, and procedures to ensure that identified outcomes are met, and redesign policies, processes, and/or procedures where needed.
7. Train staff to comply with processes and procedures, as required in Chapter 2, Resources.
8. Assess the competency of staff to perform procedures.
9. Validate equipment according to requirements outlined in Chapter 3, Equipment. (SS)

The ​committee revised standard 5.0 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Identify and document all processes and procedures affecting cellular therapy product quality.
  • Create a comprehensive list of processes and procedures.
  • Ensure documentation aligns with Standard 1.3 requirements.
• Define acceptable outcomes for each process and procedure.
  • Develop criteria to evaluate process performance.
• Validate all new processes and procedures prior to implementation.
  • Conduct validation studies and document results.
• Review and approve processes and procedures as per Chapter 6 requirements.
  • Maintain records of reviews and approvals.
• Monitor processes to ensure outcomes are met; redesign as necessary.
  • Implement a monitoring plan with defined metrics.
• Train staff on all processes and procedures.
  • Maintain training records and update as needed.
• Assess staff competency regularly.
  • Document competency evaluations and corrective actions.
• Validate equipment according to Chapter 3 requirements.
  • Keep equipment validation logs and maintenance records current.

5.1 General Elements

The organization shall ensure that processes are carried out under controlled conditions.

Guidance

Standard 5.1, General Elements, is a commonly cited standard for nonconformances. For example, nonconformances have been given when there is no documentation of the appearance or temperature acceptability for incoming products (Standard 5.8.1, #9). (SS)

☑ Actionable Checklist

• Develop and implement SOPs for monitoring and documenting controlled conditions for all processes.
  • Include procedures for verifying appearance and temperature of incoming products.
• Maintain a log for recording environmental conditions during processing.
• Conduct regular training sessions on process control SOPs and document attendance.
• Perform internal audits to ensure adherence to process control procedures.
• Review and update the Validation Master Plan (VMP) to include all critical processes.
• Document any deviations from controlled conditions and initiate CAPAs as necessary.

5.1.1 Change Control

[Cord blood applicable]

When the organization develops new processes or procedures or changes existing ones, they shall be validated before implementation.

Guidance

Standard 5.1.1 requires validation of new processes and procedures. When developing a new process, participation by representatives from all of the affected departments and work areas ensures that the planned activities fit and work within each environment. These same departments and work areas should then also participate in the validation of this new process.

To validate, perform the processes and procedures exactly as written in order to confirm that they work as expected. Validation confirms both of the following:

1. The plans on how to perform the work consistently achieve the intended results.
2. The work instructions are clear, complete, and easy to use.

Validation has to be performed before any new process or procedure is put into use to avoid implementing a flawed plan. Even when validation has been performed carefully, it is still possible to find errors and omissions after implementation. If errors occur, authorized and controlled changes to the way work is performed and to the corresponding processes and procedures need to be made without delay.

The intent of Standard 5.1.1 is not for programs to artificially perform validation on processes and procedures that have been in place for years. For these processes and procedures, retrospective validation is acceptable, which could include a review of historical records that serve as the documented evidence of a controlled process or procedure. The processes and procedures that are located in Chapter 5 are required to be controlled because they relate most directly to the quality of the facility’s products and services. When processes and procedures are validated and competent trained staff perform them the same way each time, the program can be confident that the controlled conditions will consistently result in the intended product.

Because CT Standards represents minimum requirements, facilities are encouraged to implement additional measures that are appropriate for their program. For example, facilities should consider validating safety processes, document control processes, ensure that the event reporting process works, or ensure that the competency assessment, internal audit tool, or any written procedure can be understood and executed. (SS)

The committee revised standard 5.1.1 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop a Change Control SOP outlining the process for validating new or modified procedures.
  • Include steps for involving representatives from all affected departments in the validation process.
• Create a Validation Plan template to document the validation process for each new or changed procedure.
  • Ensure the plan includes criteria for confirming intended results and clarity of work instructions.
• Perform validation of new or modified processes as per the Validation Plan before implementation.
  • Document results and any discrepancies found during validation.
• Maintain a Change Control Log to record all changes to processes and procedures.
  • Include details of validation activities and outcomes.
• Conduct retrospective validation for existing processes using historical records as evidence.
  • Document the review process and findings.
• Implement a training program to ensure staff are competent in performing validated processes consistently.

5.1.1.1

The facility shall identify the reasons for a change and obtain the appropriate approval(s) before implementation. Any changes that may affect the safety of the recipient or the identity, purity, potency, integrity, safety, or efficacy of the cellular therapy product shall be validated before the change is implemented. Standard 2.1.4 applies.

☑ Actionable Checklist

• Identify and document reasons for proposed changes using Change Control Form.
  • Ensure Change Control Form includes impact assessment on safety, identity, purity, potency, integrity, safety, or efficacy.
• Obtain necessary approvals from designated authority prior to change implementation.
• Validate changes that may affect critical attributes of the cellular therapy product.
  • Document validation results in the Validation Master Plan (VMP).
• Update relevant SOPs and training materials to reflect approved changes.
• Conduct training for affected staff on new procedures or changes.
• Maintain records of all change approvals, validations, and training in the quality management system.

5.1.2 Quality Control

[Cord blood applicable]

A program of quality control shall be established that is sufficiently comprehensive to ensure that
products, equipment, materials, and analytical functions perform as intended. Standard 1.2.2 applies.

Guidance

Standard 5.1.2, Quality Control, is a commonly cited standard for nonconformances. Examples of the reasoning behind the nonconformances include the following:

1. Quality control is not performed according to the facility’s SOPs.
2. Quality control material is not handled and tested according to the manufacturer’s instruction.
3. Quality control failures are not investigated.
4. Quality control is not reviewed. (SS)

The ​committee revised standard 5.1.2 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Establish and document a comprehensive Quality Control (QC) program in accordance with SOPs.
  • Review and update SOPs to ensure alignment with AABB Standard 5.1.2.
• Ensure all QC procedures are performed as outlined in the facility’s SOPs.
  • Conduct regular training sessions for staff on QC procedures.
• Handle and test QC materials according to the manufacturer’s instructions.
  • Maintain a log of all QC materials and their handling procedures.
• Investigate all QC failures promptly and document findings.
  • Implement corrective and preventive actions (CAPAs) for identified QC issues.
• Conduct regular reviews of QC activities and document outcomes.
  • Include QC reviews in management review meetings and document discussions.

5.1.2.1

Quality control results shall be reviewed and evaluated against acceptance criteria.

☑ Actionable Checklist

• Establish SOP for reviewing and evaluating quality control results.
  • Include criteria for acceptance and rejection in the SOP.
• Train staff on the SOP for quality control result evaluation.
  • Document training completion and competency evaluations.
• Implement a log or database for recording quality control results.
  • Ensure the log includes fields for acceptance criteria and evaluation outcomes.
• Schedule regular reviews of quality control results by qualified personnel.
  • Document each review and any actions taken in response to deviations.
• Conduct internal audits to verify adherence to the quality control review process.
• Include quality control result evaluations in management review meetings.
  • Document discussions and decisions related to quality control evaluations.

5.1.2.2

Quality control failures shall be investigated before release of test results, products, or services.

☑ Actionable Checklist

• Develop and implement an SOP for investigating quality control failures.
  • Include criteria for identifying and categorizing quality control failures.
  • Define roles and responsibilities for investigation team members.
• Maintain a log of all quality control failures and investigations.
• Ensure all investigations are documented using a standardized form.
• Conduct root cause analysis for each quality control failure.
• Implement corrective and preventive actions (CAPAs) based on investigation findings.
• Review and approve investigation reports before releasing test results, products, or services.

5.1.2.3

The validity of test results and methods and the acceptability of products or services provided shall be evaluated when quality control failures occur.

☑ Actionable Checklist

• Develop and implement an SOP for evaluating test results and methods when quality control failures occur.
  • Include criteria for identifying quality control failures.
  • Define procedures for investigating the root cause of failures.
• Maintain a log of all quality control failures and their evaluations.
• Conduct training sessions on the SOP for all relevant staff and document attendance.
• Perform regular audits to ensure compliance with the SOP and document findings.
• Review and update the SOP annually or as needed based on audit findings or process changes.
• Document corrective and preventive actions (CAPAs) taken in response to quality control failures.

5.1.2.4

Processing facilities shall prevent contamination of cellular therapy products; maintain the cellular therapy product’s identity, function, safety, purity and potency, and integrity; and prevent the transmission of infectious disease. This shall include:

1. Defining criteria for acceptable results of in-process tests and final cellular therapy product characteristics.
2. Monitoring and control of suitable process parameters and cellular therapy product characteristics.
3. Use of statistical techniques required for establishing, controlling, and verifying process requirements and product characteristics.

☑ Actionable Checklist

• Define and document criteria for acceptable results of in-process tests and final product characteristics in SOP CT-001.
• Implement a monitoring system for process parameters and product characteristics, using Form CT-002 for documentation.
• Conduct regular reviews of process monitoring data to ensure control and compliance with defined criteria.
• Utilize statistical techniques to establish, control, and verify process requirements, as outlined in SOP CT-003.
• Train staff on statistical methods and process control procedures, maintaining records in the Training Log CT-004.
• Perform internal audits to verify adherence to process control standards, documenting findings in Audit Report CT-005.

5.1.3 Process Planning

Quality requirements shall be incorporated into new or changed processes, products, services, and novel methods. Planning and implementation activities shall include the following:

1. Evaluation of accreditation, regulatory, and legal requirements related to the new or changed process, product, or service.
2. Review of current available knowledge (eg, review of medical practice and/or literature).
3. Evaluation of risk.* Standard 1.4 applies.
4. Identification of affected internal and external parties and mechanism to communicate relevant information.
5. Identification of performance measures applicable to the new or changed process, product, or service.
6. Evaluation of resource requirements.
7. Evaluation of the impact of the new or changed process, product, or service on other organization (or program) processes. Standards 2.1.3 and 10.0 apply.
8. Evaluation of the need to create or revise documents for the new or changed process, product, or service.
9. Review and approval of the output of process development and design activities (eg, pilot or scale-up study results, process flow charts, procedures, data forms).
10. Evaluation of the extent and scope of process validation or revalidation depending on the level of risk and impact of the new or changed products or services.

*21 CFR 1271.180.

Guidance

The committee added a crossreference to standard 1.4 to standard 5.1.3 subnumber 3 focused on risk assessment for completeness. The committee also added reference to the CFRs focused on general good tissue practices. (SC)

☑ Actionable Checklist

• Conduct a comprehensive review of accreditation, regulatory, and legal requirements for any new or changed process, product, or service.
  • Document findings in a regulatory compliance assessment report.
• Perform a literature review and consult current medical practices to gather knowledge relevant to the new or changed process.
  • Summarize findings in a knowledge review document.
• Conduct a risk assessment as per Standard 1.4 and 21 CFR 1271.180.
  • Document identified risks and mitigation strategies in a risk assessment log.
• Identify all internal and external parties affected by the change and establish a communication plan.
  • Maintain a communication log to track information dissemination.
• Define and document performance measures applicable to the new or changed process.
  • Include performance measures in the process validation plan.
• Assess resource requirements for implementing the new or changed process.
  • Document resource needs in a resource allocation plan.
• Evaluate the impact of the new or changed process on existing organizational processes.
  • Document findings in a process impact analysis report.
• Determine the need for creating or revising documents related to the new or changed process.
  • Update or create SOPs, forms, and logs as necessary.
• Review and approve outputs from process development and design activities.
  • Document approvals in a process development review log.
• Evaluate the need for process validation or revalidation based on risk and impact.
  • Document validation requirements in the Validation Master Plan (VMP).

5.1.4 Process Validation

Before implementation, the new or changed processes and procedures shall be validated.

Guidance

Validation should be performed in-house. For example, another department within a facility could validate a computer system so long as validation activities are designed to ensure that the computer system operates as intended in the environment in which it will be used by the relevant staff. However, a validation of the computer system performed off-site by a vendor would not meet this standard. (SS)

The committee revised standard 5.1.4 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop and document a Validation Master Plan (VMP) for all new or changed processes.
  • Include specific validation protocols and acceptance criteria.
• Conduct in-house validation studies for new or changed processes.
  • Ensure validation activities are performed in the actual environment of use.
• Assign a qualified team to perform validation activities, ensuring independence from process owners.
• Document all validation activities, results, and conclusions in a validation report.
• Review and approve validation reports by the quality management team before process implementation.
• Update relevant SOPs and training materials to reflect validated processes.

5.1.4.1

Validation activities shall include the following:

1. Identification of objectives, individual(s) responsible, expected outcomes, and/or performance measures.
2. Criteria for review of outcomes.
3.  Approval of validation plan.
4. Review and approval of actual results.
5. Actions to be taken if objectives are not met.

Standards 2.1.3 and 2.1.4 apply.

Guidance

The committee revised standard 5.1.4.1 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Identify and document validation objectives, responsible personnel, expected outcomes, and performance measures in the Validation Master Plan (VMP).
  • Review and update the VMP to ensure all objectives and responsibilities are clearly defined.
• Establish and document criteria for reviewing validation outcomes in relevant SOPs.
• Obtain documented approval of the validation plan from authorized personnel prior to implementation.
• Conduct a review of actual validation results and obtain documented approval from authorized personnel.
• Develop and document a corrective action plan in SOPs for instances where validation objectives are not met.
• Ensure compliance with Standards 2.1.3 and 2.1.4 by cross-referencing relevant SOPs and documentation.

5.1.5 Process Implementation

The implementation of new or changed processes and procedures shall be planned and controlled.

☑ Actionable Checklist

• Develop and document a detailed implementation plan for new or changed processes.
  • Include timelines, responsible personnel, and resources required in the plan.
• Conduct a risk assessment for the new or changed process.
  • Document identified risks and mitigation strategies.
• Update or create SOPs to reflect the new or changed processes.
  • Ensure SOPs are reviewed and approved prior to implementation.
• Train all relevant personnel on the new or changed processes.
  • Document training sessions and maintain training records.
• Validate the new or changed processes to ensure they meet intended outcomes.
  • Record validation results and any deviations encountered.
• Monitor the implementation and effectiveness of the new or changed processes.
  • Conduct a follow-up review and document findings in a management review report.

5.1.5.1

Postimplementation evaluations of new or changed processes and procedures shall be performed.

☑ Actionable Checklist

• Develop an SOP for conducting postimplementation evaluations of new or changed processes.
  • Include criteria for evaluation, responsible personnel, and timeline.
• Maintain a log of all new or changed processes and procedures.
• Schedule and document postimplementation evaluations within 30 days of process change.
• Use a standardized form to record findings from postimplementation evaluations.
• Review evaluation results in management review meetings and document any required actions.
• Implement CAPAs for any identified issues during the evaluations and document their effectiveness.

5.1.6 Use of Materials

All materials shall be stored and used in accordance with the manufacturer’s written instructions and shall meet specified requirements.

Guidance

The committee added new standard 5.1.8 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Verify that all materials used are stored according to the manufacturer’s instructions.
  • Maintain a log of storage conditions for all materials.
• Ensure all materials meet specified requirements before use.
  • Document verification of material specifications in a materials acceptance log.
• Develop and maintain SOPs for the storage and use of materials.
  • Review and update SOPs annually or as needed.
• Train staff on proper storage and use of materials according to SOPs.
  • Keep training records and competency evaluations up to date.
• Conduct regular audits to ensure compliance with manufacturer instructions and specified requirements.
  • Document findings and corrective actions in audit reports.

5.1.7 Inspection

The organization shall ensure that products or services are inspected at organization-defined stages.

Guidance

The committee added new standard 5.1.7 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Define and document specific stages for product or service inspection in an SOP.
  • Include criteria for inspection at each stage.
• Train staff on inspection procedures and document training records.
• Implement an inspection log to record findings at each defined stage.
• Conduct regular audits to ensure compliance with inspection procedures.
• Review and update inspection criteria annually or as needed.
• Document any deviations found during inspections and initiate CAPAs.

5.1.8 Identification and Traceability

[Cord blood applicable]

The organization shall ensure that all products or services are identified and traceable.

Guidance

The committee added new standard 5.1.8 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for product identification and traceability.
  • Include procedures for labeling, documentation, and tracking of all products.
• Maintain a traceability log for all cord blood products.
• Conduct regular audits to verify the accuracy and completeness of traceability records.
• Train staff on identification and traceability procedures and document training records.
• Implement a system for tracking deviations and CAPAs related to traceability.
• Review and update the traceability process annually or as needed.

5.1.9 Handling, Storage, and Transportation

The organization shall ensure that products or services are handled, stored, and transported in a manner that prevents damage, limits deterioration, and provides traceability.*

*21 CFR 1271.290.

Guidance

The committee added new standard 5.1.8 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop and implement SOPs for handling, storage, and transportation of products to prevent damage and deterioration.
  • Reference SOP-001: Product Handling Procedures.
  • Reference SOP-002: Storage Conditions and Monitoring.
  • Reference SOP-003: Transportation Protocols.
• Ensure all storage areas are equipped with temperature and humidity monitoring devices.
  • Maintain calibration logs for monitoring devices.
• Train staff on handling, storage, and transportation SOPs, and document training records.
• Conduct regular audits to verify compliance with handling, storage, and transportation procedures.
• Implement a traceability system for all products during handling, storage, and transportation.
  • Use Form-101: Product Traceability Log.
• Document and review any deviations or incidents related to handling, storage, and transportation, and implement CAPAs as needed.

5.1.9.1

[Cord blood applicable]

The facility shall ensure that suppliers and/ or consignees of cellular therapy products provide evidence of processes for traceability, tracking, and recall of products. Standard 7.2.5 applies.

Guidance

The intent of the standard is to ensure that there is appropriate documentation to allow for the reliable tracking of products that move between facilities and the ability to recall products if needed. Examples of documentation of a facility’s process may include SOPs, audit reports verifying compliance with procedures, or traceability logs. (SS)

The committee created new standard 5.1.9.1 to ensure that suppliers provide evidence of traceability of product to the facility they have agreements with. (SC)

5.1.9.1.1

[F]

The facility shall have a policy for the use/issue of a cellular therapy product provided by a supplier and/or received by a consignee that lacks a complete chain of custody. Standards 7.2.4 and 7.2.6.2 apply.

Guidance

If a product lacks complete chain of custody documentation, the administering facility should have a documented process for release of the product. Documentation should provide evidence of product identity, purity, potency, safety, and/or efficacy.

Examples of records that may be used when complete chain of custody is not available include:

• Certificate of analysis.
• Product record review summary, with identification of the individual performing the review and inclusion of any quality events (deviations, product holds, quarantines, out-of-specification notices).
• Associated product records, including labeling, integrity documentation, sterility testing, cell enumeration, and viability testing. (SS)

​The committee created new standard 5.1.9.1.1 for completeness. This standard recognizes that there are instances where a provider of a product may not have complete chain of custody and that their use is approved knowing this information. (SC)

☑ Actionable Checklist

• Develop and implement SOPs for ensuring traceability, tracking, and recall of cellular therapy products from suppliers and consignees.
  • Include procedures for verifying supplier documentation of traceability processes.
  • Outline steps for tracking product movement between facilities.
  • Define recall procedures for products if necessary.
• Conduct regular audits of supplier compliance with traceability and tracking procedures.
  • Document audit findings and corrective actions taken.
• Maintain traceability logs for all cellular therapy products received and distributed.
  • Ensure logs are updated in real-time and reviewed periodically.
• Establish a policy for handling cellular therapy products with incomplete chain of custody documentation.
  • Include criteria for product release based on identity, purity, potency, safety, and efficacy.
• Keep records of Certificates of Analysis and product record review summaries for products with incomplete documentation.
  • Document any quality events such as deviations, product holds, or quarantines.
• Ensure all associated product records, including labeling and testing results, are complete and accessible.

5.1.10 Proficiency Testing

[Cord blood applicable]

The facility shall participate in an external proficiency testing program for each analyte measured
by the laboratory. Proficiency testing for each analyte shall be performed at least twice a year.

☑ Actionable Checklist

• Identify all analytes measured by the laboratory and document them in a proficiency testing log.
  • Update the proficiency testing log biannually with results and corrective actions.
• Enroll in an external proficiency testing program for each identified analyte.
  • Verify enrollment confirmation and maintain records in the proficiency testing file.
• Schedule proficiency testing for each analyte at least twice a year.
  • Document testing dates and results in the proficiency testing log.
• Review proficiency testing results with laboratory staff and document findings.
  • Implement corrective actions for any deficiencies and record in the CAPA log.
• Include proficiency testing results in the management review agenda.
• Update relevant SOPs to reflect proficiency testing requirements and procedures.

5.1.10.1

For each analyte requiring proficiency testing under Clinical Laboratory Improvement
Amendments (CLIA),* each laboratory shall participate in a Centers for Medicare and
Medicaid Services (CMS)-approved proficiency testing program.

*42 CFR 493.801.

5.1.10.1.1

Laboratories shall ensure that no interlaboratory communications pertaining to proficiency test events occur until after the submission deadline.^†

^† 42 CFR 493.801(b)(4).
For accredited facilities that are assessed by AABB for CLIA conformance, refer to the Verification of CLIA Compliance Form before on-site assessment.

Guidance

The purpose of this requirement is for facilities that have multiple laboratories participating in the same proficiency testing events to ensure that no results or communication sharing occurs between the multiple laboratories within the same organization for proficiency testing events until after each of the laboratories has submitted their individual proficiency testing results for grading. Such communications are permissible after the date the test results are due to the proficiency testing program. (SS)

The committee created new standard 5.1.10.1.1 for completeness. The standard ensures that the IRL Standards mirror the requirements set forth by CMS in July 2022 with an effective date of 2024. This mostly focuses on wave testing, which is not performed by our laboratories, however the requirement does focus on proficiency testing referrals and what is and is not allowed until the results of proficiency testing is complete and submitted. (SC)

5.1.10.1.2

The laboratory shall ensure that no portion of a proficiency testing sample is sent to another laboratory for analysis.*

*42 CFR 493.801(b)(5).
For accredited facilities that are assessed by AABB for CLIA conformance, refer to the Verification of CLIA Compliance Form before on-site assessment.

Guidance

Laboratories that refer portions of their patient/donor testing, including reflex or confirmatory testing, to other laboratories (including interorganizational laboratories) for analysis need to have a process preventing proficiency testing samples from such referral. Laboratories should perform and report only on proficiency samples for the testing that they typically perform. Any additional testing that should be performed by another laboratory should not be included. (SS)

The committee created new standard 5.1.10.1.2 for completeness. This addition was made in conjunction with the addition of the CFR cited, which requires that laboratories that perform proficiency testing show that they can successfully perform the act. Laboratories that attempt to have their samples outsourced would not meet the requirements in the CFR. (SC)

5.1.10.1.3

Any laboratory that receives a proficiency testing sample from another laboratory shall notify CMS of the receipt of the sample.^†

^†42 CFR 493.801(b)(4).
For accredited facilities that are assessed by AABB for CLIA conformance, refer to the  Verification of CLIA Compliance Form before on-site assessment.

Guidance

The purpose of proficiency testing is to obtain an external and independent assessment of a facility’s performance by evaluating its laboratory’s performance against preestablished criteria. By assessing the actual results produced by the laboratory, proficiency testing reflects on all aspects of the laboratory’s quality assurance system. To send the proficiency testing out to another laboratory for analysis or to perform analysis on another laboratory’s proficiency testing sample(s) defeats the purpose of the proficiency testing and is a violation of CMS regulations in 42 CFR 493.801(b)(4). Laboratories should not report proficiency testing results for tests that they do not normally perform. Most forms for reporting proficiency testing outcomes have an area to indicate if any part of the testing is not routinely performed in the laboratory or if it is normally referenced out to another facility for completion. This standard also ensures that laboratories have a process to escalate these findings to the appropriate entity. (SS)

☑ Actionable Checklist

• Enroll in a CMS-approved proficiency testing program for each required analyte.
  • Maintain documentation of enrollment and participation in the proficiency testing program.
• Implement a policy prohibiting interlaboratory communication about proficiency test events until after submission deadlines.
  • Train all laboratory staff on this policy and document the training.
• Ensure no portion of proficiency testing samples is sent to another laboratory for analysis.
  • Review and update SOPs to reflect this requirement.
• Use the Verification of CLIA Compliance Form before on-site assessments to ensure adherence to CLIA requirements.
• Conduct internal audits to verify compliance with proficiency testing requirements and document findings.
• Maintain records of all proficiency testing results and corrective actions taken for any non-conformances.

5.1.10.2

In the absence of an approved external proficiency testing program, proficiency testing
shall include comparison of test results from an outside laboratory.

☑ Actionable Checklist

• Identify and document external laboratories for test result comparison.
  • Maintain a list of approved external laboratories in the SOP.
• Develop and implement an SOP for proficiency testing without an external program.
• Schedule regular proficiency testing intervals and document in a testing log.
• Compare test results with external laboratories and document findings.
  • Use a standardized form for documenting comparison results.
• Review and analyze discrepancies in test results with external laboratories.
  • Document corrective actions in a CAPA log if discrepancies are found.
• Include proficiency testing results in management review meetings.

5.1.10.3

[Cord blood applicable]

Proficiency testing results shall be reviewed by the medical or laboratory director or designee.^‡

^‡42 CFR 493.1236.
For accredited facilities that are assessed by AABB for CLIA conformance, refer to the Verification of CLIA Compliance Form before on-site assessment.

Guidance

The committee added new standard 5.1.10.1.3 to the edition for completeness. This addition was made in conjunction with the addition of the CFR cited, which requires that if a laboratory receives samples for proficiency testing from an outside source that they immediately contact CMS who will instruct them on how to move forward. (SC)

5.1.10.3.1

Proficiency testing shall be successful. Failures shall be investigated and corrective actions taken, including notification to potentially impacted parties and appropriate regulatory bodies, as applicable.^§ Standard 1.4 applies.

^§42 CFR 493.803 and 42 CFR 493.1236(b).
For accredited facilities that are assessed by AABB for CLIA conformance, refer to the Verification of CLIA Compliance Form before on-site assessment.

Guidance

Proficiency testing determines the performance of individual laboratories for specific tests or measurements and is used to monitor laboratories’ continuing performance.

Facilities that perform tests required by these CT Standards should enroll in an external proficiency test program for each analyte tested. In such programs, the laboratory is sent samples that are then tested using standard practices. The results are reported back to the external program and typically graded based on accuracy either related to a reference value or in peer comparison.

In the event of an unsuccessful proficiency test, records of donor/patient testing and quality control that occurred around the time of proficiency testing failure should also be reviewed to ensure that testing was not affected by this occurrence.

This review should include donor or patient testing and quality control records review for a sufficient period of time before and after the proficiency testing failure was discovered to detect any negative impacts or deterioration in performance. (SS)

The committee added the clause, “…including notification to potentially impacted parties and appropriate regulatory bodies, as applicable.” for clarity. The expansion ensures that all individuals that need to be contacted in the case of a failure are notified. (SC)

☑ Actionable Checklist

• Ensure proficiency testing results are reviewed by the medical or laboratory director or designee.
  • Document the review process in the Proficiency Testing Review SOP.
• Maintain a Verification of CLIA Compliance Form for on-site assessments.
• Enroll in an external proficiency test program for each analyte tested.
• Investigate any proficiency testing failures and document findings in the Proficiency Testing Investigation Log.
  • Implement corrective actions and document them in the CAPA Log.
  • Notify potentially impacted parties and regulatory bodies as applicable.
• Review donor/patient testing and quality control records around the time of proficiency testing failures.
  • Document the review process in the Quality Control Review Log.

5.2 Outcome Data

[F]

The facilities shall have a program to obtain, audit, and monitor clinical outcomes of cellular therapy products at defined intervals. Standard 5.28 applies.

Guidance

Clinical outcomes assessment can be performed in collaboration with the clinical facility. Facilities may want to develop policies or plans (eg, a safety outcome monitoring and analysis plan) describing audit criteria by which to assess reported outcome data, such as septic transfusion reactions. Facilities should trend their data over time to detect opportunities for improvement or the need to increase the frequency of monitoring.

Agreements that include requirements for communication of clinical outcomes should be in place per Standard 4.2.3.2, including sub-Standard 4.2.3.2.3. For collections that are performed by contracted procurement facilities for further manufacturing, there should be agreements that include requirements for communication of adverse outcomes related to donor safety and the procurement process. For processing facilities, there shall be an agreement to communicate with the manufacturer about events that may have impacted the quality of the product. However, the contracted manufacturer or party holding licensure may not be under contractual obligation to communicate to a procurement and/or processing facility the clinical outcomes of administration of a product unless the responsible party’s investigation suggests that an element of the procurement or processing phase was a contributing factor. (SS)

☑ Actionable Checklist

• Develop and implement a program to obtain, audit, and monitor clinical outcomes of cellular therapy products at defined intervals.
  • Create SOP for outcome data collection and monitoring.
  • Define specific intervals for data collection and review.
• Establish agreements with clinical facilities for communication of clinical outcomes.
  • Ensure agreements include requirements for reporting adverse outcomes.
  • Review agreements regularly to ensure compliance with Standard 4.2.3.2.
• Develop a safety outcome monitoring and analysis plan.
  • Define audit criteria for assessing reported outcome data.
  • Include criteria for septic transfusion reactions and other adverse events.
• Trend outcome data over time to identify opportunities for improvement.
  • Utilize data trending tools and software for analysis.
  • Schedule regular reviews of trended data to inform process improvements.
• Document all findings, deviations, and corrective actions in quality records.
  • Ensure all CAPAs are tracked and closed in a timely manner.
  • Conduct management reviews of outcome data and CAPAs.

5.2.1

For the procurement and processing facilities, this shall include, but is not limited to, adverse events and complications attributed to procurement, processing, infusion, and/or engraftment, as applicable.

☑ Actionable Checklist

• Develop and implement an SOP for documenting and investigating adverse events and complications.
  • Include specific procedures for procurement, processing, infusion, and engraftment.
• Maintain an adverse event log with detailed records of each incident.
• Conduct regular training sessions on adverse event identification and reporting for all relevant staff.
• Perform root cause analysis for each adverse event and document findings.
• Implement CAPAs for identified issues and track their effectiveness.
• Review and update the SOP annually or after significant changes in processes.

5.2.2

For the clinical facility, this shall include the clinical outcomes as specified by the clinical protocols and as applicable:

1. Mortality and survival rates.
2. Disease status and/or relapse.
3. Adverse events and complications.
4. Disease-modifying activity.
5. Engraftment.
6. Immune effector cell endpoints.
7. Hematopoietic reconstitution.
8. Monitoring of patient safety.

Guidance

Facilities may want to develop audit criteria by which to assess their outcome data. Facilities should trend their data over time to detect opportunities for improvement or the need to increase the frequency of monitoring.

For the procurement and processing facilities, clinical outcomes assessment can be performed in collaboration with the clinical facility. Septic transfusion reactions are an example of a clinical outcome that might be attributed to procurement and/or processing. Facilities may want to develop audit criteria by which to assess their outcome data.

Facilities should trend their data over time to detect opportunities for improvement or the need to
increase the frequency of monitoring. (SS)

☑ Actionable Checklist

• Develop and implement SOPs for tracking clinical outcomes as specified by clinical protocols.
  • Include mortality and survival rates, disease status, and adverse events.
  • Document disease-modifying activity and engraftment outcomes.
  • Record immune effector cell endpoints and hematopoietic reconstitution.
• Establish a system for monitoring patient safety, including adverse events and complications.
• Create audit criteria to assess outcome data and identify trends over time.
• Collaborate with procurement and processing facilities to assess clinical outcomes.
• Conduct regular reviews of outcome data to identify opportunities for improvement.
• Maintain records of all outcome assessments and reviews for compliance verification.

5.2.2.1

The clinical facility shall determine the criteria for cellular therapy product safety, product
efficacy, and/or clinical outcome data and collect these data for analysis at defined intervals.

Guidance

Standard 5.2.2.1 requires that there be a system to identify, monitor, and analyze outcome data.

One way to meet the intent of this standard would be for facilities to develop audit criteria by which to assess their outcome data. Two examples of key performance indicators to track and trend are timely engraftment of neutrophils and platelets. Facilities should track their data over a defined interval, for example, quarterly or biannually, to detect opportunities for improvement or the need to increase the frequency of monitoring. Reporting of key performance indicators and/or clinical outcomes will be designated to a responsible person(s) (see Standard 1.2.1). “Monitoring” refers to observing and recording data and subsequently determining the impact on a facility. Monitoring the data and trends enables early detection of events that may lead to adverse events and the development of process improvement initiatives.

Expectations for sharing and analyzing data between facilities should be in accordance with agreements made between parties. For the procurement and processing facilities, clinical outcomes assessment can be performed in collaboration with the clinical facility. Septic transfusion reactions are an example of a clinical outcome that might be attributed to procurement and/or processing. (SS)

☑ Actionable Checklist

• Develop and document criteria for cellular therapy product safety, efficacy, and clinical outcomes in an SOP.
  • Include key performance indicators such as timely engraftment of neutrophils and platelets.
• Establish a schedule for collecting and analyzing outcome data at defined intervals (e.g., quarterly or biannually).
• Assign responsibility for data collection, analysis, and reporting to designated personnel as per SOP.
• Implement a system for monitoring and recording outcome data, ensuring data integrity and accuracy.
• Conduct regular audits of outcome data to identify trends and opportunities for improvement.
• Establish agreements with collaborating facilities for data sharing and analysis, ensuring compliance with all relevant standards.

5.2.3

For facilities that procure, process, or administer investigational products, there shall be a process for recording and monitoring patient safety and reviewing clinical outcomes as specified by the independent-ethics-committee-approved protocol(s).

Guidance

The processing facility should consider working closely with the clinical group to outline the parameters of recipient safety and clinical outcomes to be monitored and reported. The parameters for safety of the recipient should include review of product sterility and endotoxin, while those for clinical outcomes should include any adverse events in the peritransplant and immediate posttransplant period that might be associated with, for example, the islet cell administration.

Parameters such as changes in exogenous insulin requirements should be considered as well. Reduction in exogenous insulin requirements reflects islet cell graft function, while insulin independence is almostalways associated with the loss of serious hypoglycemia. Although successful islet transplantation should have a major impact on quality of life, measuring the perceived positive and negative outcomes of the transplantation regimen is quite complex. Existing quantitative instruments should be used when available. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for recording and monitoring patient safety and clinical outcomes as per protocol.
  • Include parameters for product sterility and endotoxin levels.
  • Define adverse event reporting procedures for peritransplant and posttransplant periods.
• Collaborate with the clinical team to outline specific safety and outcome parameters.
  • Document roles and responsibilities in a cross-functional team agreement.
• Establish a system for tracking changes in exogenous insulin requirements.
  • Use validated quantitative instruments for measuring clinical outcomes.
• Conduct regular reviews of patient safety data and clinical outcomes.
  • Schedule and document management reviews of monitoring results.
• Maintain a log of all investigational product administrations and associated outcomes.
• Ensure all staff involved in the process are trained and competency evaluated on relevant SOPs.

5.2.4

The sharing and review of data shall be defined. Standard 4.2.5 and Chapter 7, Deviations, Nonconformances, and Adverse Events, apply.

☑ Actionable Checklist

• Define and document procedures for sharing and reviewing process control data in SOP-5.2.4.
  • Include roles and responsibilities for data sharing in the SOP.
• Establish a schedule for regular review meetings to discuss process control data.
  • Document meeting minutes and action items in Meeting Log-5.2.4.
• Cross-reference SOP-5.2.4 with SOP-4.2.5 to ensure alignment with data sharing requirements.
• Integrate process control data review into the Deviation and Nonconformance Management system.
  • Use Form-7.1 for documenting any deviations or nonconformances identified during data reviews.
• Train relevant staff on SOP-5.2.4 and maintain training records in Training Log-5.2.4.
• Conduct internal audits to verify compliance with SOP-5.2.4 and document findings in Audit Report-5.2.4.

5.2.4.1

[F]

There shall be defined processes and procedures for the issuing facility and/or product
manufacturer to obtain information on adverse events and patient outcomes appropriate for each cell type.

Guidance

For example, for hematopoietic transplants in the United States, data would be reported to the contract holder for the Stem Cell Therapeutic Outcomes Database of the CW Bill Young Program of the Center for International Blood and Marrow Transplant Research (CIBMTR) outcome registry. For cellular therapies under investigational use, outcome data should be reported to the agency overseeing the treatment protocol or clinical trial. (SS)

☑ Actionable Checklist

• Develop and document SOPs for obtaining information on adverse events and patient outcomes for each cell type.
  • Include specific procedures for hematopoietic transplants and investigational cellular therapies.
• Establish a communication protocol with the issuing facility or product manufacturer to report adverse events.
• Create a log or database to record all adverse events and patient outcomes, ensuring traceability and compliance.
• Train staff on the procedures for reporting and documenting adverse events and outcomes.
• Schedule regular reviews of adverse event reports and patient outcomes to identify trends and areas for improvement.
• Ensure all reports are submitted to the appropriate registry or oversight agency, such as CIBMTR, in a timely manner.

5.3 Materials Management

[Cord blood applicable]

There shall be policies, processes, and procedures for the qualification, receipt, handling, quarantine, storage, and utilization of all materials used in the procurement, processing,
and administration of cellular therapy products. Critical materials shall be identified and traceable.

Guidance

The committee has added the term “quarantine” to standard 5.3 for completeness. This addition represents the current practice in the field. (SC)

☑ Actionable Checklist

• Develop and maintain SOPs for the qualification, receipt, handling, quarantine, storage, and utilization of materials.
  • Include criteria for identifying critical materials and ensuring their traceability.
• Implement a material quarantine process to isolate non-qualified materials until approval.
• Maintain a log for tracking the receipt and qualification status of all materials.
• Conduct regular audits to verify compliance with material management SOPs.
• Ensure all staff involved in materials management are trained and competency evaluated.
• Document all deviations and CAPAs related to materials management processes.

5.3.1

All critical materials, including containers and solutions used for collection, processing, preservation, and storage of cellular therapy products, and all reagents used for tests, shall be stored and used in accordance with the manufacturer’s written instructions and shall meet specified requirements.

☑ Actionable Checklist

• Verify that all critical materials have current manufacturer instructions on file.
  • Ensure storage conditions are documented and align with manufacturer specifications.
• Implement an SOP for the receipt, storage, and handling of critical materials.
• Maintain a log for tracking the lot numbers and expiration dates of all critical materials.
• Conduct regular audits to confirm compliance with manufacturer instructions.
• Document any deviations from manufacturer instructions and initiate CAPA as needed.
• Train staff on the proper storage and handling procedures for critical materials.

5.3.2 Receipt of Materials

The facility shall ensure that incoming materials that come into contact with the patient or cellular therapy product or that directly affect the quality of a cellular therapy product are not used until they have been inspected or otherwise verified as conforming to requirements. Standard 4.8 applies.

☑ Actionable Checklist

• Develop and implement an SOP for the inspection and verification of incoming materials.
  • Include criteria for acceptance and rejection of materials.
  • Define roles and responsibilities for personnel involved in the inspection process.
• Maintain a log for recording the receipt and inspection results of all incoming materials.
  • Include fields for date of receipt, material description, inspection outcome, and inspector’s signature.
• Train relevant staff on the SOP for receipt and inspection of materials.
  • Document training completion and maintain records in the training log.
• Establish a quarantine area for materials pending inspection and verification.
  • Ensure materials are clearly labeled as “Pending Inspection” until verified.
• Conduct regular internal audits to ensure compliance with the SOP for receipt of materials.
  • Document findings and implement corrective actions for any identified non-conformities.
• Review and update the SOP for receipt and inspection of materials annually or as needed.
  • Document any changes and communicate updates to all relevant staff.

5.3.2.1 Quarantine of Critical Materials

[Cord blood applicable]

The facility shall establish a process for quarantine and disposition of critical supplies and materials.

Guidance

Refer to the glossary for how “critical materials” are defined. A facility should have a process that ensures critical materials are verified as suitable before use. Further, the facility should have a policy that outlines actions to take when materials meet or fail to meet the defined criteria. (SS)

The committee created new standard 5.3.2.1 focused on quarantine for completeness. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for the quarantine of critical materials, including criteria for quarantine and release.
  • Define “critical materials” in the SOP based on the glossary.
  • Include steps for verifying suitability of materials before use.
• Establish a log or database to track the status of quarantined materials.
  • Record the date, reason for quarantine, and disposition decision.
• Train relevant staff on the quarantine process and document completion of training.
• Conduct regular audits to ensure compliance with the quarantine SOP.
• Create a policy outlining actions for materials that fail to meet criteria, including corrective actions.
• Review and update the quarantine process annually or as needed based on audit findings.

5.3.2.2

[Cord blood applicable]

Records of the following shall be maintained:

1. Identification of the material.
2. Name of the manufacturer.
3. Lot number.
4. Date of receipt.
5. Date of manufacture and/or expiration date.
6. Results of visual inspection upon receipt, if applicable.
7. Identity of the person receiving the material, if applicable.
8. Indication of acceptance or rejection.
9. Identity of the person determining acceptance or rejection of the material.
10. Certificate of analysis, manufacturer’s insert, or equivalent, if applicable.
11. Quantity.

☑ Actionable Checklist

• Develop and maintain an SOP for recording material identification, including specific fields for each required data point.
  • Include fields for manufacturer name, lot number, and quantity.
• Implement a log or electronic system to capture and store the date of receipt and expiration/manufacture dates.
• Train staff on visual inspection procedures and ensure results are documented upon receipt.
• Designate personnel responsible for receiving materials and ensure their identity is recorded.
• Establish a process for documenting acceptance or rejection of materials, including the identity of the decision-maker.
• Maintain a file or database for certificates of analysis, manufacturer’s inserts, or equivalent documents.
• Conduct regular audits to ensure all records are complete and accurate, referencing SOPs and logs.

5.3.2.3 Emergency Use of Material

[Cord blood applicable]

When a material is used on an emergency basis (before final acceptance), the material shall be identified to permit recall and quarantine of associated products. Standard 7.1 applies.

☑ Actionable Checklist

• Develop and implement an SOP for emergency use of materials, including identification and tracking processes.
  • Ensure the SOP includes steps for labeling materials used in emergencies to enable recall and quarantine.
• Maintain a log of all materials used on an emergency basis, including details necessary for traceability.
• Train staff on procedures for emergency use of materials, emphasizing identification and recall processes.
• Conduct regular audits to ensure compliance with emergency use SOP and traceability requirements.
• Review and update the SOP and training materials annually or after any emergency use incident.
• Document all incidents of emergency use, including actions taken for recall and quarantine, in a deviation report.

5.3.3 Qualification of Critical Materials

Materials that come into contact with the patient or cellular therapy product shall be sterile and of
appropriate grade for the intended use and shall be approved for human use by the US FDA or relevant Competent Authority. Standard 4.2 applies.

☑ Actionable Checklist

• Verify that all materials in contact with patients or products are sterile and approved for human use by the FDA or relevant authority.
  • Maintain a list of all critical materials and their qualification status.
  • Ensure documentation of FDA or Competent Authority approval for each material.
• Develop and implement SOPs for the qualification of critical materials.
  • Include procedures for initial qualification and requalification.
• Conduct regular audits to ensure compliance with material qualification requirements.
  • Document findings and corrective actions in audit reports.
• Maintain records of material lot numbers, certificates of analysis, and sterility documentation.
• Train staff on the importance of using qualified materials and document training sessions.

5.3.3.1

Materials that are not approved for human use by the FDA or relevant Competent Authority shall be qualified on the basis of one or more of the following criteria:

1. Medical literature supporting the use of the material for the specified purpose.
2. Approval by the facility’s independent ethics committee.
3. Investigational new drug (IND) or device approval for the specific material and indication, as permitted by the FDA or relevant Competent Authority.

Guidance

A facility cannot use local outcome/engraftment data to support the use of non-FDA-approved solutions for stem cell processing when there are alternatives available. If the facility can produce published data in a peer-reviewed journal specifically supporting the use of these reagents in stem cell processing, then these conditions may satisfy the intent of the standard if the outcomes are similar to those using FDA approved materials. A protocol approved by an IRB and/or an FDA-approved IND application or other exception as permitted by the FDA would also serve to meet these requirements. Additionally, it would be recommended that the facility support its claims that engraftment/outcome data are comparable to data obtained using FDA-approved reagents. This can be demonstrated by performing a retrospective validation of engraftment/outcome data at the facility and showing comparability. (SS)

5.3.3.1.1

The facility shall perform testing to ensure suitability of the material for its intended use.

Guidance

Materials shall be tested using the procedure that will be used at the facility. For example, freezing materials must be tested using the freezing procedure in place at the facility. If this procedure changes, then retesting should occur. (SS)

5.3.3.1.2

The facility shall qualify, verify, and validate critical materials for their intended use.

Guidance

The committee created new standard 5.3.3.1.2 for completeness. This concept is in place in current medical practice. (SC)

☑ Actionable Checklist

• Compile and review medical literature supporting the use of non-FDA-approved materials for specified purposes.
  • Document findings and maintain a literature review log.
• Obtain approval from the facility’s independent ethics committee for the use of non-FDA-approved materials.
  • Record meeting minutes and approval documentation.
• Secure IND or device approval for specific materials and indications from the FDA or relevant Competent Authority.
  • Maintain copies of all IND applications and approvals.
• Perform testing to ensure the suitability of materials for their intended use.
  • Use the facility’s current procedures for testing.
  • Document all test results in a validation report.
• Qualify, verify, and validate critical materials for their intended use.
  • Update the Validation Master Plan to include new materials.
  • Archive all qualification and validation records.
• Conduct retrospective validation of engraftment/outcome data to demonstrate comparability with FDA-approved reagents.
  • Document the validation process and results in a report.

5.3.4

[Cord blood applicable]

Reagents prepared in-house shall be produced using a validated method. Such reagents shall be inspected before release. Standards 5.3.2.2, 5.3.5, and 5.3.6 apply.

Guidance

Refer to the glossary for how a “reagent” is defined. For example, an in-house reagent would include:

1. Colony-forming units (CFUs) or other culture media prepared from raw materials.
2. Preparation of physiologic buffers and wash solutions for cultured mesenchymal stem cells (MSCs). (SS)

☑ Actionable Checklist

• Develop and document a validated method for the preparation of in-house reagents in an SOP.
  • Include detailed procedures for preparing CFUs, culture media, physiologic buffers, and wash solutions.
• Implement a system for inspecting in-house prepared reagents before release.
  • Use a standardized inspection form to record inspection results.
• Conduct a gap analysis against standards 5.3.2.2, 5.3.5, and 5.3.6 to ensure compliance.
• Maintain a log of all prepared reagents, including batch numbers, preparation dates, and inspection outcomes.
• Train relevant staff on the SOP for reagent preparation and inspection.
  • Keep training records and competency evaluations up to date.
• Schedule regular internal audits to verify adherence to the validated method and inspection process.

5.3.5 Utilization

[Cord blood applicable]

Non-single-use materials that come into contact with the patient or cellular therapy products during procurement, processing, or administration shall be cleaned and sterilized. Sterilization methods shall be validated and monitored, according to specified requirements.

Guidance

The committee added the clause, “according to specified requirements…” to ensure that the methods used are in accordance with defined requirements specific to the product in use. (SC)

☑ Actionable Checklist

• Develop and maintain an SOP for cleaning and sterilizing non-single-use materials.
  • Include validation and monitoring procedures for sterilization methods.
• Validate sterilization methods according to product-specific requirements.
  • Document validation results and maintain records.
• Implement a monitoring system for sterilization processes.
  • Record and review sterilization logs regularly.
• Train all relevant staff on the SOP and sterilization procedures.
  • Maintain training records and competency evaluations.
• Conduct regular internal audits to ensure compliance with sterilization SOPs.
  • Document audit findings and implement corrective actions as needed.
• Review and update the SOP annually or as needed based on changes in standards or processes.

5.3.6

[F]

Use of critical materials shall be recorded in a manner that ensures complete and accurate traceability of any given cellular therapy product to all critical materials that come into contact with the patient or cellular therapy product. Chapter 7, Deviations, Nonconformances, and Adverse Events, applies.

☑ Actionable Checklist

• Implement a traceability SOP for recording the use of all critical materials.
  • Include procedures for documenting lot numbers, expiration dates, and supplier details.
• Maintain a traceability log for each cellular therapy product.
  • Ensure the log includes all critical materials used during processing.
• Conduct regular audits of traceability records to ensure completeness and accuracy.
• Train staff on traceability procedures and document training records.
• Review and update traceability procedures annually or as needed.
• Document any deviations or nonconformances related to traceability and implement CAPAs.

5.3.6.1

[Cord blood applicable]

For all critical materials used, records of the following shall be retained:

1. The manufacturer’s package insert, if applicable.
2. Certificates of analysis or equivalent, as defined by the facility’s qualification program.
3. Any manufacturer’s documentation, including recall or defect notices, advisories, and other communications related to material usage.

Guidance

If a facility intends to use online package inserts, the facility should have a process for the retention and review of these records. Either electronic or hard copies of the package inserts should be accessible. (SS)

☑ Actionable Checklist

• Retain the manufacturer’s package insert for all critical materials in either electronic or hard copy format.
  • Ensure accessibility of package inserts, whether stored online or physically.
• Maintain certificates of analysis or equivalent documentation as per the facility’s qualification program.
• Document and retain any manufacturer’s communications, including recall or defect notices and advisories.
• Develop and implement an SOP for the retention and review of online package inserts.
• Conduct regular audits to verify the completeness and accessibility of records for critical materials.
• Update the crosswalk document to map SOPs related to critical material record retention to AABB Standard 5.3.6.1.

5.4 Methods and Operational Controls

☑ Actionable Checklist

• Develop and maintain SOPs for all critical processes, ensuring alignment with AABB standards.
  • Review and update SOPs annually or as needed based on process changes.
• Implement a Validation Master Plan (VMP) for all critical processes.
  • Document validation protocols and results for each process.
• Conduct regular internal audits to ensure compliance with process controls.
  • Use the AABB Assessment Tool to identify gaps and areas for improvement.
• Maintain a crosswalk document mapping SOPs to AABB and FACT-JACIE standards.
• Keep training records and competency evaluations current for all staff involved in critical processes.
• Document all process deviations and implement corrective and preventive actions (CAPAs).
  • Review CAPAs during management reviews to ensure effectiveness.

5.4.1 Cellular Therapy Product Manipulation

Cellular therapy product manipulation shall address the following:

1. Staff attire, gowning, and use of personal protective equipment.
2. Use of biological safety cabinets or other environmentally controlled spaces, if applicable.
3. Materials and equipment for each specific process.
4. Manipulation of materials.
5. Critical calculations.
6. Transfer of source material, cellular therapy products, media, or reagents between containers.
7. Sampling of source material, cellular therapy products, media, reagents, or other materials used in product manipulation.
8. Acceptable control limits for temperature, humidity, and gases such as oxygen and carbon dioxide, if applicable.
9. Disposition of cellular therapy by-products and waste.
10. Labeling.

Guidance

Maintaining acceptable levels of temperature and humidity is important during storage of supplies and reagents, as well as adhering to requirements established by the manufacturer for use of supplies, reagents, and equipment. A product container, for example, may require certain temperature and humidity levels in order to provide proper gas exchange and maintain the proper environment for the cells stored within the container.

A piece of equipment, particularly anything electrical or electronic, may give erroneous results or
become unsafe for the user when environmental conditions are outside of the manufacturer’s requirements for use. Environmental limits should be determined according to what the supplies, reagents, and equipment would tolerate. These can be very difficult to control, depending on a facility’s geographic location. Limits established should be broad enough to anticipate expected variations but still be within acceptable ranges. Use of a humidifier or dehumidifier may be necessary to control humidity. There may be danger of electrical shock if a piece of equipment is in use when humidity is above the recommended range. Personnel should read package inserts for storage specifications of supplies and reagents and review operating manuals for each piece of equipment used in the laboratory. Environmental controls must also be taken into consideration when purchasing new equipment. (SS)

The committee added “Labeling” as new #10 to standard 5.4.1, #10 for completeness. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for staff attire, gowning, and use of personal protective equipment specific to cellular therapy product manipulation.
• Ensure the use of biological safety cabinets or other environmentally controlled spaces is documented and validated, if applicable.
• Maintain an inventory log of materials and equipment used for each specific process, ensuring they meet manufacturer specifications.
• Create an SOP detailing the manipulation of materials, including handling procedures and safety measures.
• Validate and document all critical calculations, ensuring accuracy and compliance with standard protocols.
• Establish and document procedures for the transfer of source material, cellular therapy products, media, or reagents between containers.
• Implement a sampling log for source material, cellular therapy products, media, reagents, or other materials used in product manipulation.
• Monitor and document acceptable control limits for temperature, humidity, and gases such as oxygen and carbon dioxide, if applicable.
• Develop a waste management SOP for the disposition of cellular therapy by-products and waste.
• Ensure all labeling complies with regulatory requirements and is documented in the labeling SOP.

5.4.2 Aseptic Methods

Procurement, processing, and clinical facilities shall establish and maintain policies, processes, and procedures designed to minimize contamination of the product and infection of the donor or recipient.
The following shall be addressed:

1. Environmental controls and monitoring commensurate with the risk of product contamination.
2. Process controls.
3. Staff training in aseptic technique.
4. Attire, gowning, and use of personal protective equipment.
5. Workflow and movement of personnel through workspaces.
6. Sterilization of equipment, as applicable.

Guidance

The committee added “Sterilization of equipment, as applicable” as new subnumber 6 to standard 5.4.2 ensuring that sterilization is a part of aseptic methods. (SC)

☑ Actionable Checklist

• Develop and implement SOPs for environmental controls and monitoring specific to each processing area.
  • Establish a schedule for regular environmental monitoring and document results.
  • Review and update environmental control SOPs annually or as needed.
• Create process control SOPs to ensure consistent application of aseptic methods.
  • Validate process controls through regular audits and document findings.
• Conduct initial and annual refresher training for staff on aseptic techniques.
  • Maintain training records and competency evaluations for all staff.
• Implement SOPs for attire, gowning, and use of personal protective equipment (PPE).
  • Conduct regular audits to ensure compliance with gowning and PPE protocols.
• Design and document workflow and personnel movement plans to minimize contamination risks.
  • Review and adjust workflow plans based on audit findings or process changes.
• Establish and maintain SOPs for the sterilization of equipment, where applicable.
  • Validate sterilization processes and maintain logs of sterilization activities.

5.4.2.1

[Cord blood applicable]

The effectiveness of such measures shall be monitored and reviewed at defined intervals. Chapter 7, Deviations, Nonconformances, and Adverse Events, applies.

☑ Actionable Checklist

• Establish a schedule for regular monitoring and review of process control measures.
  • Document the schedule in the Quality Management Plan (QMP).
• Develop and implement SOPs for monitoring process control effectiveness.
  • Reference SOPs in the Process Control Log.
• Conduct periodic reviews of process control data and document findings.
  • Use the Process Control Review Form for documentation.
• Integrate findings from process control reviews into the management review process.
  • Update the Management Review Minutes with relevant findings.
• Ensure all deviations, nonconformances, and adverse events are documented and analyzed.
  • Maintain a Deviations and Nonconformances Log.
• Implement corrective and preventive actions (CAPAs) based on review outcomes.
  • Track CAPA implementation in the CAPA Tracking Log.

5.4.3 Operational Controls

[Cord blood applicable]

Operational controls shall prevent mix-ups and contamination. The following shall be defined:

1. Movement and storage of materials (including waste) and equipment within workspaces.
2. Physical and/or temporal segregation of equipment or materials.
3. Physical and/or temporal segregation for processing different cellular therapy products or cellular therapy product lots.
4. Physical and/or temporal segregation of cellular therapy products determined to be nonconforming or where donor eligibility has not been determined or the donor is ineligible.
5. Use and storage of materials that may adversely affect the quality of the cellular therapy product.
6. Cleaning and setup of spaces and equipment between production runs.
7. Labeling processes.
8. Clerical identification checks at critical steps.

Chapter 7, Deviations, Nonconformances, and Adverse Events, applies.

Guidance

The committee added “Physical and/or temporal segregation of cellular therapy products determined to be nonconforming or where donor eligibility has not been determined or the donor is ineligible” as new subnumber 4 to standard 5.4.3, to ensure that the standards remain in conformance with FDA regulations. The requirement should be in place with accredited institutions currently. (SC)

☑ Actionable Checklist

• Develop and implement SOPs for the movement and storage of materials, including waste, within workspaces.
  • Include procedures for equipment movement and storage.
• Establish protocols for physical and/or temporal segregation of equipment or materials.
  • Define criteria for segregation during processing of different cellular therapy products or lots.
• Implement procedures for segregation of nonconforming cellular therapy products or those with undetermined/ineligible donor status.
  • Ensure clear labeling and separate storage areas for these products.
• Create SOPs for the use and storage of materials that could affect cellular therapy product quality.
  • Regularly review and update the list of such materials.
• Define cleaning and setup procedures for spaces and equipment between production runs.
  • Document cleaning logs and verify completion before new runs.
• Develop and enforce labeling processes to prevent mix-ups.
  • Include clerical identification checks at critical steps in the process.
• Conduct regular training and competency evaluations for staff on operational controls.
  • Maintain records of training and evaluations.

5.4.4 Irradiation and Leukocyte Reduction

Policies, processes, and procedures shall be in place regarding irradiation or leukocyte reduction of cellular therapy products.

Guidance

Facility policies should clearly list the instances when irradiation and/or leukocyte reduction is or is not performed. Irradiation and leukocyte reduction are not often performed on cell therapy products; however, given the significant implications of inappropriate procedures, facilities should evaluate the need for irradiation and leukocyte reduction for all their products. (SS)

☑ Actionable Checklist

• Develop and document a policy outlining when irradiation and leukocyte reduction are required for cellular therapy products.
  • Include criteria for determining necessity based on product type and patient needs.
• Create SOPs for performing irradiation and leukocyte reduction, ensuring alignment with regulatory requirements.
  • Reference specific equipment and methods used in the procedures.
• Implement a training program for staff on the policies and procedures for irradiation and leukocyte reduction.
  • Maintain training records and competency evaluations for all relevant personnel.
• Establish a log to document each instance of irradiation and leukocyte reduction, including date, product details, and personnel involved.
• Conduct regular audits to ensure compliance with the established policies and procedures for irradiation and leukocyte reduction.
• Review and update the policies and procedures annually or as needed based on new evidence or regulatory changes.

5.4.4.1

Methods shall be in place to prevent unintentional irradiation or leukocyte reduction
(eg, filtration) of cellular therapy products. Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products, applies.

☑ Actionable Checklist

• Develop and implement an SOP for handling and labeling cellular therapy products to prevent unintentional irradiation or leukocyte reduction.
  • Include specific steps for verifying product labels before processing.
  • Ensure SOP references Reference Standard 5.6.2A for labeling requirements.
• Train all relevant staff on the SOP and document completion of training.
• Conduct regular audits to verify compliance with the SOP and document findings.
• Maintain a log of all cellular therapy products processed, including checks for proper labeling.
• Implement a system for double-checking product labels before any processing step.
• Review and update the SOP annually or as needed based on audit findings or process changes.

5.5 Product Identification and Traceability

The facility shall maintain the chain of identity and chain of custody for identification and traceability of each cellular therapy product and all related samples from their initial source, through all processing and testing steps, to their final disposition. Policies, processes, and procedures shall also allow the identification and traceability of each cellular therapy product and all related samples from their final disposition, through all processing and/or testing steps, back to their source.

☑ Actionable Checklist

• Develop and maintain SOPs for product identification and traceability covering all stages from source to final disposition.
  • Include procedures for labeling, documentation, and record-keeping in the SOPs.
• Implement a tracking system to log each cellular therapy product and related samples at every processing and testing step.
  • Ensure the system is regularly updated and audited for accuracy.
• Train staff on the identification and traceability procedures and document all training sessions.
• Conduct regular audits to verify compliance with traceability requirements and document findings.
• Maintain a log of all chain of custody records for each product and sample.
• Establish a CAPA process for addressing any deviations in product identification and traceability.

5.5.1 Traceability and Unique Identification

[Cord blood applicable]

A numeric or alphanumeric system shall be used that will make it possible to trace any cellular therapy product or sample from donor/source to recipient/final disposition and back to the donor/source and to review records applying to the specific cellular therapy product or sample, including those related to reported adverse events. Unique identifiers shall not be obscured, altered, or removed.

☑ Actionable Checklist

• Implement a numeric or alphanumeric system for unique identification of all cellular therapy products and samples.
  • Ensure the system allows tracing from donor/source to recipient/final disposition and vice versa.
• Develop and maintain SOPs for assigning and managing unique identifiers.
  • Include procedures for ensuring identifiers are not obscured, altered, or removed.
• Conduct regular audits to verify traceability from donor/source to recipient and back.
• Train staff on the importance and procedures of maintaining unique identifiers.
  • Document all training sessions and retain records.
• Implement a system for documenting and reviewing records related to adverse events.
  • Ensure these records are linked to the unique identifiers of the products involved.

5.5.1.1 Unique Identification of Intermediate Facility

If an intermediate facility assigns a local, unique, numeric, or alphanumeric identification to the cellular therapy product, the label shall be affixed to the cellular therapy product and shall identify the facility assigning the identification and shall be traceable to the original cellular therapy product.

Guidance

The unique number that is on the product at distribution may not be “obscured, altered, or removed.” However, the facility may have removed the unique number that was on the product when it was received and placed a new label on that product with the unique identifier the facility assigned to it. This is fine as long as it is “traceable to the original cellular therapy product” and meets all other labeling requirements. This new unique identifier the facility assigned should not be “obscured, altered, or removed” while under its control. For example, there could be a record that links the original unique identifier to the unique identifier the facility assigns. All other labeling requirements must be met, and the length of storage for retaining the linking information must be met as well.

For partial labels, refer to the labeling chart (Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products) for the minimal information that must be on the product; the unique identifier must be one of those labeling items. Again, it can be the unique identifier the facility assigned, as long as its records can always link its unique identifier to the unique identifier(s) that was assigned to that cell therapy product. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for assigning unique identifiers to cellular therapy products.
  • Ensure the SOP includes steps for affixing labels with unique identifiers.
  • Include procedures for maintaining traceability to the original product.
• Create a log or database to record the linkage between original and facility-assigned unique identifiers.
  • Ensure the log is updated in real-time and regularly audited for accuracy.
• Train staff on the SOP for labeling and traceability of cellular therapy products.
  • Document all training sessions and maintain records.
• Conduct regular internal audits to verify compliance with labeling and traceability requirements.
  • Use audit findings to implement corrective actions if necessary.
• Review and update the Validation Master Plan (VMP) to include validation of the labeling process.
• Ensure that all labels meet the requirements outlined in Reference Standard 5.6.2A for minimal information.

5.5.1.2 Special Requirements for Pooled Cellular Therapy Products or Combined Products

Where pooling or combining of cellular therapy products is permissible, there shall be a
procedure to ensure traceability of all cellular therapy products in a pool, and the (quantitative) contribution of each product to the final cellular therapy product.* Standard 1.4 applies.

*21 CFR 1271.220(b).

☑ Actionable Checklist

• Develop and implement an SOP for pooling or combining cellular therapy products, ensuring traceability and quantitative contribution tracking.
  • Include detailed steps for documenting the source and quantity of each product in the pool.
  • Reference 21 CFR 1271.220(b) within the SOP for regulatory compliance.
• Create a traceability log to record the details of each cellular therapy product included in the pool.
  • Ensure the log captures donor ID, product ID, and quantitative contribution.
• Train staff on the new SOP and traceability log, documenting all training sessions and competency evaluations.
• Perform regular internal audits to verify adherence to the pooling SOP and traceability requirements.
• Review and update the Validation Master Plan (VMP) to include validation of the pooling process.
• Document any deviations or CAPAs related to pooling activities, and review them in management meetings.

5.5.1.3 Sample Traceability

Samples from donors, products, and recipients shall be labeled in a manner to ensure traceability of the sample to its source.

☑ Actionable Checklist

• Develop and implement an SOP for labeling samples to ensure traceability to the source.
  • Include procedures for labeling donor, product, and recipient samples.
• Use a standardized labeling system with unique identifiers for each sample.
• Train staff on the sample labeling SOP and document the training.
• Conduct regular audits of sample labeling practices to ensure compliance.
• Maintain a log of all labeled samples, including source information and unique identifiers.
• Review and update the labeling SOP annually or as needed to address any identified gaps.

5.6 Labels, Labeling, and Labeling Controls

[Cord blood applicable]

The facility shall have policies, processes, and procedures for labels and labeling of products and samples.* At a minimum, they shall address:

1. The acquisition and creation of cellular therapy product label templates.
2. Verification that the label stock meets facility-defined specifications.
3. The qualification, review, and approval of labels before use. Standard 6.1.2 applies.
4. The controls in place to ensure proper cellular therapy product identification.
5. The control of label inventory and templates, including discard. Chapter 6, Documents and Records, applies.

Standards 1.1.2 and 5.10.10 apply.

*21 CFR 1271.10(a)(2).
FDA Guidance: Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use (July 21, 2020).

Guidance

Items 1 through 5 in Standard 5.6 list elements that should be considered as part of labeling controls:

1. How the label templates will be acquired and created.
2. How the label stock will be verified to meet facility-defined specifications.
3. How the labels will be qualified, reviewed, and approved before use.
4. What controls are in place to ensure proper identification of cell therapy products.
5. How label inventory and templates are controlled, including discard of labels.

This standard is also a commonly cited standard for nonconformances when there is no process for reconciliation and traceability of labels from production to destruction. (SS)

☑ Actionable Checklist

• Develop and document SOPs for the acquisition and creation of cellular therapy product label templates.
  • Include steps for design, approval, and version control of label templates.
• Establish a verification process to ensure label stock meets facility-defined specifications.
  • Maintain records of label stock specifications and verification results.
• Implement a qualification, review, and approval process for labels before use.
  • Reference SOP 6.1.2 for label approval procedures.
• Define and document controls to ensure proper cellular therapy product identification.
  • Conduct regular audits to verify adherence to identification controls.
• Create and maintain a system for the control of label inventory and templates, including discard procedures.
  • Ensure compliance with Chapter 6, Documents and Records, for label inventory management.
• Document all deviations and CAPAs related to labeling processes and conduct regular management reviews.

5.6.1

[Cord blood applicable]

Cellular therapy products shall be labeled in conformance with the current versions of ISBT 128^† or Eurocode labeling. Standard 5.5 applies.

^†www.isbt128.org.

Guidance

AABB has required cell therapy facilities to use the ISBT 128 or Eurocode product nomenclature and to have implemented ISBT 128 or Eurocode labeling.

Facilities that collect cellular therapy products by apheresis that are for further manufacturing by a clinical trial sponsor or manufacturer should follow the manufacturer’s labeling requirements as approved by the entity that approved the licensed product (or regulated investigational product) or adopt the standardized labeling as per ICCBBA Standard ST-018, Labeling of Collection Products for Cellular Therapy Manufacturing, and should include a sponsor/manufacturer-
assigned unique identifier, a unique code used to discern a cell or gene therapy and the intended
therapy recipient, on the label to maintain the chain of identity. (SS)

☑ Actionable Checklist

• Implement ISBT 128 or Eurocode labeling for all cellular therapy products.
  • Update SOPs to include ISBT 128 or Eurocode labeling requirements.
  • Train staff on the ISBT 128 or Eurocode labeling process and document training.
• Conduct a gap analysis to ensure compliance with ISBT 128 or Eurocode labeling standards.
• Verify that all labels include a unique identifier for chain of identity maintenance.
• Regularly audit labeling processes to ensure ongoing compliance with ISBT 128 or Eurocode standards.
• Document any deviations in labeling and implement CAPAs as necessary.

5.6.1.1 Label Terminology

Product names, attributes, and descriptions on product labels shall use the terms and
definitions found in the Standard Terminology for Medical Products of Human Origin^‡ or terminology consistent with Eurocode labeling terminology.

^‡www.isbt128.org/standard-terminology.

☑ Actionable Checklist

• Review all product labels to ensure they use terms from the Standard Terminology for Medical Products of Human Origin or Eurocode labeling terminology.
  • Cross-reference each label term with the ISBT 128 standard terminology list.
• Update SOPs related to labeling (e.g., SOP-Label-001) to include references to the required terminology standards.
• Conduct training sessions for staff on the importance of using standardized terminology in labeling.
  • Document attendance and comprehension in training records.
• Perform a quarterly audit of product labels to verify compliance with the terminology standards.
  • Record findings and corrective actions in the audit log.
• Implement a change control process for any updates to labeling terminology, ensuring alignment with the latest standards.
• Maintain a log of any deviations related to labeling terminology and document CAPAs in the deviation management system.

5.6.1.2

Apheresis and marrow products shall be labeled with ISBT 128 or Eurocode labels at the time of procurement.

5.6.1.2.1

Other cellular therapy products shall be labeled with the proper product name and a unique alpha or numeric identifier at the time of procurement.

Guidance

For products other than apheresis and marrow, there may be situations (eg, cord blood collections) in which it is not feasible to label a product at procurement with a full ISBT 128 label. It is the expectation that the minimum information for a partial or reduced label will be a unique identifier and the name of the product that will be collected. In addition, a full ISBT label should be applied at the earliest point possible thereafter. Standard 5.6.1.2 applies. (SS)

☑ Actionable Checklist

• Implement SOP for labeling apheresis and marrow products with ISBT 128 or Eurocode at procurement.
  • Train staff on SOP and document training records.
  • Conduct regular audits to ensure compliance with labeling SOP.
• Develop SOP for labeling other cellular therapy products with a unique identifier and product name at procurement.
  • Include procedures for applying a full ISBT 128 label as soon as feasible.
• Maintain a log of all labeled products, including unique identifiers and product names.
• Perform a gap analysis to ensure all labeling practices meet AABB and FACT-JACIE standards.
• Review and update labeling SOPs annually or as needed based on regulatory changes.
• Document all deviations from labeling procedures and implement CAPAs as necessary.

5.6.1.3

Cellular therapy products shall be labeled with ISBT 128 or Eurocode labels at the completion of processing.

☑ Actionable Checklist

• Verify that all cellular therapy products are labeled with ISBT 128 or Eurocode labels post-processing.
  • Conduct a monthly audit of product labels to ensure compliance.
• Update SOPs to include steps for labeling with ISBT 128 or Eurocode at the completion of processing.
• Train staff on the labeling process and document completion in training records.
• Maintain a log of all labeled products, including date and personnel responsible.
• Review and update the Validation Master Plan to include label validation processes.
• Implement a CAPA process for any deviations related to labeling errors.

5.6.1.4

The facility shall have policies to address emerging labeling standards and ensure action is taken, as applicable.

Guidance

Facilities are expected to stay current with ISBT 128 or Eurocode labeling standards. The intent of this standard is to ensure that when new labeling standards are introduced, facilities have a process that outlines how to determine if updated standards are relevant to the facility and what actions to take. (SS)

The committee created new standard 5.6.1.4 to ensure that accredited facilities have plans in place to recognize and address new labeling requirements as appropriate. (SC)

☑ Actionable Checklist

• Develop and maintain a policy for monitoring updates to ISBT 128 and Eurocode labeling standards.
  • Assign responsibility for monitoring labeling standard updates to a designated staff member.
• Implement a procedure to evaluate the relevance of new labeling standards to the facility.
  • Document the evaluation process and criteria used to determine applicability.
• Update SOPs and training materials to reflect any changes in labeling standards.
  • Ensure all relevant staff are trained on updated labeling procedures.
• Conduct an internal audit to verify compliance with current labeling standards.
• Maintain records of all evaluations, decisions, and actions taken regarding labeling standard updates.

5.6.1.5

The receiving facility shall have a process in place for the traceability of products labeled in a different system or version.

Guidance

The facility should perform a review of all processes and procedures to ensure that accuracy and completeness of labeling information are verified at specific intervals. The facility will place a new label on the product with a unique identifier that is traceable to the original cell therapy product and meets all other labeling requirements of ISBT 128 and Eurocode labeling. The facility shall have policies, processes, and procedures for labeling and labeling control. Facilities that collect cellular therapy products by apheresis that are for further manufacturing by a clinical trial sponsor or manufacturer should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product. For further information, refer to the guidance associated with Standards 5.8 and 6.2.2. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for the traceability of products labeled in different systems or versions.
  • Include procedures for verifying accuracy and completeness of labeling information.
  • Ensure the SOP aligns with ISBT 128 and Eurocode labeling requirements.
• Establish a process to place a new label with a unique identifier on products, ensuring traceability to the original product.
• Conduct regular reviews of labeling processes and procedures to ensure compliance and accuracy.
• Maintain a chain of custody log for cellular therapy products, ensuring it is concurrent, permanent, and auditable.
• Train staff on the new labeling and traceability procedures, documenting all training sessions and competency evaluations.
• Perform internal audits to verify adherence to the labeling SOP and traceability processes, documenting findings and corrective actions.

5.6.2

All containers of source materials, in-process cellular therapy products, and final products shall be labeled in accordance with Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products, and Reference Standard 5.6.2B, Requirements for Labeling Shipping Containers.

☑ Actionable Checklist

• Review and update SOP for labeling cellular therapy products to ensure compliance with Reference Standard 5.6.2A and 5.6.2B.
  • Include specific label content requirements for source materials, in-process, and final products.
  • Detail procedures for labeling shipping containers.
• Conduct training sessions for staff on updated labeling procedures and document attendance.
• Implement a labeling checklist to verify compliance with labeling requirements before product release.
• Perform regular audits of labeled products and shipping containers to ensure adherence to standards.
• Document any labeling deviations and initiate CAPAs as necessary.
• Maintain a log of all labeling-related deviations and corrective actions taken.

5.6.2.1

Regulated investigational products shall be labeled according to local and/or FDA or relevant Competent Authority regulations.

☑ Actionable Checklist

• Review and update SOPs for labeling investigational products to align with local and FDA regulations.
  • Ensure SOPs include specific labeling requirements for investigational products.
• Conduct a gap analysis of current labeling practices against FDA and local regulations.
• Implement a labeling checklist to verify compliance before product release.
• Train staff on labeling requirements for investigational products.
  • Document all training sessions and maintain records.
• Perform regular audits of labeling processes and records.
• Establish a CAPA process for addressing any labeling deviations.

5.6.2.2

Products approved or licensed by the applicable local authority and/or the FDA or relevant Competent Authority shall be labeled according to the terms of licensure or approval.

Guidance

The requirements for labeling do not preempt federal, state, and/or local laws and regulations.

For licensed products, if an ISBT 128 label is not required by the regulatory agency that approved the product (or regulated investigational product), then the labeling required by the licensing (or investigational product) entity supersedes the requirement for ISBT 128 labeling, and Standard 5.6.2.2 applies.

Facilities may review Reference Standard 5.6.2A to ensure the labeling elements are either on the label provided by the manufacturer or are available in the records and accompanying documents, in order to meet the intent of Standard 5.6.2.

If the final product label, approved by the regulatory agency that approved the product (or regulated investigational product), does not conform to these labeling standards, one way to meet the intent of the standard would be for the facility to present evidence that the final label was submitted and approved prior to distribution of the final product.

Of note, Standard 5.1.2.2 refers to Standard 5.5, whose substandards pertain to traceability. Thus, a receiving or administering facility of a product will need to make sure it has clearly documented traceability for a non-ISBT-128-labeled product. Facilities receiving or administering labeled products should make sure they “have a process in place for the traceability of products labeled in a different system or version,” as noted in Standard 5.6.1.5, one of the substandards of 5.6.1, which is referenced in footnote 3 of Reference Standard 5.6.2A. (SS)

☑ Actionable Checklist

• Verify that all products are labeled according to the terms of licensure or approval by the applicable local authority or FDA.
  • Review and document the labeling requirements specified by the licensing or investigational product entity.
• Ensure that the labeling elements required by Reference Standard 5.6.2A are present on the product label or in accompanying documents.
• Maintain records of the final product label approval from the regulatory agency prior to distribution.
• Develop and implement a process for traceability of products labeled in a non-ISBT-128 system.
  • Document traceability procedures in SOPs and ensure staff are trained on these procedures.
• Conduct regular audits to ensure compliance with labeling and traceability requirements.
• Keep records of any deviations from labeling standards and implement corrective actions as needed.

5.6.3 Labeling

[Cord blood applicable]

Labeling information shall be verified for accuracy and completeness.

☑ Actionable Checklist

• Develop and implement an SOP for labeling verification processes.
  • Include steps for double-checking label information against source documents.
• Train staff on the labeling SOP and document completion in training records.
• Conduct regular audits of labeling processes to ensure compliance and document findings.
• Maintain a log of all labeling verifications, including date, personnel, and outcomes.
• Implement a CAPA process for addressing any labeling discrepancies identified.
• Review and update the labeling SOP annually or as needed based on audit findings.

5.6.3.1

The procurement facility shall verify labeling immediately after procurement.

☑ Actionable Checklist

• Develop and implement an SOP for verifying labeling immediately after procurement.
  • Include steps for checking label accuracy, completeness, and legibility.
• Train staff on the labeling verification process and document training records.
• Use a standardized labeling verification checklist during the procurement process.
• Maintain a log of all labeling verifications conducted, including date, time, and personnel involved.
• Conduct regular audits of labeling verification records to ensure compliance.
• Implement a CAPA process for any labeling discrepancies identified during verification.

5.6.3.2

The processing and/or storage facility shall verify labeling at the following times, at a
minimum:

1. Upon receipt at the processing and/or storage facility.
2. At facility-defined in-process steps, including transfer to a different storage location and removal/retrieval of attached segments and/or samples, if applicable.
3. At completion of processing and/or before storage.
4. Before distribution or issue.

☑ Actionable Checklist

• Develop and implement an SOP for label verification upon receipt at the processing and/or storage facility.
  • Include a checklist for verifying label accuracy and completeness.
• Define and document in-process steps requiring label verification, including transfer to different storage locations and removal of segments/samples.
  • Update SOPs to include these steps and associated label verification procedures.
• Create a procedure for label verification at the completion of processing and/or before storage.
  • Ensure the procedure includes a verification log for recording outcomes.
• Establish a protocol for label verification before distribution or issue.
  • Maintain a distribution log with a section for label verification confirmation.
• Train staff on all label verification procedures and maintain training records.
• Conduct regular audits to ensure compliance with label verification procedures and document findings.

5.6.3.3

The administering facility shall verify labeling before administration of the cellular therapy product.

☑ Actionable Checklist

• Develop and implement an SOP for verifying labeling of cellular therapy products before administration.
  • Include steps for double-checking patient identifiers and product details.
• Train all relevant staff on the labeling verification SOP and document training completion.
• Create a labeling verification checklist form to be completed before product administration.
• Conduct regular audits of labeling verification processes and document findings.
• Maintain records of all labeling verifications performed, including any discrepancies and corrective actions taken.
• Review and update the labeling verification SOP annually or as needed based on audit findings and regulatory changes.

5.6.4

Cellular therapy products for investigational use or approved for use by the FDA or relevant Component Authority shall be labeled according to protocol, and all elements required shall be included in the accompanying records or be readily available. Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products, applies.

Guidance

The labeling on cellular therapy products for investigational use or approved by the FDA or relevant Competent Authority should be reviewed and approved. The Competent Authorities for both the originating and destination facilities should be considered. If labeling elements required by these standards are not on the label, they should be readily available in accompanying records; they are not required to be affixed or attached to the product(s). (SS)

☑ Actionable Checklist

• Develop and maintain an SOP for labeling cellular therapy products, referencing protocol and regulatory requirements.
  • Include steps for label creation, review, and approval by authorized personnel.
• Implement a checklist for verifying that all required labeling elements are included or available in accompanying records.
• Conduct regular audits of labeling processes to ensure compliance with Reference Standard 5.6.2A.
• Train staff on labeling requirements and document all training sessions and competency evaluations.
• Maintain a log of all labels used, including version control and approval records.
• Review and update labeling SOPs and checklists annually or as regulations change.

5.7 Transport and Shipping

[Cord blood applicable]

The facility shall limit deterioration, prevent damage, ensure timely delivery, and protect the quality of the materials and cellular therapy products during transport and shipping while maintaining chain of custody and chain of identity.*

*21 CFR 1271.265.

Guidance

Maintaining CT products within a specified range of temperature is critical to the viability and potency of the cells. The ideal temperature for storage and transportation may vary based on the type of product.

The standards require that facilities establish and maintain policies, processes, and procedures to store, transport, and ship products at temperature ranges that are acceptable for the specific product and that they monitor and track these temperatures during transport and shipping. This includes validating the shipping containers used for transport to ensure that they maintain products at the acceptable temperature range. In addition, the facility’s policies should be agreed to and complied with by outside facilities that collect, process, and/or ship products to the facility. It does not matter if no adverse trends have been noted, because absence of a known problem is insufficient for compliance with these CT Standards. (SS)

☑ Actionable Checklist

• Develop and implement SOPs for the transport and shipping of cellular therapy products, including temperature control and chain of custody.
  • Include specific temperature ranges for each product type in the SOPs.
• Validate and document the performance of shipping containers to ensure they maintain required temperature ranges.
  • Conduct periodic re-validation of shipping containers and document results.
• Establish agreements with external facilities on transport and shipping procedures, including temperature monitoring and chain of identity.
  • Review and update agreements annually or as needed.
• Implement a system for monitoring and documenting temperatures during transport and shipping.
  • Use temperature logs or electronic monitoring systems to record data.
• Conduct regular audits of transport and shipping processes to ensure compliance with SOPs and standards.
  • Document findings and corrective actions from audits.
• Train staff on transport and shipping SOPs, including temperature monitoring and chain of custody procedures.
  • Maintain training records and competency evaluations for all relevant personnel.

5.7.1

The facility shall control packaging to ensure conformance with specified requirements. Local, FDA or relevant Competent Authority, and/or international transport/shipping regulations apply.

☑ Actionable Checklist

• Develop and maintain an SOP for packaging control that includes compliance with local, FDA, and international regulations.
  • Review and update the SOP annually or as regulations change.
• Implement a packaging checklist to verify conformance with specified requirements before shipment.
• Train staff on packaging SOPs and document training records.
• Conduct regular audits of packaging processes to ensure compliance with SOPs.
• Maintain a log of all packaging materials used, including lot numbers and expiration dates.
• Document and review any deviations or non-conformances in packaging processes and implement CAPAs as needed.

5.7.2

[Cord blood applicable]

Shipping or transport containers shall be qualified at defined intervals to ensure that they maintain temperatures within the acceptable range for the expected duration of transport or shipping.

☑ Actionable Checklist

• Develop and implement SOP for qualification of shipping containers.
  • Include criteria for acceptable temperature ranges and duration.
• Schedule and conduct regular qualification tests for all shipping containers.
  • Document results in a qualification log.
• Review and update qualification intervals based on historical data and risk assessment.
• Maintain records of all shipping container qualifications and re-qualifications.
• Train staff on SOP and procedures for container qualification.
  • Keep training records and competency evaluations up to date.
• Perform internal audits to ensure compliance with shipping container qualification SOP.

5.7.3

[F]

When products are transported or shipped, the extent of temperature monitoring shall be defined and shall be appropriate to the duration of transport or shipping.

☑ Actionable Checklist

• Define temperature monitoring requirements in SOP for all transport/shipping scenarios.
  • Include specific temperature ranges and acceptable limits.
  • Specify duration thresholds for monitoring adjustments.
• Validate temperature monitoring devices for accuracy and reliability.
• Implement a log system to record temperature data during transport/shipping.
• Train staff on procedures for temperature monitoring and documentation.
• Conduct regular audits of temperature monitoring records for compliance.
• Document any deviations from defined temperature ranges and initiate CAPAs as needed.

5.7.3.1

[F]

When cryopreserved products are shipped, the temperature of the shipping container shall be continuously monitored.

Guidance

Whether or not this standard applies often relies on the definition of “shipping.” For example, a facility may say that they do not ship cryopreserved cell therapy products but use a liquid nitrogen (LN2) dry shipper for in-hospital transport with the use of a cryoguard. It is considered shipping if the product leaves control of trained personnel at the facility. So, if the facility is maintaining control of the products in the LN2 dry shippers while at the facility, then continuous monitoring is not required, which must be detailed in the written procedure. The facility would, however, need to show that its personnel have the documented competency to transport cell therapy products in the dry shipper within the facility and that the transport container has been validated to demonstrate it can maintain acceptable temperatures for the duration of transport. If the facility is transporting products in the dry shippers within the facility using a courier who is not an employee of the facility, then the facility would not be in compliance unless the dry shipper is continuously monitored. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for the continuous temperature monitoring of shipping containers for cryopreserved products.
  • Include criteria for defining “shipping” and scenarios requiring continuous monitoring.
• Validate all shipping containers to ensure they maintain acceptable temperatures for the duration of transport.
  • Document validation results and maintain records in the Validation Master Plan (VMP).
• Train all personnel involved in the transport of cryopreserved products on the SOP and document competency evaluations.
  • Maintain training records and ensure they are up-to-date.
• Use a log or electronic system to record and review temperature data from shipping containers.
  • Implement a process for reviewing and responding to temperature excursions.
• Conduct regular internal audits to ensure compliance with the SOP and continuous monitoring requirements.
• Document any deviations from the SOP, including CAPAs, and review them during management reviews.

5.7.4

The facility shall label shipping containers and cellular therapy products in a manner designed to allow positive identification and to inform the carrier of the appropriate handling. Reference Standards 5.6.2A, Requirements for Labeling of Cellular Therapy Products, and 5.6.2B, Requirements for Labeling Shipping Containers, apply.

☑ Actionable Checklist

• Develop and implement an SOP for labeling shipping containers and cellular therapy products.
  • Include procedures for ensuring positive identification on all labels.
  • Specify labeling requirements to inform carriers of appropriate handling.
• Create a checklist for verifying compliance with labeling requirements before shipment.
• Train staff on the SOP for labeling and handling of shipping containers and products.
  • Document all training sessions and retain records.
• Conduct regular audits of labeled products and shipping containers to ensure compliance.
• Maintain a log of all shipments, including label verification and carrier instructions.
• Review and update the labeling SOP annually or as needed based on audit findings or regulatory updates.

5.7.5

Product or package inserts and records shall accompany products being shipped or transported between facilities. When the product is transported within a facility, product or package inserts and records shall be readily available. Standard 4.3.5 and Reference Standard 5.7.5A, Labeling and Packaging Requirements upon Shipping of Cellular Therapy Products, apply.

☑ Actionable Checklist

• Develop and maintain SOPs for including product or package inserts with all shipments.
  • Ensure SOPs reference Standard 4.3.5 and Reference Standard 5.7.5A.
• Create a checklist for verifying inclusion of inserts and records before shipping.
• Implement a log for tracking shipments and verifying accompanying documentation.
• Train staff on procedures for handling and verifying inserts and records during transport.
  • Document training sessions and maintain records in personnel files.
• Conduct regular audits to ensure compliance with documentation requirements during transport.
• Review and update SOPs and training materials annually or as regulations change.

5.7.6

[Cord blood applicable]

Facilities shall maintain records of product origin, custody, transfer, identity, integrity, and acceptability.

☑ Actionable Checklist

• Develop and maintain SOPs for documenting product origin, custody, transfer, identity, integrity, and acceptability.
  • Include procedures for chain of custody documentation.
  • Specify requirements for product labeling and identification.
• Implement a tracking system for monitoring product custody and transfer.
  • Ensure system captures all necessary data points for traceability.
• Conduct regular audits of records to ensure compliance with documentation requirements.
• Train staff on procedures for maintaining product records and tracking.
  • Document all training sessions and maintain records.
• Review and update SOPs and tracking systems annually or as needed.
• Document all deviations and corrective actions related to product record maintenance.

5.8 Inspection and Testing of Products

[Cord blood applicable]

The facility shall establish and maintain policies, processes, and procedures for inspection and testing activities to verify that the specified requirements for products are met.

☑ Actionable Checklist

• Develop and maintain an SOP for the inspection and testing of cellular therapy products.
  • Include criteria for acceptance and rejection in the SOP.
• Implement a log for recording inspection and testing results.
• Train staff on inspection and testing procedures, documenting training records.
• Conduct regular audits to ensure compliance with inspection and testing SOPs.
• Review and update inspection and testing procedures annually or as needed.
• Document any deviations from inspection and testing procedures and initiate CAPAs.

5.8.1 Receipt of Incoming Cells, Tissues, and Organs

[Cord blood applicable]

At the time of receipt, incoming cells, tissues, and organs shall be inspected, sampled, and/or tested, as appropriate, to determine their acceptability. Standards 5.6.1, 5.6.3, and 5.7.6 apply. Records of the following shall be maintained:

1. Name of the supplier(s)/procurement facility.
2. Donation identification number.
3. Product description code, type of collection, and division code.
4. Product name and attributes.
5. Unique donor identifier, if applicable.
6. Unique, traceable, chain-of-identity identifier, if applicable.
7. Date and time of receipt.
8. Date and time of procurement and/or manufacture.
9. Date of expiration, if applicable.
10. Results of inspection upon receipt, if applicable, including:
    a) Product appearance.
    b) Appropriate labeling.
    c) Integrity of the container(s).
    d) Presence or absence of visible evidence of contamination and tampering.
    e) Acceptable temperature range.
11. Identity of the person receiving and/or inspecting the product.
12. Indication of acceptance, quarantine, or rejection.
13. Disposition.
14. Certificate of analysis or manufacturer’s insert or equivalent, if applicable.
15. Identification of the intended recipient, if applicable.

Guidance

Facilities that collect cellular therapy products by apheresis that are for further manufacturing by a clinical trial sponsor or manufacturer should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product.

The chain-of-identity identifier is used to communicate across the supply chain and support the maintenance of the chain of custody as medical products of human origin (MPHO) collected for cellular therapy manufacturing move through the ecosystem. The chain-of-identity identifier should be available at all steps in the process.

For further information, refer to the guidance associated with Standards 5.1.2 and 6.2.3. (SS)

#6 - The committee added subnumber 6 to this edition for completeness, ensuring that the chain of identity identifier was a part of the receipt process. This concept is new to the edition and expands on “chain of identity”, which was introduced in the previous edition. (SC)

# 10 - The committee edited subnumber 10 for language and grammar purposes, the intent of the requirement has not changed. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for the receipt and inspection of incoming cells, tissues, and organs.
  • Include procedures for inspecting product appearance, labeling, container integrity, and signs of contamination or tampering.
• Maintain a log or database to record the following details for each received product:
  • Name of the supplier/procurement facility.
  • Donation identification number and unique donor identifier, if applicable.
  • Product description code, type of collection, division code, and product attributes.
  • Date and time of receipt, procurement, and/or manufacture.
  • Date of expiration, if applicable.
  • Results of inspection upon receipt, including temperature range.
  • Identity of the person receiving and/or inspecting the product.
  • Indication of acceptance, quarantine, or rejection, and disposition.
  • Certificate of analysis or equivalent, if applicable.
  • Identification of the intended recipient, if applicable.
• Train staff on the SOP for receipt and inspection, ensuring competency evaluations are documented.
• Conduct regular audits to verify compliance with receipt and inspection procedures.
• Implement a system to ensure the chain-of-identity identifier is available and documented at all steps in the process.
• Review and update the SOP and associated logs annually or as needed to incorporate any changes in standards or practices.

5.8.1.1 Identification of Cells, Tissues, and Organs upon Receipt

The facility shall require verification of the chain of identity of cells, tissues, and organs.

☑ Actionable Checklist

• Verify receipt documentation matches the shipping manifest for all incoming cells, tissues, and organs.
  • Use SOP CT-REC-001 to guide the verification process.
• Ensure that all received materials are labeled with unique identifiers as per SOP CT-LBL-002.
• Record the condition and integrity of packaging upon receipt in the Receipt Log CT-LOG-003.
• Cross-check identifiers against the facility’s database to confirm chain of identity.
• Document any discrepancies or deviations and initiate a CAPA using Form CT-CAPA-004.
• Conduct periodic audits of receipt processes to ensure compliance with SOP CT-AUD-005.

5.8.1.2

Cells, tissues, and organs shall be quarantined upon receipt and their disposition determined by a qualified individual when any of the following occur:

1. There is a delay in inspection, labeling, sampling, or testing procedures for determination of acceptability.
2. The cells, tissues, or organs are judged as not meeting acceptance criteria.
3. The cells, tissues, or organs require further sampling, labeling, processing, or testing before disposition.
4. The cells, tissues, or organs are determined to be nonconforming, or donor eligibility has not been determined, or the donor is ineligible.

Guidance

Quarantined products need to be separated from nonquarantined products when product processing has not been completed, when the product requires further testing or labeling, or when the product does not meet acceptance criteria. Documentation that a product is in quarantine status should be easily recognizable.

Methods of quarantine may include:

• Physical quarantine of the product to make it easily distinguishable from others with quarantine labeling as required and placement in a designated area.
• Documented quarantine, in which the product is placed into quarantine through documentation electronically and/or in hard copy. (SS)

​#4 - The committee added new subnumber 4 to the edition which reads, “The cells, tissues, or organs are determined to be nonconforming, or donor eligibility has not been determined, or the donor is ineligible” recognizing that a donor with an incomplete eligibility or an ineligible donor’s cells should be quarantined and segregated appropriately. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for the quarantine of cells, tissues, and organs upon receipt.
  • Include criteria for quarantine based on delays in inspection, labeling, sampling, or testing.
  • Define procedures for handling nonconforming products or those with undetermined donor eligibility.
• Designate a physical area for quarantined products, ensuring clear separation from non-quarantined products.
  • Use distinct labeling to identify quarantined products.
• Implement an electronic and/or hard copy documentation system to record quarantine status.
  • Ensure quarantine status is easily recognizable in the documentation system.
• Train all relevant personnel on the quarantine SOP and documentation procedures.
  • Maintain training records and competency evaluations.
• Conduct regular internal audits to verify compliance with quarantine procedures and documentation accuracy.
• Document all deviations from quarantine procedures and implement CAPAs as necessary.

5.8.2 In-Process and Final Product Inspection and Testing

[Cord blood applicable]

In-process testing and monitoring shall be defined.
The facility shall:

1. Inspect and test the cellular therapy product during processing as defined by policies, processes, and procedures.
2. Quarantine the product until any required inspection, tests, processing, and eligibility determination have been completed or necessary reports received and verified, except when the product is released pursuant to Standard 5.20.3.
3. Report to the customer(s) identified in the disposition agreement any patient-specific cellular therapy products that are lost, damaged, or otherwise unsuitable for use. Standard 7.0 applies.

Guidance

The standard about agreements (#3) requires that disposition, including reasons for discard, be included in agreements. Reporting to customers about any lost, damaged, or nonconforming product should be defined in the agreement. The guidance to standards in Chapter 7, Deviations, Nonconformances, and Adverse Events, applies. (SS)

☑ Actionable Checklist

• Define and document in-process testing and monitoring procedures in SOPs.
  • Include specific tests and inspection criteria for each product type.
  • Reference SOP numbers and titles in the process documentation.
• Implement a quarantine process for products pending inspection, testing, and eligibility determination.
  • Maintain a quarantine log to track product status and release.
  • Ensure SOPs specify conditions for quarantine and release exceptions per Standard 5.20.3.
• Develop a reporting procedure for lost, damaged, or unsuitable products.
  • Include notification timelines and responsible personnel in SOPs.
  • Ensure agreements with customers include disposition and reporting requirements.
• Conduct regular training sessions on inspection, testing, and quarantine procedures.
  • Document training attendance and competency evaluations.
• Perform internal audits to verify compliance with inspection, testing, and quarantine procedures.
  • Use audit findings to update SOPs and improve processes as needed.

5.9 Storage and Preservation

The facility shall establish and maintain policies, processes, and procedures for storage of materials and cellular therapy products in order to prevent mix-ups and limit deterioration, contamination, and improper distribution of cellular therapy products. This shall include the use of designated, secure storage areas with controlled access. Chapter 7, Deviations, Nonconformances, and Adverse Events, applies.

☑ Actionable Checklist

• Develop and implement SOPs for storage of cellular therapy products to prevent mix-ups and deterioration.
  • Include procedures for labeling and segregation of products.
• Establish designated, secure storage areas with controlled access.
  • Maintain an access log for all personnel entering storage areas.
• Implement environmental monitoring of storage areas to ensure appropriate conditions.
  • Record temperature and humidity levels regularly.
• Conduct regular audits of storage practices to ensure compliance with SOPs.
• Train staff on storage procedures and document all training sessions.
• Review and update storage policies and procedures annually or as needed.

5.9.1

[Cord blood applicable]

Storage areas shall have the capacity and design to ensure that proper temperature and humidity are maintained.

Guidance

There are many types of storage areas. Storage areas may be in an open room, a designated container, or inside a temperature-controlled device such as a platelet incubator. This standard refers to storage areas in which ensuring the proper humidity and temperature are important. The intent of this standard is to ensure the storage area will not add to the potential for risk of contamination, and the integrity of supplies or reagents are not compromised due to unacceptable temperatures and humidity.

Also, the other intent of this standard is to ensure the capacity and design have been considered. The temperature and humidity measured by a sensor in one room of a large facility would not necessarily be representative of the temperature and humidity in an area farthest away from the sensors. (SS)

☑ Actionable Checklist

• Ensure storage areas have adequate capacity for all materials without overcrowding.
  • Regularly assess storage area capacity and adjust inventory levels as needed.
• Implement a system for continuous monitoring of temperature and humidity in storage areas.
  • Install calibrated sensors in multiple locations within the storage area.
  • Validate sensor placement to ensure accurate representation of conditions throughout the area.
• Develop and maintain SOPs for responding to temperature and humidity excursions.
  • Include procedures for immediate corrective actions and documentation.
• Conduct regular maintenance and calibration of temperature and humidity monitoring equipment.
  • Keep records of maintenance and calibration activities.
• Perform periodic audits of storage conditions to ensure compliance with temperature and humidity requirements.
  • Document findings and implement corrective actions as necessary.
• Train staff on the importance of maintaining proper storage conditions and the procedures for monitoring and responding to deviations.

5.9.1.1

[Cord blood applicable]

If cellular therapy products are stored in an open storage area, the ambient temperature and humidity shall be recorded at a minimum of every 4 hours.

Guidance

A product kept in open storage is also at potential risk from temperature fluctuations. Although continuous monitoring is not required, the temperature must be recorded every 4 hours. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for recording ambient temperature and humidity in open storage areas every 4 hours.
  • Include procedures for using calibrated thermometers and hygrometers.
• Train staff on the SOP for monitoring and recording ambient conditions.
  • Document training completion and maintain records.
• Maintain a log or electronic system to record temperature and humidity readings every 4 hours.
  • Ensure logs are reviewed weekly for compliance.
• Conduct regular internal audits to verify adherence to the 4-hour recording requirement.
• Implement a CAPA process for any deviations from the 4-hour recording schedule.
• Review and update the SOP and training materials annually or as needed.

5.9.2

Storage devices shall have the capacity and design to ensure that the proper temperature and/or liquid nitrogen level is maintained.

☑ Actionable Checklist

• Verify that all storage devices are capable of maintaining required temperature or liquid nitrogen levels.
  • Review and document specifications of storage devices in use.
• Implement and maintain SOPs for monitoring and recording storage conditions.
  • Ensure SOPs include procedures for regular temperature and liquid nitrogen level checks.
• Conduct and document regular calibration of temperature monitoring equipment.
  • Maintain calibration logs and certificates.
• Perform and document routine maintenance of storage devices.
  • Keep maintenance records up-to-date and accessible.
• Establish and document a contingency plan for storage device failure.
  • Train staff on the contingency plan and document training records.

5.9.3

[Cord blood applicable]

Storage devices containing cellular therapy products and critical materials shall have a system to
continuously monitor, and also record at defined intervals, the temperature and/or liquid nitrogen levels. Standard 5.7 applies.

Guidance

Storage devices containing cell therapy products or critical materials should have systems to continuously monitor temperature and/or liquid nitrogen (LN2) levels. “Continuous monitoring” generally refers to an automated system that tracks given parameters within defined set points and is able to detect any deviations outside of the acceptance limits. Automated data monitoring provides advantages of reliability compared to manual measurements, which rely on human intervention.

In addition to continuous monitoring, the facility should also record the temperature and/or LN2 levels of storage devices at defined intervals. This recording is to ensure traceability of the product or critical material to its storage condition history and may be achieved by automated or manual methods. Standards 5.9.3.1 and 5.9.3.2 further define the type of monitoring required (temperature and/or LN2 levels) based on whether products are immersed in LN2.

A product kept in open storage is also at potential risk from temperature fluctuations. Although continuous monitoring is not required, the temperature must be recorded every 4 hours. (SS)

☑ Actionable Checklist

• Implement an automated system for continuous monitoring of temperature and/or LN2 levels in storage devices.
  • Ensure the system is capable of detecting deviations outside of defined set points.
• Record temperature and/or LN2 levels at defined intervals using automated or manual methods.
  • Define and document the intervals for recording in the relevant SOP.
• Establish and maintain SOPs for monitoring and recording storage conditions, referencing SOP-5.9.3.
• Conduct regular calibration and maintenance of monitoring equipment as per the manufacturer’s recommendations.
  • Document calibration and maintenance activities in equipment logs.
• Train staff on the use of monitoring systems and the importance of maintaining storage conditions.
  • Keep training records and competency evaluations up to date.
• Review and document any deviations from defined storage conditions, implementing CAPAs as necessary.

5.9.3.1

The temperature and/or liquid nitrogen levels of freezers where cellular therapy products are immersed in liquid nitrogen shall be recorded every 24 hours, at a minimum.

☑ Actionable Checklist

• Establish and implement an SOP for daily temperature and liquid nitrogen level monitoring of freezers.
  • Include procedures for recording measurements every 24 hours.
• Train staff on the SOP and document training records.
• Use a validated log or electronic system to record daily temperature and liquid nitrogen levels.
• Conduct regular internal audits to ensure compliance with monitoring and recording procedures.
• Implement a CAPA process for any deviations in temperature or liquid nitrogen levels.
• Review and update the monitoring SOP annually or as needed based on audit findings.

5.9.3.2

The temperature of refrigerators and freezers where cellular therapy products are not immersed in liquid nitrogen shall be recorded every 4 hours, at a minimum.

☑ Actionable Checklist

• Implement a temperature monitoring system for refrigerators and freezers.
  • Ensure the system records temperature every 4 hours.
  • Integrate alerts for temperature excursions.
• Develop and maintain an SOP for temperature monitoring and recording.
• Train staff on the SOP and document training records.
• Conduct regular audits to verify compliance with temperature recording.
• Maintain a log of temperature records and review weekly.
• Document and investigate any temperature deviations and implement CAPAs.

5.9.4

[Cord blood applicable]

Storage devices containing cellular therapy products and/or critical materials shall have an alarm system that is set to activate under conditions that will allow proper action to be taken before products or reagents reach unacceptable conditions. Alarm activation shall require personnel to investigate and document the condition activating the alarm and to take immediate corrective action as necessary.

Procurement Activities

☑ Actionable Checklist

• Ensure all storage devices for cellular therapy products have functional alarm systems.
  • Test alarm systems monthly and document results in the Alarm Test Log.
• Set alarm thresholds to activate before products reach unacceptable conditions.
  • Review and update alarm threshold settings quarterly.
• Train personnel on alarm response procedures and document training in the Training Records.
• Investigate and document all alarm activations in the Alarm Incident Log.
  • Include details of the condition, corrective actions taken, and resolution.
• Review alarm incident logs during monthly management reviews to identify trends and areas for improvement.

5.10 Donor Evaluation

[F]

Donor evaluation shall be performed and informed consent obtained, in accordance with Reference Standards 4.5A, Donor Informed Consent or Authorization; Reference Standard 5.10A, General Requirements for Cellular Therapy Product Donors; Reference Standard 5.10B, Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors; Reference Standard 5.10C, Clinical Evaluation and Laboratory Testing of Autologous Donors; Reference Standard 5.10D, Clinical Evaluation and Laboratory Testing of Mothers of Cord Blood or Gestational Material Donors; and Reference Standard 5.10E, Clinical Evaluation and Laboratory Testing of Cadaveric Donors.

Guidance

The US FDA lists those diseases considered to be “relevant” per 21 CFR 1271.3(r). (SS)

☑ Actionable Checklist

• Develop and implement SOPs for donor evaluation, referencing Standards 4.5A, 5.10A-E.
  • Include procedures for obtaining informed consent per Standard 4.5A.
  • Outline clinical evaluation and laboratory testing requirements for all donor types.
• Maintain a checklist for clinical evaluation and laboratory testing of donors, ensuring compliance with Standards 5.10A-E.
• Train staff on donor evaluation SOPs and informed consent procedures, documenting training records.
• Conduct regular audits of donor evaluation processes to ensure adherence to SOPs and regulatory standards.
• Document and review any deviations or CAPAs related to donor evaluation processes in the quality management system.
• Update crosswalk documents to map donor evaluation SOPs to AABB and FACT-JACIE standards.

5.10.1 Medical Suitability

The facility shall define medical suitability criteria to protect the safety of the donor and the intended recipient. Medical suitability shall be determined before the initiation of any intervention that could potentially affect the health of a donor or recipient. The facility shall identify donor medical conditions that may adversely affect the potential therapeutic value of the cellular therapy product. This evaluation shall be conducted by a health-care professional
and shall include, based on examination, clinical history, and relevant medical record(s):

☑ Actionable Checklist

• Develop and maintain an SOP for determining medical suitability criteria for donors and recipients.
  • Include criteria for identifying donor medical conditions that may affect product therapeutic value.
  • Detail the process for conducting evaluations by healthcare professionals.
• Create a checklist or form for documenting medical suitability evaluations.
  • Ensure it includes sections for examination findings, clinical history, and relevant medical records.
• Train healthcare professionals on the SOP for medical suitability evaluations.
  • Maintain training records and competency evaluations for all involved staff.
• Conduct regular audits to ensure compliance with the medical suitability SOP.
  • Document findings and implement corrective actions as needed.
• Review and update the medical suitability criteria annually or as needed based on new evidence or regulatory changes.
  • Document the review process and any changes made.

5.10.1.1

The ability to tolerate the collection procedure.

☑ Actionable Checklist

• Develop and implement an SOP for assessing patient tolerance to the collection procedure.
  • Include criteria for assessing patient eligibility and tolerance.
  • Outline steps for monitoring patient during the procedure.
• Train staff on the SOP for assessing and monitoring patient tolerance.
  • Document all training sessions and maintain training records.
• Conduct competency evaluations for staff on patient assessment and monitoring.
  • Keep records of all competency evaluations.
• Maintain a log of all collection procedures, noting any tolerance issues.
• Review and analyze tolerance data regularly to identify trends or areas for improvement.
• Implement CAPAs for any identified issues with patient tolerance during collection.

5.10.1.2

Risk of any acquired condition, such as malignancy, or any inherited condition that could be transferred to the recipient by the transplant.

Guidance

Standard 5.10.1 refers to the evaluation of cellular therapy donors for risks related to the donation process and potential noninfectious risks to the recipient. These criteria are derived from the donor physical exam and health history. Standard 5.10.1.2 would typically apply only to allogeneic donors and would be irrelevant for autologous donors. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for evaluating donor health history and physical exam results for risks of acquired or inherited conditions.
  • Include criteria for identifying conditions that may pose a risk to recipients.
  • Reference relevant medical guidelines and risk assessment tools.
• Train staff on the SOP for donor evaluation and risk assessment.
  • Maintain training records and competency evaluations.
• Document all donor evaluations, including identified risks and decision-making rationale.
  • Use standardized forms or electronic health records.
• Conduct regular audits of donor evaluation processes to ensure compliance with SOPs.
  • Review a sample of donor records for adherence to risk assessment criteria.
• Implement a process for reviewing and updating the donor evaluation SOP based on new medical evidence or regulatory changes.
  • Schedule annual reviews and document any revisions.

5.10.1.3

If applicable, risk for hemoglobinopathy.

Guidance

The administration of mobilizing agents such as granulocyte colony-stimulating factor (G-CSF) may pose a risk to the donor, as it has been associated with morbidity and mortality in donors with sickle cell disease and with compound hemoglobinopathies such as sickle-beta-thalassemia. There should be a process for, or documentation of, the risk evaluation for hemoglobinopathy, such as asking a relevant question in the donor history questionnaire or testing for the presence of hemoglobin S. (SS)

5.10.1.3.1

For HPC, Apheresis and HPC, Marrow, the donor evaluation criteria shall include risk for hemoglobinopathy.

☑ Actionable Checklist

• Develop and implement an SOP for evaluating donor risk for hemoglobinopathy.
  • Include specific criteria for identifying donors at risk.
  • Outline procedures for donor history questionnaire administration.
• Incorporate a question regarding hemoglobinopathy risk in the donor history questionnaire.
• Establish a testing protocol for hemoglobin S for donors with potential risk factors.
• Train staff on identifying and managing donors with hemoglobinopathy risk.
  • Document training sessions and maintain records.
• Perform regular audits of donor evaluations to ensure compliance with hemoglobinopathy risk assessment.
• Review and update the SOP annually or as needed based on audit findings and regulatory updates.

5.10.1.4

If applicable, pregnancy evaluation.

☑ Actionable Checklist

• Develop and implement an SOP for pregnancy evaluation in applicable cases.
  • Include criteria for when pregnancy evaluation is required.
  • Specify methods for conducting pregnancy evaluations.
• Train relevant staff on the pregnancy evaluation SOP and document training records.
• Maintain a log of all pregnancy evaluations conducted, including results and any follow-up actions.
• Perform regular audits to ensure compliance with the pregnancy evaluation SOP.
• Review and update the pregnancy evaluation SOP annually or as needed based on regulatory changes.

5.10.1.5

If applicable, the administering facility shall ensure that HLA typing is performed on the donor and verify that the HLA type meets specified HLA requirements. Reference Standard 5.10B, Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors; Reference Standard 5.15B, Processing Tests for HPC, Cord Blood Products or Gestational Materials; Reference Standard 5.15C, Processing Tests for Cellular Therapy Products Other than HPC, Apheresis; HPC, Marrow; and HPC, Cord Blood or Gestational Materials, apply.

Guidance

The standards stipulate what information the clinical program should include in policies, processes, and procedures regarding administration. This section includes criteria for selecting donors before the initiation of preadministration interventions. HLA typing of the donor is one of these required criteria. However, not all products trigger the need to perform HLA typing, such as those from autologous donors. (SS)

5.10.1.5.1

HLA typing shall be performed by a facility accredited by the American Society for Histocompatibility and Immunogenetics (ASHI), College of American Pathologists
(CAP), European Federation for Immunogenetics (EFI), or other equivalent accrediting body.

5.10.1.5.2

For HPC, Apheresis and HPC, Marrow intended for allogeneic transplantation, the donor evaluation criteria shall include HLA matching.

☑ Actionable Checklist

• Verify that HLA typing is performed on all applicable donors.
  • Ensure that HLA typing meets specified HLA requirements as per SOP CT-5.10.1.5.
• Confirm that HLA typing is conducted by an accredited facility (ASHI, CAP, EFI, or equivalent).
  • Maintain a list of accredited facilities and their current accreditation status.
• Include HLA matching in donor evaluation criteria for HPC, Apheresis, and HPC, Marrow intended for allogeneic transplantation.
  • Reference SOP CT-5.10.1.5.2 for detailed donor evaluation criteria.
• Document all HLA typing results and verification processes in the donor’s medical record.
• Conduct regular audits to ensure compliance with HLA typing and matching requirements.
• Review and update SOPs related to HLA typing and donor evaluation annually or as needed.

5.10.1.6

The facility shall have a policy that addresses the privacy and confidentiality of the medical suitability determination process.

Guidance

Facilities should provide a private area to conduct the donor consent and donor suitability process. Facilities should consider a separate interview room, ensuring that donors can speak openly and freely concerning their history. (SS)

☑ Actionable Checklist

• Develop and implement a policy addressing privacy and confidentiality during the medical suitability determination process.
  • Reference SOP for conducting donor interviews in private settings.
  • Include procedures for maintaining confidentiality of donor information.
• Designate a private area or separate interview room for donor consent and suitability assessments.
  • Ensure the room is equipped to maintain privacy and confidentiality.
• Train staff on the importance of privacy and confidentiality in the donor suitability process.
  • Document training sessions and maintain records in the training log.
• Conduct regular audits to ensure compliance with privacy and confidentiality policies.
  • Use an audit checklist to verify adherence to the policy and SOPs.
• Review and update the policy and SOPs annually or as needed based on audit findings or regulatory changes.
  • Document all reviews and updates in the management review log.

5.10.1.7

The facility shall define criteria for evaluating pediatric donors.

Guidance

A pediatric donor is a young person or teenager (usually under the age of 18 in the United States) who is not of legal age to consent to a medical procedure or provide informed consent for donation of cellular therapy products. A pediatric donor may also be called an adolescent, minor, or juvenile. Persons of this age may not understand the importance of full disclosure on the donor history questionnaire regarding risks of sexually transmitted and communicable diseases. (SS)

☑ Actionable Checklist

• Develop and document SOPs for evaluating pediatric donors, including specific criteria.
  • Include age-specific consent and assent processes in SOPs.
  • Define medical and psychological assessment criteria for pediatric donors.
• Create a pediatric donor evaluation form to capture all necessary information.
• Train staff on the unique aspects of pediatric donor evaluation and consent.
  • Maintain training records and competency evaluations for staff involved in pediatric donor assessments.
• Conduct regular audits of pediatric donor evaluations to ensure compliance with defined criteria.
• Review and update the pediatric donor evaluation criteria annually or as needed based on new guidelines or regulations.

5.10.2 Donor Eligibility

Donor eligibility, when required, shall be determined before the initiation of any intervention that
could potentially affect the health of a recipient.

☑ Actionable Checklist

• Develop and implement an SOP for donor eligibility determination prior to interventions.
  • Include criteria for medical history, risk factors, and laboratory testing.
• Train staff on donor eligibility SOP and document completion in training records.
• Maintain a log of donor eligibility assessments, including dates and outcomes.
• Conduct regular audits of donor eligibility determinations to ensure compliance.
• Implement a CAPA process for any deviations identified in donor eligibility assessments.
• Review and update the donor eligibility SOP annually or as regulations change.

5.10.2.1

The facility shall define donor eligibility criteria to protect the safety of the intended recipient.

Guidance

Donors should be evaluated for risk factors and clinical evidence of relevant communicable disease
agents and diseases for the purpose of preventing the transmission of infectious diseases that could
harm the intended recipient. (SS)

5.10.2.1.1

Donor eligibility criteria shall include:

1. Donor screening including a physical exam, review of relevant medical records, and a current medical history interview to identify risk for relevant communicable disease.
2. Testing.

Guidance

The facility that determines the donor eligibility status should review these items. Donor health history is derived from the donor history questionnaire. Relevant medical records can include laboratory test results, medical records, coroner and autopsy reports, records, or other information received from any source pertaining to a history of risk factors for relevant communicable disease agents and diseases.

For products collected for autologous use, the donor is the same individual as the patient. Based on the clinical situation, the donor history questionnaire may be different for autologous vs allogeneic donors. Donors should be screened using Competent-Authority-approved tests or kits and according to the manufacturer’s instructions. (SS)

5.10.2.1.2

The facility shall have a policy that addresses and ensures the privacy and confidentiality of the donor eligibility determination process.

Guidance

Facilities should provide a private area to conduct the donor eligibility process. Facilities should consider a separate interview room, ensuring that donors can speak openly and freely concerning their history. (SS)

☑ Actionable Checklist

• Develop and document SOPs for donor eligibility criteria, including risk assessment for communicable diseases.
  • Include procedures for conducting physical exams and reviewing medical records.
  • Outline the process for medical history interviews using a donor history questionnaire.
• Implement testing protocols using Competent-Authority-approved tests or kits.
  • Ensure adherence to manufacturer’s instructions for all testing procedures.
• Maintain a log of all donor screenings, including results from physical exams, medical history interviews, and testing.
• Establish a policy ensuring privacy and confidentiality during the donor eligibility determination process.
  • Designate a private area or room for conducting donor interviews.
• Conduct regular training for staff on donor eligibility criteria and privacy policies.
  • Keep records of training sessions and competency evaluations.
• Perform internal audits to ensure compliance with donor eligibility SOPs and privacy policies.
  • Document findings and implement corrective actions as needed.

5.10.2.2 Collection of Samples for Infectious Disease Testing

[F]

Samples associated with the products listed below shall be collected within the following time frames, unless FDA or relevant Competent Authority regulations are more stringent:

1. HPC, Cord Blood: Obtain maternal sample within 7 days before or after collection.
2. HPC, Marrow and HPC, Apheresis: Collect from the donor within 30 days before procurement.
3. All other cellular therapy products: Collect from the donor within 7 days before or after procurement.

Guidance

Standard 5.10.2.2 is a commonly cited standard for nonconformances. For example, nonconformances have been given because the collection date of the maternal sample associated with HPC, Cord Blood products is not documented, so it is not possible to determine if the sample was collected within 7 days before or after delivery. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for the collection of samples for infectious disease testing, specifying time frames for each product type.
  • Include procedures for documenting collection dates to ensure compliance with time frames.
• Create a log or form to record the collection date of maternal samples for HPC, Cord Blood, ensuring it is within 7 days before or after collection.
• Establish a tracking system to monitor the collection dates for HPC, Marrow, and HPC, Apheresis samples, ensuring they are collected within 30 days before procurement.
• Implement a review process to verify that all other cellular therapy product samples are collected within 7 days before or after procurement.
• Conduct regular audits to ensure compliance with sample collection time frames and document findings.
• Train staff on the importance of adhering to sample collection time frames and maintaining accurate documentation.

5.10.2.3 Cadaveric Donor Eligibility

[F]

The evaluation of the donor’s eligibility required by Reference Standard 5.10A, General Requirements for Cellular Therapy Product Donors, shall be performed by interviewing a family member or other knowledgeable person.

Guidance

Cadaveric pancreases are almost exclusively the tissue source for allogeneic pancreatic islet products, and, unless a center demonstrates that it uses living donor pancreases as a tissue source, Standard 5.10.2.3 for cadaveric donors applies to facilities working with islets. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for conducting interviews with family members or knowledgeable persons regarding cadaveric donor eligibility.
  • Include a checklist of required information to be gathered during the interview.
  • Define roles and responsibilities for personnel conducting the interviews.
• Train staff involved in donor eligibility interviews on the SOP and document training completion.
• Maintain a log of all interviews conducted, including date, interviewer, and interviewee details.
• Regularly review and update the SOP based on feedback from interviews and changes in regulations.
• Conduct internal audits to ensure compliance with the SOP and document findings.
• Implement a CAPA process for addressing any deviations identified during audits or interviews.

5.10.2.4

[F]

Donor testing shall be performed in conformance with Reference Standard 5.10B, Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors; Reference Standard 5.10C, Clinical Evaluation and Laboratory Testing of Autologous Donors; Reference Standard 5.10D, Clinical Evaluation and Laboratory Testing of Mothers of Cord Blood or Gestational Material Donors; and Referene Standard 5.10E, Clinical Evaluation and Laboratory Testing of Cadaveric Donors.

☑ Actionable Checklist

• Ensure SOPs for donor testing align with Reference Standards 5.10B, 5.10C, 5.10D, and 5.10E.
  • Review and update SOPs annually or as standards change.
• Maintain a log of all donor tests performed, including dates and results.
• Verify that all donor testing personnel are trained and competency assessed on relevant SOPs.
• Conduct regular audits to ensure compliance with donor testing procedures.
• Document and review any deviations from donor testing protocols, implementing CAPAs as necessary.
• Include donor testing procedures in the Validation Master Plan (VMP) for process control.

5.10.2.5

There shall be a process to evaluate samples when the level of plasma dilution may affect test results.*

*FDA Guidance: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (August 8, 2007).
21 CFR 1271.80.

5.10.2.5.1

If plasma dilution is potentially sufficient to affect infectious disease testing results, the donor shall be considered ineligible unless one of the following conditions is met:

1. A suitable new sample is collected and used for testing.
2. A suitable sample before transfusion and/or infusion is used for testing.
3. An appropriate algorithm is applied to determine that plasma dilution has not affected the acceptability of the blood sample.

5.10.2.5

Source data lists 5.10.2.5 more than once. This second copy is preserved for completeness; cross-references resolve to the first.

There shall be a process to evaluate samples when the level of plasma dilution may affect test results.*

*FDA Guidance: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (August 8, 2007).
21 CFR 1271.80.

5.10.2.5.1

Source data lists 5.10.2.5.1 more than once. This second copy is preserved for completeness; cross-references resolve to the first.

If plasma dilution is potentially sufficient to affect infectious disease testing results, the donor shall be considered ineligible unless one of the following conditions is met:

1. A suitable new sample is collected and used for testing.
2. A suitable sample before transfusion and/or infusion is used for testing.
3. An appropriate algorithm is applied to determine that plasma dilution has not affected the acceptability of the blood sample.

☑ Actionable Checklist

• Develop and implement an SOP for evaluating plasma dilution in donor samples.
  • Include criteria for determining when plasma dilution may affect test results.
  • Outline procedures for collecting new samples or using pre-transfusion samples.
  • Describe the algorithm used to assess the impact of plasma dilution.
• Train staff on the SOP for evaluating plasma dilution and document training records.
• Maintain a log of all donor samples evaluated for plasma dilution and the outcomes.
• Conduct periodic audits to ensure compliance with the SOP and document findings.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.
• Document any deviations from the SOP and implement CAPAs as necessary.

☑ Actionable Checklist

• Develop and implement an SOP for evaluating plasma dilution in donor samples.
  • Include criteria for assessing the impact of plasma dilution on test results.
• Train staff on the SOP for plasma dilution evaluation and document training records.
• Establish a log for recording instances of plasma dilution evaluation and outcomes.
• Create a process for collecting new samples when plasma dilution affects test results.
  • Ensure documentation of sample collection and testing in donor records.
• Implement an algorithm to assess the impact of plasma dilution on sample acceptability.
  • Validate the algorithm and document validation results.
• Conduct regular internal audits to ensure compliance with plasma dilution evaluation procedures.

5.10.2.6

All donor infectious disease testing shall be performed using assays in accordance with the manufacturer’s written instructions that have been approved for donor screening by the FDA or relevant Competent Authority, if such assays are available. Standard 4.3.5 applies.

☑ Actionable Checklist

• Verify that all infectious disease testing assays used are FDA-approved or approved by the relevant Competent Authority for donor screening.
  • Maintain a current list of approved assays and their manufacturer instructions.
• Ensure that all testing is performed strictly according to the manufacturer’s written instructions.
  • Review and update SOPs to align with the manufacturer’s instructions for each assay.
• Conduct regular training sessions for staff on the proper use of approved assays.
  • Document training completion and competency evaluations in personnel files.
• Perform internal audits to confirm compliance with assay use and documentation.
  • Use the AABB Assessment Tool to guide audit focus on infectious disease testing.
• Document any deviations from the manufacturer’s instructions and implement CAPAs as necessary.
  • Review and approve CAPAs in management review meetings.
• Keep records of all infectious disease testing results, including assay lot numbers and expiration dates.

5.10.2.7

Infectious disease testing shall be performed on all donors of products with the potential for allogeneic use.

☑ Actionable Checklist

• Develop and maintain an SOP for infectious disease testing of allogeneic donors.
  • Include criteria for donor eligibility and testing timelines.
• Ensure all infectious disease testing is performed using FDA-approved or cleared assays.
• Maintain a log of all donor infectious disease test results.
• Conduct regular audits to verify compliance with infectious disease testing SOP.
• Train staff on infectious disease testing procedures and document training records.
• Review and update the SOP annually or as regulations change.

5.10.2.8

The following tests shall be performed:

1. Hepatitis B virus (HBsAg; anti-HBc; HBV DNA).
2. Hepatitis C virus (anti-HCV; HCV RNA).
3. Human immunodeficiency virus (anti-HIV-1/2; HIV-1 RNA).
4. Human T-cell lymphotropic virus, type I and II (anti-HTLV-I/II), for viable leukocyte- rich products only.
5. Antibody to cytomegalovirus for viable leukocyte-rich products only.
6. A serologic test for syphilis.*
7. West Nile virus (WNV RNA).

Reference Standard 5.10B, Clinical Evaluation and Laboratory Testing of Living Allogeneic
Donors; Reference Standard 5.10C, Clinical Evaluation and Laboratory Testing of Autologous Donors; Reference Standard 5.10D, Clinical Evaluation and Laboratory
Testing of Mothers of Cord Blood or Gestational Material Donors; and Reference Standard 5.10E, Clinical Evaluation and Laboratory Testing of Cadaveric Donors, apply.

*FDA Guidance for Industry: Use of Donor Screening Tests to Test Donors of Human Cells, Tissues and Cellular and Tissue-Based Products for Infection with Treponema pallidum (Syphilis) (September 2015).

5.10.2.8.1

For facilities not subject to US laws and regulations, HBV DNA testing is acceptable in place of anti-HBc testing. Standards 1.4, 5.10.7, and Reference Standard 5.10B Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors apply.

Guidance

Facilities outside the United States considering the discontinuation of anti-HBc antibody testing should develop policies to facilitate the exportation of cellular therapy products to the United States and other clinical facilities that do require testing, for either testing before release or distribution via a declaration of urgent medical need (DUMN). (SS)

5.10.2.8.2

Facilities not subject to US laws and regulations shall conform to the following alternatives if testing of donors for West Nile virus is not required by their Competent Authority:

1. Facilities shall determine all donors to be ineligible for a minimum of 28 days if they have traveled to WNV-endemic areas as determined by the Competent Authority (eg, WHO, CDC, or ECDC surveillance maps).
2. Facilities shall determine all donors to be ineligible for a minimum of 120 days if they have tested positive for or have a history of WNV.^¶

Standards 1.4, 5.10.7, and Reference Standard 5.10B Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors, apply.

^¶FDA Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (August 2007)

5.10.2.8.3

Facilities not subject to US laws and regulations, and where testing for T. cruzi is not required by the facility’s Competent Authority, shall determine all donors to be ineligible if any of the following apply:

1. Donors have tested positive for T. cruzi.
2. Donors have a history of T. cruzi infection.
3. Donors have a health history or environmental risk factors for T. cruzi that would be identified by the donor screening process.

Standards 1.4, 5.10.7, and Reference Standard 5.10B Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors apply.

☑ Actionable Checklist

• Ensure all donor testing includes HBsAg, anti-HBc, and HBV DNA, or HBV DNA in place of anti-HBc for non-US facilities.
  • Reference SOP for Donor Testing: SOP-001.
• Verify testing for anti-HCV and HCV RNA is conducted for all donors.
  • Document results in Donor Testing Log: LOG-002.
• Confirm anti-HIV-1/2 and HIV-1 RNA tests are performed for each donor.
  • Use the HIV Testing Form: FORM-003.
• Conduct anti-HTLV-I/II and CMV antibody tests for viable leukocyte-rich products.
  • Update records in Viable Product Testing Log: LOG-004.
• Perform serologic test for syphilis on all donors.
  • Follow FDA Guidance for Syphilis Testing.
• Ensure WNV RNA testing is completed for each donor.
  • Record outcomes in WNV Testing Log: LOG-005.

5.10.2.9

Testing shall be performed by a laboratory qualified by the FDA or relevant Competent Authority (eg, CMS) and shall meet testing requirements for donors of cellular therapy products in that country.

Guidance

Products that are procured or transferred under a registry-mediated process (such as via NMDP) would meet the intent of this standard. (SS)

☑ Actionable Checklist

• Verify that the laboratory performing donor testing is qualified by the FDA or relevant Competent Authority.
  • Maintain documentation of the laboratory’s qualifications and certifications.
• Ensure that the laboratory meets all testing requirements for donors of cellular therapy products in the relevant country.
  • Review and update SOPs to reflect current testing requirements.
• Conduct a gap analysis to confirm compliance with testing standards for all donor products.
  • Document findings and implement corrective actions if necessary.
• Establish a process for regular review and verification of laboratory qualifications and testing compliance.
  • Schedule and document periodic audits of laboratory compliance.
• Maintain records of all donor testing, including laboratory reports and compliance verification.
  • Use a standardized form or log to capture and track testing information.

5.10.2.10

The facility shall ensure relevant infectious diseases and emerging infectious diseases are addressed, and action taken in regard to the donor screening and testing process.^†

^†FDA Guidance for Industry: Recommendations to Reduce the Risk of Transmission of Mycobacterium tuberculosis (Mtb) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (January 2025).

FDA Guidance for Industry: Recommendations to Reduce the Risk of Transmission of Disease Agents Associated with Sepsis by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (January 2025).

Guidance

The facility policies should define how information is obtained regarding emerging infectious disease and relevant communicable disease agents and diseases, and the process for making any needed changes that result from this information.

Regulatory agencies may determine that an emerging infectious disease can pose a risk to recipients of cellular therapy products derived from infected donors. Facilities should have policies, processes, and procedures in place to routinely check with the relevant regulatory agency for identification and guidance on appropriate interventions regarding emerging infectious diseases. For example, facilities could regularly check with the World Health Organization, the FDA in the United States, or the equivalent regulatory body if outside the United States. The facilities should have a plan to implement recommended interventions such as additional screening questions or additional testing. (SS)

The committee added references to the two new FDA guidances concerning Mycobacterium tuberculosis and Sepsis for completeness. This ensures that individuals implementing the standards are aware of the guidances. Recognizing that these guidances were reissued by the FDA for public comment, the references may be edited by the committee following the publication of the edition. (SC)

☑ Actionable Checklist

• Develop and document SOPs for obtaining information on emerging infectious diseases from regulatory agencies.
  • Include procedures for regular checks with WHO, FDA, or equivalent bodies.
• Implement a process for updating donor screening and testing protocols based on new guidance.
  • Maintain a log of updates and changes made to protocols.
• Train staff on new SOPs and updates related to infectious disease screening and testing.
  • Keep training records and competency evaluations current.
• Establish a review mechanism for assessing the impact of new infectious disease information on donor eligibility.
  • Document review outcomes and actions taken.
• Conduct regular internal audits to ensure compliance with updated screening and testing processes.
  • Use audit findings to inform continuous improvement efforts.
• Maintain a crosswalk document mapping SOPs to AABB Standard 5.10.2.10 and relevant FDA guidances.

5.10.3 Samples for Testing Donations after Brain or Cardiac Death

☑ Actionable Checklist

• Develop and implement an SOP for collecting samples from donations after brain or cardiac death.
  • Ensure the SOP includes criteria for sample collection timing and handling.
• Train staff on the SOP for sample collection from donations after brain or cardiac death.
  • Maintain training records and competency evaluations for all relevant staff.
• Establish a log for tracking samples collected from donations after brain or cardiac death.
• Perform regular audits to ensure compliance with the SOP for sample collection.
• Document any deviations from the SOP and implement CAPAs as necessary.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.10.3.1

Blood samples for testing shall be collected before the cessation of the donor’s circulation, if possible.

5.10.3.1.1

If blood is collected after cessation of circulation, infectious disease testing of samples shall be performed using assays that have been approved for donor screening by the FDA or relevant Competent Authority and specifically labeled for cadaveric specimens, when available.

☑ Actionable Checklist

• Develop and implement an SOP for collecting blood samples before cessation of donor circulation.
  • Include procedures for documenting the time of sample collection relative to cessation of circulation.
• Establish a protocol for using FDA-approved assays for infectious disease testing on post-circulation samples.
  • Ensure assays are specifically labeled for cadaveric specimens, when available.
• Maintain a log of all blood sample collections, noting the timing relative to cessation of circulation.
• Conduct regular training sessions for staff on the SOP for blood sample collection and testing requirements.
  • Keep training records and competency evaluations up to date.
• Perform regular audits to ensure compliance with SOPs and regulatory requirements for blood sample collection and testing.
• Document any deviations from the SOP and implement corrective and preventive actions (CAPAs) as necessary.

5.10.4 Evaluation of Cellular Therapy Products

[F]

Before shipment or transport of cellular therapy products, the receiving facility shall review the donor screening and infectious disease testing records for compliance with applicable local and FDA or relevant Competent Authority regulations for the receiving facility, to ensure the product meets specified requirements.

Guidance

When a product is being shipped through a registry, the registry is responsible for reviewing this information and ensuring that relevant donor screening and infectious disease testing results are communicated to the receiving facility. However, this should be specified in agreements. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for reviewing donor screening and infectious disease testing records prior to shipment.
  • Include criteria for compliance with FDA and local regulations.
  • Specify roles and responsibilities for review and approval.
• Create a checklist or form for documenting the review of donor screening and testing records.
  • Ensure the form includes fields for compliance verification and reviewer signature.
• Establish agreements with registries to clarify responsibilities for reviewing and communicating donor information.
  • Review and update agreements annually or as needed.
• Train relevant staff on the SOP and use of the checklist/form.
  • Maintain training records and conduct competency evaluations annually.
• Conduct regular internal audits to verify compliance with the SOP and documentation requirements.
  • Document findings and implement corrective actions as necessary.

5.10.5

[F]

A final determination of donor eligibility for allogeneic donors shall be made and shall include the following information:

1. A statement that the donor has been determined to be eligible or ineligible, noting the name and address of the facility that made the donor eligibility determination. Standards 5.10.1.5.1 and 5.10.8 apply.
2. A statement that the infectious disease testing was performed by a laboratory that has been certified to perform such testing on human samples under CLIA regulations or that has met equivalent requirements as determined by the CMS. For facilities located outside of the United States, the use of a laboratory authorized as a testing center by the FDA or relevant Competent Authority is permissible.
3. For a product from an ineligible donor, a statement noting the reason(s) for the determination of ineligibility.

☑ Actionable Checklist

• Develop and maintain an SOP for documenting donor eligibility determinations, including facility name and address.
  • Ensure SOP references Standards 5.10.1.5.1 and 5.10.8.
• Implement a form or electronic system to record donor eligibility status, including eligible/ineligible determination.
• Verify that infectious disease testing is conducted by a CLIA-certified laboratory or equivalent.
  • Maintain a list of approved laboratories with certification details.
• Document reasons for ineligibility for products from ineligible donors in the donor record.
• Conduct regular audits to ensure compliance with donor eligibility documentation requirements.
• Train staff on the donor eligibility determination process and documentation requirements.

5.10.6 Abnormal Results on Donor Screening and Testing

☑ Actionable Checklist

• Develop and maintain an SOP for managing abnormal donor screening and testing results.
  • Include criteria for identifying abnormal results.
  • Outline steps for notifying relevant personnel.
• Implement a log to document all abnormal results and actions taken.
• Train staff on recognizing and responding to abnormal results.
  • Conduct initial and annual competency evaluations.
• Establish a review process for abnormal results to identify trends.
  • Document findings and corrective actions in management reviews.
• Ensure all abnormal results are reviewed and signed off by a qualified medical director.
• Perform regular audits of abnormal result management to ensure compliance with SOPs.

5.10.6.1

The facility shall establish policies, processes, and procedures for notification of abnormal or reactive infectious disease test results. Standard 7.2.4 applies.

☑ Actionable Checklist

• Develop and document an SOP for notification of abnormal or reactive infectious disease test results.
  • Include a step-by-step process for identifying and documenting abnormal results.
  • Specify responsible personnel for notification and documentation.
• Create a notification log to record all instances of abnormal or reactive test results.
• Implement a training program for staff on the notification process.
  • Maintain training records and competency evaluations.
• Conduct regular audits to ensure compliance with the notification SOP.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.10.6.2

[F]

Abnormal findings on donor screening, examination, and review of relevant clinical history or testing that may affect the donor’s health shall be communicated to the donor or donor’s physician. Reference Standard 4.5A, Donor Informed Consent or Authorization, and Reference Standard 4.7A, Patient Informed Consent, apply.

5.10.6.2.1

For cord blood or gestational materials, the donor’s mother or appropriate physician shall be notified.

5.10.6.2.2

For cadaveric donors, all infectious disease test results shall be reported to the procurement facility. The procurement facility shall report positive test results to appropriate authorities as mandated by law or regulation, and test results shall be made available to the donor’s legal next
of kin when the test result(s) could affect the health of others.

☑ Actionable Checklist

• Develop and implement an SOP for communicating abnormal findings to donors or their physicians.
  • Include procedures for documenting communications in donor records.
• Ensure SOPs for cord blood or gestational materials include notification procedures for the donor’s mother or appropriate physician.
• Create a protocol for reporting infectious disease test results for cadaveric donors to the procurement facility.
  • Include steps for the procurement facility to report positive results to authorities as required by law.
• Maintain a log for tracking all communications of abnormal findings and test results.
• Train staff on the SOPs related to donor communication and reporting requirements.
  • Document training sessions and maintain records of staff competency evaluations.
• Conduct regular audits to ensure compliance with communication and reporting SOPs.

5.10.6.3

[F]

Abnormal findings on donor screening, examination, or review of relevant clinical history or testing that may affect the recipient’s health or the therapeutic value of the cellular therapy product shall be communicated to the recipient’s physician and to the recipient before distribution of the cellular therapy product for clinical use. Reference Standard 4.5A, Donor Informed Consent or Authorization, and Reference Standard 4.7A, Patient Informed Consent, apply.

☑ Actionable Checklist

• Develop an SOP for communicating abnormal donor findings to the recipient’s physician and recipient.
  • Include steps for documenting the communication process.
  • Reference SOPs for Donor Informed Consent and Patient Informed Consent.
• Train staff on the SOP for communication of abnormal findings.
  • Maintain training records and competency evaluations.
• Create a form or log to document abnormal findings and communication details.
  • Ensure the form includes date, time, and personnel involved in the communication.
• Conduct regular audits to ensure compliance with communication procedures.
  • Review logs and records during audits for completeness and accuracy.
• Implement a process for reviewing and updating the SOP and related documents annually.
  • Document any changes and ensure all staff are trained on updates.
• Establish a CAPA process for addressing any deviations in communication procedures.
  • Document all deviations and corrective actions taken.

5.10.6.4

[Cord blood applicable]

Records of donors determined ineligible after procurement of the product shall be maintained.

5.10.6.4.1

Records of cord blood or gestational material donors shall include the birth mother and, if applicable, the biologic mother.

☑ Actionable Checklist

• Maintain a log of all donors determined ineligible after procurement, including details of ineligibility.
  • Ensure the log includes identifiers for both the birth mother and the biologic mother, if applicable.
• Develop and implement an SOP for documenting donor eligibility status post-procurement.
• Regularly review and update the donor records to ensure completeness and accuracy.
• Conduct periodic audits of donor records to verify compliance with documentation requirements.
• Train staff on the procedures for maintaining and updating donor eligibility records.
• Include donor eligibility record maintenance in the internal audit schedule and document findings.

5.10.7 Products from Ineligible Donors

[F]

The biohazard label shall be attached to any allogeneic product for which there are abnormal donor screening or testing results. All allogeneic products from ineligible donors shall be provided only under urgent medical need and according to local and/or FDA or relevant Competent Authority regulations. The product shall be labeled with the phrase “WARNING: Advise patient of communicable disease risks.” Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products, applies.

Guidance

These standards require documentation of urgent medical need in order to provide allogeneic products from donors that have been deemed ineligible, regardless of whether they are being used for a first- or second-degree blood relative. The committee believes this falls under best practices and made the decision to exceed current FDA requirements, which allow this limited use in 21 CFR 1271.65(b). The committee wanted to ensure that transplant physicians and recipients were aware of any risks associated with infusion of the product, and this additional documentation should ensure that this is the case. (SS)

The committee added the phrase, “and according to local and/or FDA and relevant Competent Authority regulations” to the standard for completeness. (SC)

☑ Actionable Checklist

• Attach a biohazard label to any allogeneic product with abnormal donor screening or testing results.
  • Verify the presence of the biohazard label before product release.
• Ensure allogeneic products from ineligible donors are provided only under urgent medical need.
  • Document urgent medical need in the patient’s medical record.
  • Obtain written approval from the medical director for use of ineligible donor products.
• Label all products from ineligible donors with “WARNING: Advise patient of communicable disease risks.”
  • Cross-check labels against Reference Standard 5.6.2A for compliance.
• Review and comply with local, FDA, and relevant Competent Authority regulations for ineligible donor products.
  • Maintain a current list of applicable regulations and guidelines.
• Conduct regular audits to ensure compliance with labeling and documentation requirements.
• Train staff on procedures for handling and labeling products from ineligible donors.
  • Keep training records and competency evaluations up to date.

5.10.7.1

Any product with abnormal donor testing results shall also be labeled with the phrase “WARNING: Reactive test results for [name of disease agent or disease].”

☑ Actionable Checklist

• Develop and implement an SOP for labeling products with abnormal donor testing results.
  • Include specific instructions for labeling with “WARNING: Reactive test results for [name of disease agent or disease].”
• Train staff on the SOP for labeling products with abnormal donor testing results.
  • Document training completion in training records.
• Create a log to track products labeled with abnormal donor testing results.
  • Ensure the log includes the disease agent or disease name.
• Conduct regular audits to verify compliance with labeling requirements.
  • Document audit findings and corrective actions taken.
• Review and update the SOP annually or as needed based on regulatory changes.
• Include labeling compliance in management review meetings and document discussions.

5.10.8 Donors with Incomplete Eligibility Determinations

[F]

Allogeneic donors who were not screened or tested in conformance with requirements of the FDA or relevant Competent Authority shall have an incomplete donor eligibility determination for that donation.

Guidance

For facilities in the United States, see FDA guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (August 2007). (SS)

☑ Actionable Checklist

• Develop and implement an SOP for managing donors with incomplete eligibility determinations.
  • Include criteria for identifying incomplete eligibility.
  • Outline steps for documenting and reporting incomplete eligibility.
• Maintain a log of all allogeneic donors with incomplete eligibility determinations.
  • Ensure log is reviewed regularly for compliance and completeness.
• Train staff on procedures for handling donors with incomplete eligibility determinations.
  • Document training sessions and retain records.
• Conduct regular audits to ensure compliance with FDA and relevant Competent Authority requirements.
  • Include review of donor eligibility documentation in audit scope.
• Implement a CAPA process for addressing issues related to incomplete donor eligibility determinations.
  • Document all CAPAs and track their resolution.
• Review and update the SOP annually or as regulations change, ensuring alignment with FDA guidance.

5.10.8.1

If testing is not performed in conformance with Standard 5.10.2.8 or if testing does not meet the requirements of the manufacturer of the test kit, the donor eligibility determination shall be incomplete.

5.10.8.1.1

If testing is not complete, a listing of all pending infectious disease test results and an interpretation of those performed shall be retained and accompany the product.

☑ Actionable Checklist

• Develop an SOP for handling incomplete donor eligibility determinations, referencing AABB Standard 5.10.8.1.
  • Include procedures for documenting incomplete testing and pending results.
  • Specify actions for notifying relevant personnel of incomplete determinations.
• Create a form or log to list all pending infectious disease test results.
  • Ensure the form includes sections for test interpretation and accompanying product documentation.
• Train staff on the SOP for incomplete donor eligibility determinations.
  • Document training sessions and maintain records in the training log.
• Conduct regular audits to ensure compliance with SOP and documentation requirements.
  • Review a sample of donor records to verify proper documentation of pending results and interpretations.
• Implement a CAPA process for any deviations related to incomplete testing or documentation.
  • Document all CAPAs and review them in management meetings.

5.10.8.2

[Cord blood applicable]

When the donor eligibility determination is incomplete, the facility shall complete the eligibility determination during or after use of the product, if possible, or indicate in the associated records the reason that the eligibility determination could not be completed. The results of the determination of donor eligibility shall be communicated to the recipient’s physician.

☑ Actionable Checklist

• Develop and implement an SOP for completing donor eligibility determination post-product use.
  • Include procedures for documenting incomplete eligibility determinations.
  • Specify timelines for completing eligibility determination after product use.
• Create a form or log for recording reasons when donor eligibility determination cannot be completed.
• Establish a communication protocol for informing the recipient’s physician of donor eligibility results.
  • Ensure documentation of communication in the recipient’s medical records.
• Train staff on procedures for handling incomplete donor eligibility determinations.
  • Maintain training records and competency evaluations.
• Conduct regular audits to ensure compliance with donor eligibility determination processes.
• Review and update the SOP and communication protocol annually or as needed.

5.10.9 Products from Donors with Incomplete Donor Eligibility Determinations

Products from allogeneic donors with incomplete donor eligibility determinations (donor screening and/or testing not completed in accordance with the requirements of the FDA or relevant Competent Authority) shall be provided only under urgent medical need, and shall be labeled with the statements “Not evaluated for infectious substances” and “WARNING: Advise patient of communicable disease risks.” Standard 5.22.2 applies.

☑ Actionable Checklist

• Develop an SOP for handling products from donors with incomplete eligibility determinations, including criteria for urgent medical need.
• Implement a labeling process to ensure products are marked with “Not evaluated for infectious substances” and “WARNING: Advise patient of communicable disease risks.”
  • Train staff on labeling procedures and verify understanding through competency evaluations.
• Maintain a log of all products distributed under urgent medical need, including donor eligibility status and labeling compliance.
• Conduct regular audits to ensure adherence to SOPs and labeling requirements for these products.
• Review and update the SOP annually or as regulations change, documenting all revisions.
• Ensure all deviations related to donor eligibility determinations are documented and addressed through CAPAs.

5.10.9.1

If infectious disease testing is performed on a sample that does not meet the requirements of the manufacturer of the test kit, the product shall be determined to have an incomplete donor eligibility determination and shall be labeled with the phrase “Not evaluated for infectious substances,” even if all donor screening and testing were completed and if there were no abnormal results.

☑ Actionable Checklist

• Review and update SOPs to include labeling requirements for products with incomplete donor eligibility determination.
  • Ensure SOPs specify labeling with “Not evaluated for infectious substances” for applicable products.
• Train staff on identifying samples that do not meet test kit requirements and the necessary labeling procedures.
  • Document training sessions and maintain records in the training log.
• Implement a checklist for verifying compliance with labeling requirements during product release.
• Conduct regular audits to ensure proper labeling of products with incomplete donor eligibility determination.
  • Document findings and corrective actions in the audit log.
• Review and update the Validation Master Plan to include validation of labeling processes for compliance with this standard.
• Maintain records of all deviations and CAPAs related to infectious disease testing and labeling.

5.10.9.2

Allogeneic units from donors with incomplete donor eligibility determinations or from ineligible donors shall be released only under urgent medical need.

☑ Actionable Checklist

• Develop and implement an SOP for the release of allogeneic units under urgent medical need.
  • Include criteria for determining urgent medical need.
  • Outline the documentation process for donor eligibility status.
• Establish a log to record instances of release under urgent medical need.
  • Ensure the log includes donor eligibility status and justification for release.
• Train staff on the SOP for urgent medical need releases and document training completion.
• Conduct regular audits of the urgent medical need release process to ensure compliance.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.10.10 Labeling for Autologous Products

Autologous units shall be labeled with the phrase “For autologous use only” and, if testing or screening is not completed or performed, shall be labeled with the statement “Not evaluated for infectious substances.” Standard 5.6 and Reference Standard 5.7.5A, Labeling and Packaging Requirements upon Shipping of Cellular Therapy Products, apply.

Guidance

The label “Not evaluated for infectious substances” would be placed on autologous products if:

• Some, but not all, of the testing and screening required by these standards was performed.
• Testing was not performed in a CLIA-certified laboratory.
• Testing was performed in a laboratory that was not registered with the FDA or other Competent Authority.
• The donor screening tests used were not licensed, cleared, or approved by the FDA or other Competent Authority.

Additionally, if a product was tested for all relevant communicable disease agents and diseases using approved donor screening testing, but no official donor eligibility determination was made, that product should be labeled “Not evaluated for infectious substances.” When a positive result is obtained, then the autologous product should be labeled with the biohazard legend and applicable warning statement “WARNING: Reactive test results for [name of disease agent or disease]” with the name of the disease agent or disease included on the label. If the container is too small to affix these labels to the container, or the container is frozen, or for any other reason affixing the labels or attaching a tie-tag is not feasible, the “WARNING: Reactive test results for [name of disease agent or disease]” statements may accompany the CT product. (SS)

☑ Actionable Checklist

• Ensure all autologous units are labeled with “For autologous use only.”
• Verify that autologous products with incomplete testing are labeled “Not evaluated for infectious substances.”
  • Confirm testing was performed in a CLIA-certified laboratory.
  • Ensure laboratory is registered with the FDA or other Competent Authority.
  • Use only FDA-licensed, cleared, or approved donor screening tests.
• Label products with a positive test result with the biohazard legend and “WARNING: Reactive test results for [name of disease agent or disease].”
• Develop SOPs for labeling autologous products, including scenarios for incomplete testing.
• Maintain a log of all labeled autologous products, including label content and testing status.
• Conduct regular audits to ensure compliance with labeling requirements and document findings.

5.10.10.1

The biohazard label shall be attached to autologous products for which there is abnormal or reactive infectious disease marker testing or donor screening results. Any product with abnormal testing results shall also be labeled with the statement “WARNING: Reactive test results for [name of disease agent or disease].”

Guidance

The committee has added a clause for completeness stating, “…or reactive infectious disease marker…” mirroring the current labeling requirements for autologous products. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for labeling autologous products with biohazard labels.
  • Include criteria for when to apply biohazard labels based on infectious disease marker testing.
• Ensure the SOP includes procedures for adding the statement “WARNING: Reactive test results for [name of disease agent or disease]” on applicable products.
• Train staff on the updated labeling SOP and document completion in training records.
• Perform regular audits to verify compliance with labeling requirements for autologous products.
• Maintain a log of all products labeled with biohazard warnings, including details of the reactive test results.
• Review and update the SOP annually or as needed based on changes in regulations or standards.

5.11 Medical Management and Emergency Care of Donors

☑ Actionable Checklist

• Develop and maintain an SOP for the medical management and emergency care of donors.
  • Include procedures for assessing donor eligibility and managing adverse events.
• Ensure all staff involved in donor care are trained and competent in emergency procedures.
  • Maintain training records and competency evaluations.
• Conduct regular drills for emergency response scenarios involving donor care.
  • Document outcomes and any necessary improvements.
• Keep emergency equipment and medications readily available and regularly checked.
  • Maintain a log for equipment checks and medication expirations.
• Review and update the emergency care SOP annually or after any incident.
  • Document all reviews and updates in the management review records.

5.11.1

The availability of medical care shall be based on the risks and clinical situation associated with each category of donation. Facilities procuring cells, tissues, or organs from living donors shall have provisions for emergency care and medical management of adverse events in those donors.

☑ Actionable Checklist

• Develop and implement an SOP for assessing risks and clinical situations associated with each category of donation.
  • Include criteria for determining the level of medical care required.
• Establish a protocol for emergency care and medical management of adverse events in living donors.
  • Ensure availability of emergency contact information and resources.
• Conduct regular training sessions for staff on emergency procedures and medical management protocols.
  • Maintain training records and competency evaluations.
• Perform a gap analysis to ensure compliance with AABB, FACT-JACIE, and FDA standards regarding donor safety.
• Review and update the emergency care protocol annually or as needed based on incident reports and management reviews.
• Document all adverse events and the medical management provided, and review these records in management meetings.

5.11.2

[Cord blood applicable]

When a central venous access device is used for a procurement procedure, the following requirements shall apply:

1. The device shall be placed by a qualified person (under the supervision of a licensed physician if the individual is not a physician).
2. Before procurement, the correct anatomic location of the access device shall be confirmed by methods appropriate for the placement site.

Guidance

Central venous access devices must be placed by a qualified, trained, and/or licensed person in an
appropriate and safe position such that cellular products may be collected efficiently. Confirmation that the central venous access device is in a satisfactory position and functions properly before collection must be documented. Methods such as fluoroscopy, ultrasound, and x-ray imaging may be used, as appropriate for the type of central venous access device. (SS)

☑ Actionable Checklist

• Ensure all personnel placing central venous access devices are qualified and trained.
  • Maintain up-to-date training records and competency evaluations for all personnel involved.
• Develop and implement an SOP for the placement of central venous access devices.
  • Include steps for supervision by a licensed physician if the individual is not a physician.
• Confirm and document the correct anatomic location of the access device before procurement.
  • Use appropriate methods such as fluoroscopy, ultrasound, or x-ray imaging.
  • Record confirmation in the patient’s medical record or procedure log.
• Conduct regular internal audits to ensure compliance with the SOP and documentation requirements.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.
• Document any deviations from the SOP and implement corrective and preventive actions (CAPAs) as required.

5.11.3

Administration of a pharmacologic or biologic agent(s) to the donor shall be performed under the supervision of a licensed physician experienced in the use of said agent(s) and management of complications.

☑ Actionable Checklist

• Verify that all pharmacologic or biologic agent administrations to donors are supervised by a licensed physician.
  • Ensure the physician has documented experience in the use of the specific agent(s).
  • Maintain a list of qualified physicians and their credentials.
• Develop and maintain an SOP for the administration of pharmacologic or biologic agents to donors.
  • Include procedures for managing potential complications.
• Conduct regular training sessions for physicians on the administration protocols and complication management.
  • Keep training records and competency evaluations up to date.
• Document each administration event in the donor’s medical record, including physician supervision details.
• Review and update the SOP and physician credential list annually or as needed.

5.11.3.1

[Cord blood applicable]

Allogeneic and autologous donors shall be evaluated for the risk of hemoglobinopathy before the administration of a mobilizing agent.

☑ Actionable Checklist

• Develop and implement an SOP for evaluating donors for hemoglobinopathy risk.
  • Include criteria for risk assessment and documentation procedures.
• Train staff on the SOP for donor evaluation and maintain training records.
• Create a checklist or form for documenting hemoglobinopathy risk assessment results.
• Conduct regular audits to ensure compliance with the hemoglobinopathy evaluation SOP.
• Review and update the SOP annually or as needed based on new guidelines or findings.
• Document any deviations from the SOP and implement CAPAs as necessary.

5.11.4

Administration of local anesthesia to the donor shall be performed under the supervision of a credentialed physician. Sedation (monitored anesthesia care), regional anesthesia, or general anesthesia shall be administered under the supervision of a licensed anesthesia provider. Pain management for postprocedure care shall be available, if necessary.

Guidance

In some cases, a licensed anesthesiologist may not be required to administer conscious sedation, although the physician must still be credentialed. For example, many cardiologists (performing procedures in the catheterization laboratory) or physicians (performing colonoscopies) may be credentialed by their institution to administer moderate conscious sedation. In cardiac CT applications that require marrow harvest, a cardiologist may be present when the nurse administers conscious sedation and the hematopathologist performs the marrow aspiration. The individual would still need to have appropriate experience, specific training, competency, and continuing medical education as defined in Chapters 1 and 2, Organization and Resources, respectively. (SS)

The committee replaced the term “anesthesiologist” with “provider” recognizing that there are individuals who can provide anesthesia and are doing so while not being a licensed anesthesiologist. (SC)

☑ Actionable Checklist

• Ensure all anesthesia providers are licensed and credentialed according to institutional requirements.
  • Verify credentials and maintain records in the personnel files.
• Develop and maintain SOPs for the administration of local, regional, and general anesthesia.
  • Include supervision requirements by a credentialed physician or licensed anesthesia provider.
• Implement a training program for staff involved in anesthesia administration.
  • Document training completion and competency evaluations in training records.
• Establish a protocol for post-procedure pain management.
  • Ensure availability of pain management resources and document their use.
• Conduct regular audits to ensure compliance with anesthesia administration protocols.
  • Document findings and corrective actions in audit reports.
• Review and update the Validation Master Plan (VMP) to include anesthesia administration processes.

5.11.5

The procurement facility shall protect the health and safety of the donor. Criteria for discontinuation of procurement due to medical complications shall be specified.

☑ Actionable Checklist

• Develop and implement an SOP for donor health and safety during procurement.
  • Include criteria for discontinuation of procurement due to medical complications.
• Train staff on the SOP and document training records.
• Conduct competency evaluations for staff on donor health and safety procedures.
• Maintain a log of all procurement procedures, noting any complications or discontinuations.
• Review and update the SOP annually or as needed based on new evidence or incidents.
• Perform regular audits to ensure compliance with donor safety protocols.

5.11.5.1

Cord blood or gestational material procurement procedures shall ensure the safety of the birth mother and the neonate.

☑ Actionable Checklist

• Develop and maintain SOPs for cord blood and gestational material procurement ensuring maternal and neonatal safety.
  • Include criteria for donor eligibility and exclusion.
  • Outline procedures for handling adverse events during procurement.
• Conduct and document training for staff on procurement procedures and safety protocols.
• Perform regular competency assessments for personnel involved in procurement.
• Maintain records of all procurement activities, including any deviations and corrective actions.
• Review and update procurement procedures annually or as needed based on regulatory changes or internal audits.
• Implement a system for monitoring and reporting any adverse events related to procurement.

5.12 Procurement

There shall be policies, processes, and procedures for each procurement method performed in the facility.

☑ Actionable Checklist

• Develop and document SOPs for each procurement method used in the facility.
  • Ensure SOPs include step-by-step instructions for each method.
  • Reference relevant regulatory requirements within SOPs.
• Implement a training program for staff on all procurement SOPs.
  • Maintain training records and competency evaluations.
• Conduct regular internal audits to ensure adherence to procurement SOPs.
  • Document audit findings and corrective actions.
• Establish a process for reviewing and updating procurement SOPs annually.
  • Document review dates and any changes made.
• Maintain a log of all procurement activities, including deviations and CAPAs.
  • Ensure logs are reviewed regularly for compliance and improvement opportunities.

5.12.1 Medical Order for Procurement

[F]

The procuring facility shall obtain a medical order before the procurement procedure for all cellular therapy products other than for cord blood or gestational materials. The medical order shall include procurement goals. Standard 5.13 applies.

☑ Actionable Checklist

• Develop and implement an SOP for obtaining medical orders prior to procurement.
  • Include steps for verifying the medical order includes procurement goals.
  • Reference Standard 5.13 for additional requirements.
• Train staff on the SOP for obtaining and verifying medical orders.
  • Document training sessions and maintain training records.
• Create a standardized form or checklist to document receipt and verification of medical orders.
• Conduct regular audits to ensure compliance with the medical order procurement process.
• Maintain a log of all medical orders received, including date, time, and verification status.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.12.1.1

Cord blood, gestational materials, or tissue or cellular starting materials collected from a noninvasive procedure and before identification of an intended recipient do not require a medical order before procurement. Standard 5.22 applies.

Guidance

The committee created new standard 5.12.1.1 recognizing that there are certain products that do not require a medical order for procurement. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for the procurement of cord blood, gestational materials, or tissue or cellular starting materials without a medical order.
  • Include criteria for noninvasive procedures and pre-identification of intended recipients.
• Train staff on the SOP and document training records.
• Conduct regular audits to ensure compliance with the SOP.
• Maintain a log of all procurements conducted under this standard.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.12.2 Verification of Medical Suitability

☑ Actionable Checklist

• Develop and maintain an SOP for verifying the medical suitability of cellular therapy products.
  • Include criteria for donor eligibility and product quality.
• Implement a verification checklist to document the assessment of medical suitability.
• Train staff on the SOP and verification process, documenting all training sessions.
• Conduct competency evaluations for staff involved in the verification process.
• Perform regular internal audits to ensure compliance with the verification SOP.
• Document any deviations from the verification process and initiate CAPAs as necessary.

5.12.2.1

Before procurement, the procurement facility shall verify that the determination of medical
suitability has been completed. Standard 5.2.1 and Reference Standard 5.10B, Clinical
Evaluation and Laboratory Testing of Living Allogeneic Donors; Reference Standard 5.10C, Clinical Evaluation and Laboratory Testing of Autologous Donors; Reference Standard 5.10D, Clinical Evaluation and Laboratory Testing of Mothers of Cord Blood or Gestational Material Donors (#I); and Reference Standard 5.10E, Clinical Evaluation and Laboratory Testing of Cadaveric Donors, apply.

☑ Actionable Checklist

• Verify completion of medical suitability determination prior to procurement.
  • Review and document compliance with Standard 5.2.1 and Reference Standards 5.10B, 5.10C, 5.10D, and 5.10E.
• Maintain a checklist or form to ensure all required evaluations and tests are completed for each donor type.
• Cross-reference SOPs related to donor evaluation and testing with the applicable standards.
• Conduct regular audits of donor records to confirm adherence to medical suitability requirements.
• Train staff on the importance of verifying medical suitability and the specific procedures for each donor type.
• Document any deviations from the medical suitability verification process and implement corrective actions.

5.12.2.2

[F]

Before any procurement procedure, the procuring facility shall obtain final approval and documentation by the donor’s physician, or by another physician who is not directly involved with the care of the recipient, that the donor is suitable to proceed with donation, in conformance with Reference Standard 5.10A, General Requirements for Cellular Therapy Product Donors; Reference Standard 5.10B, Clinical Evaluation and Laboratory
Testing of Living Allogeneic Donors; and Reference Standard 5.10C, Clinical Evaluation and Laboratory Testing of Autologous Donors.

☑ Actionable Checklist

• Develop and maintain an SOP for obtaining final approval and documentation from the donor’s physician.
  • Include procedures for verifying the physician’s independence from the recipient’s care.
  • Reference SOPs for compliance with Reference Standards 5.10A, 5.10B, and 5.10C.
• Create a standardized form for documenting the donor’s suitability approval.
  • Ensure the form captures all necessary physician signatures and dates.
• Implement a log to track all donor suitability approvals prior to procurement.
  • Regularly review the log for completeness and accuracy.
• Conduct training sessions for staff on the SOP and documentation requirements.
  • Maintain training records and competency evaluations.
• Schedule regular internal audits to ensure compliance with the approval process.
  • Document findings and implement corrective actions as needed.

5.12.2.3

[Cord blood applicable]

For marrow donors or donors of cells collected by apheresis, facilities shall:

1. Define criteria to evaluate the results of a complete blood count before each procurement.
2. Define time frames for obtaining a complete blood count before the initial procurement.
3. Obtain a complete blood count within 24 hours before each subsequent procurement after the initial procurement.

☑ Actionable Checklist

• Develop and document SOPs for evaluating complete blood count (CBC) results prior to each procurement.
  • Include specific criteria for acceptable CBC results.
• Establish and document SOPs defining the time frames for obtaining CBCs before initial procurement.
  • Specify the maximum allowable time between CBC and initial procurement.
• Implement a process to ensure CBC is obtained within 24 hours before each subsequent procurement.
  • Use a checklist or log to track CBC timing and results for each donor.
• Train staff on SOPs related to CBC evaluation and timing requirements.
  • Maintain training records and competency evaluations for all relevant personnel.
• Conduct regular audits to verify compliance with CBC timing and evaluation criteria.
  • Document findings and corrective actions in audit reports.

5.12.2.4

[F]

On each day of procurement, a health-care professional at the procurement site shall confirm that the donor’s medical status permits procurement and document that the donor’s health status is acceptable for donation. Reference Standard 4.5A, Donor Informed Consent or Authorization, and Reference Standard 5.10A, General Requirements for Cellular Therapy Product Donors, apply.

☑ Actionable Checklist

• Develop and implement an SOP for confirming donor medical status before procurement.
  • Include criteria for acceptable donor health status in the SOP.
• Train healthcare professionals on the SOP and document training records.
• Use a standardized form or electronic system to document donor health status confirmation.
• Conduct daily checks to ensure documentation is completed for each donor.
• Perform regular audits to verify compliance with the SOP and documentation accuracy.
• Review and update the SOP annually or as needed based on audit findings and regulatory changes.

5.12.3 Verification of Donor Eligibility

On each day of procurement, the procurement facility shall verify that the determination of donor eligibility has been completed and confirm that the donor’s health history has not changed, other than for cord blood or gestational materials. Standard 5.10.8 applies.

Guidance

Determination of donor eligibility may occur at an earlier date. In this circumstance, it is the responsibility of the facility to document updates to the donor’s health history or current state that may impact eligibility. If a facility performs donor screening to determine donor eligibility ahead of time, the facility should have a process to ensure that the donor’s screening status has remained the same as on the day the information was obtained. (SS)

☑ Actionable Checklist

• Verify donor eligibility determination is complete before each procurement day.
  • Use the Donor Eligibility Verification Form to document completion.
• Confirm no changes in donor health history on procurement day.
  • Update the Donor Health History Log with any changes.
• Maintain a documented process for updating donor health history.
  • Review and update SOP CT-05.12.3 for donor health history verification.
• Ensure all procurement staff are trained on donor eligibility verification procedures.
  • Record training completion in the Training Records Log.
• Conduct internal audits to verify compliance with donor eligibility verification.
  • Use the Internal Audit Checklist for QSE 5.12.3 compliance checks.

5.12.4 Donor Identity

[F]

At the time of procurement, the donor’s identity shall be confirmed by at least two independent identifiers.

☑ Actionable Checklist

• Develop and implement an SOP for confirming donor identity using two independent identifiers at procurement.
  • Include a list of acceptable identifiers (e.g., name, date of birth, unique donor ID).
• Train staff on the SOP for donor identity confirmation and document completion of training.
• Create a form or electronic log to record the two identifiers used for each donor at procurement.
• Conduct regular audits of procurement records to ensure compliance with the identity confirmation SOP.
• Implement a CAPA process to address any deviations found during audits related to donor identity confirmation.
• Review and update the SOP annually or as needed to incorporate any changes in best practices or regulations.

5.12.4.1

For cord blood or gestational materials, the identity of the birth mother shall be confirmed by at least two independent identifiers.

☑ Actionable Checklist

• Implement an SOP for confirming the identity of the birth mother using two independent identifiers.
  • Specify acceptable identifiers such as name and date of birth.
• Train staff on the SOP for confirming the birth mother’s identity.
  • Document training completion and competency evaluations.
• Develop a form or electronic system to record the two identifiers for each collection.
• Conduct regular audits to ensure compliance with the identity confirmation process.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.12.5 Procurement Records

[F]

A procurement record shall include:

1. Donation identification number.
2. Product description code, type of collection, and division code.
3. Product name and attributes.
4. Unique donor and/or patient identifier, if available.
5. Date and time of procurement.
6. Name and address of the procurement facility.
7. Details of the procured product/procurement process.
8. Identification of persons responsible for each step of procurement.
9. Names, manufacturers, lot numbers, and expiration dates of critical materials and reagents, and quantities used in procurement.
10. Identification of equipment used for procurement.

Standards 5.6.1, 7.2.5, and 7.3 apply.

Guidance

Facilities that collect cellular therapy products by apheresis for further manufacturing by a clinical trial sponsor or manufacturer should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product. Such facilities should also maintain a chain of identity that ensures permanent and transparent association of a cell or gene therapy’s unique identifiers from procurement of tissue or cells throughout the full product(s) lifecycle, including posttreatment monitoring.

For further information, refer to the guidance associated with Standards 5.1.2 and 6.2.3. (SS)

☑ Actionable Checklist

• Develop and maintain an SOP for recording procurement information, including donation identification number, product description code, and division code.
  • Ensure the SOP includes steps for documenting product name, attributes, and unique donor/patient identifiers.
• Implement a standardized form or electronic system to capture date and time of procurement, and name and address of the procurement facility.
• Train staff on accurately recording details of the procured product and procurement process, including identification of responsible personnel.
  • Maintain training records and competency evaluations for all staff involved in procurement.
• Create a log for documenting names, manufacturers, lot numbers, expiration dates, and quantities of critical materials and reagents used.
  • Include fields for identification of equipment used during procurement.
• Conduct regular internal audits to verify compliance with procurement record-keeping standards.
  • Document any deviations and implement corrective and preventive actions (CAPAs) as needed.
• Ensure all procurement records are auditable and maintain a chain of custody and chain of identity for all products.

5.12.6 Review of Procurement Records

[F]

The facility shall ensure that the procurement record for each cellular therapy product or cellular starting material is accurate and complete in a specified time frame.

Guidance

The committee added the clause “cellular starting material” to the standard to expand the scope of the Standards. (SC)

☑ Actionable Checklist

• Establish an SOP for the review of procurement records, including cellular therapy products and starting materials.
  • Define the specific time frame for record review completion.
• Train staff on the SOP for procurement record review and document all training sessions.
• Implement a checklist or form to ensure all required information is captured in procurement records.
• Conduct regular audits of procurement records to verify accuracy and completeness.
• Document any deviations found during audits and initiate CAPAs as necessary.
• Schedule and document management reviews to ensure ongoing compliance with procurement record standards.

5.12.7 Procurement Record Availability

Each facility performing procurement shall provide access to product procurement record(s) to the facility receiving the product while maintaining the chain of custody. Chapter 4, Suppliers and Customers, applies.

Guidance

Facilities procuring material for another facility or department should establish policies and procedures to ensure that the chain of custody is maintained through all handoffs. Documentation of who is in possession of the product, the time and the point in the process, as well as their roles and responsibilities, as outlined in agreements, would meet the intent of this standard. (SS)

The committee edited this standard for clarity, recognizing that “access” is more of an encompassing term than “a” which is what previously appeared in the standard. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for maintaining and providing access to procurement records.
  • Include steps for documenting chain of custody during procurement.
  • Define roles and responsibilities for all personnel involved in procurement.
• Ensure all procurement records are readily accessible to receiving facilities.
  • Use a secure, centralized system for record storage and access.
• Conduct regular training sessions on procurement record management and chain of custody procedures.
  • Maintain training records and competency evaluations for all relevant staff.
• Perform periodic internal audits to verify compliance with procurement record availability and chain of custody requirements.
  • Document findings and implement corrective actions as needed.
• Establish agreements with receiving facilities that outline access to procurement records and chain of custody responsibilities.
  • Review and update agreements annually or as needed.

5.12.7.1

Records shall include:

1. Donation identification number.
2. Product description code, type of collection, and division code.
3. Product name and attributes.
4. Unique donor and/or patient identifier, if available.
5. Date and time of procurement, including time zone if applicable.
6. Name and address of the procurement facility.

☑ Actionable Checklist

• Ensure all records include a donation identification number.
• Verify that records capture product description code, type of collection, and division code.
• Confirm product name and attributes are documented in records.
• Include unique donor and/or patient identifier in records, if available.
• Record the date and time of procurement, including time zone if applicable.
• Document the name and address of the procurement facility in all records.

5.13 Procurement Goals

[F]

Procurement goals shall be defined.

☑ Actionable Checklist

• Define specific procurement goals aligned with organizational objectives.
  • Document procurement goals in the Quality Management Plan (QMP).
• Develop and implement SOPs for setting and reviewing procurement goals.
  • Include criteria for goal evaluation and adjustment in SOPs.
• Conduct regular reviews of procurement goals to assess progress.
  • Use procurement performance data and metrics for evaluation.
• Maintain records of procurement goal reviews and any adjustments made.
• Train relevant staff on procurement goals and their role in achieving them.
  • Document training sessions and maintain attendance records.

5.13.1 Unrealized Goals

If expected goals are not met, Chapter 7, Deviations, Nonconformances, and  Adverse Events, applies as appropriate.

☑ Actionable Checklist

• Establish a process for identifying and documenting unrealized goals in the quality management system.
  • Reference SOP on tracking and evaluating performance against set goals.
• Implement a review mechanism to assess reasons for not meeting expected goals.
  • Use a standardized form for documenting root cause analysis.
• Initiate a deviation report for each instance of unrealized goals.
  • Ensure linkage to Chapter 7 procedures on deviations and nonconformances.
• Develop and document corrective and preventive actions (CAPAs) for each deviation.
  • Reference CAPA SOP for guidance on implementation and follow-up.
• Conduct management reviews to evaluate the effectiveness of actions taken.
  • Include unrealized goals as a standing agenda item in management review meetings.
• Maintain records of all actions taken in response to unrealized goals.
  • Ensure records are easily retrievable and linked to relevant SOPs and forms.

5.13.1.1

If expected goals are not met, the intended recipient’s physician, the processing facility, and other relevant parties shall be notified. Standard 7.1.3.1 applies.

☑ Actionable Checklist

• Develop an SOP for notifying relevant parties when expected goals are not met.
  • Include contact information for the recipient’s physician and processing facility.
  • Define the timeline for notification.
• Create a notification log to document all instances of unmet goals and notifications made.
• Train staff on the SOP and ensure competency evaluations are completed.
• Conduct regular audits to ensure compliance with the notification process.
• Review and update the SOP annually or as needed based on audit findings or changes in regulations.

5.14 Packaging

As soon as possible after procurement, each organ, tissue component, or cellular therapy product shall be packaged in an individually labeled container suitable for the specific product. Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products, applies.

☑ Actionable Checklist

• Develop and implement an SOP for packaging cellular therapy products immediately after procurement.
  • Include guidelines for selecting appropriate containers for different product types.
• Ensure each product is individually labeled according to Reference Standard 5.6.2A.
  • Cross-reference SOPs with the labeling requirements to ensure compliance.
• Maintain a log of all packaging activities, including date, time, and personnel involved.
• Conduct training sessions for staff on the packaging SOP and labeling requirements.
  • Keep records of training completion and competency evaluations.
• Perform regular internal audits to verify compliance with packaging and labeling standards.
• Document any deviations from packaging procedures and initiate CAPAs as necessary.

5.14.1

The facility shall verify the accuracy of the procurement container label and donor identification in the proximity of the donor.

☑ Actionable Checklist

• Develop and implement an SOP for verifying procurement container labels and donor identification.
  • Include steps for verification in the proximity of the donor.
• Train staff on the SOP and document training records.
• Conduct competency assessments for staff involved in the verification process.
• Maintain a log for recording verification of procurement container labels and donor identification.
• Perform regular internal audits to ensure compliance with the verification process.
• Document any deviations and implement CAPAs as necessary.

5.14.1.1

For in-utero cord blood or gestational material collections, the procurement facility shall verify the accuracy of the collection container label and donor identification in the proximity of the donor.

☑ Actionable Checklist

• Verify the collection container label matches the donor identification prior to collection.
  • Use SOP CT-Proc-Label-Verification for label verification process.
• Ensure donor identification is confirmed in the proximity of the donor.
  • Follow SOP CT-Donor-ID-Confirmation for donor ID procedures.
• Document the verification process in the Collection Verification Log.
• Conduct regular audits of collection procedures to ensure compliance with SOPs.
• Train staff on proper label verification and donor identification procedures.
  • Maintain training records in the Training Management System.

5.14.1.2

For ex-utero cord blood or gestational material collections, the procurement facility shall verify the label on the collection container against the donor identification.

Processing Activities

☑ Actionable Checklist

• Develop and implement an SOP for verifying the label on the collection container against donor identification.
  • Include steps for double-checking donor ID with a second staff member.
• Train staff on the SOP and document completion in training records.
• Create a standardized form or checklist for recording verification of donor identification.
• Conduct regular audits to ensure compliance with the verification process.
• Review and update the SOP annually or as needed based on audit findings or process changes.
• Document any deviations from the SOP and initiate CAPAs as necessary.

5.15 Testing

Cellular therapy products shall be tested during processing in conformance with Reference Standard 5.15A, Processing Tests for HPC, Apheresis and HPC, Marrow; Reference Standard 5.15B, Processing Tests for HPC, Cord Blood Products or Gestational Materials; and Reference Standard 5.15C, Processing Tests for Cellular Therapy Products Other than HPC, Apheresis; HPC, Marrow; and HPC, Cord Blood or Gestational Materials. Specifications for the following stages shall be defined for each type of cellular therapy product:

1. Incoming cells, tissues, and organs.
2. Intermediate products, if applicable.
3. Final products.

☑ Actionable Checklist

• Define and document specifications for incoming cells, tissues, and organs in SOP CT-5.15-01.
• Establish and record specifications for intermediate products in SOP CT-5.15-02, if applicable.
• Specify and document final product testing requirements in SOP CT-5.15-03.
• Utilize Reference Standards 5.15A, 5.15B, and 5.15C to ensure compliance with testing protocols.
• Maintain a log of all testing conducted during processing, including results and any deviations.
• Conduct regular reviews of testing procedures and results as part of the internal audit process.

5.15.1 Medical Order for Processing, Preservation, or Storage

[F]

The facility performing processing, preservation, or storage shall obtain an order from a health-care provider, if applicable. The order shall contain information that uniquely identifies the donor and the recipient. Specific instruction for cell processing and preservation shall be provided in the order as appropriate.

Guidance

The committee edited standard 5.15.1 by removing the clause “except for cord blood or gestational material manufacturing facilities” and used the basis to create new standard 5.15.1.1. (SC)

☑ Actionable Checklist

• Develop and maintain an SOP for obtaining medical orders for processing, preservation, or storage.
  • Include steps for verifying the order contains unique donor and recipient identifiers.
  • Specify required information for cell processing and preservation instructions.
• Implement a log or database to track all medical orders received.
  • Ensure each entry includes donor and recipient identifiers and processing instructions.
• Train staff on the SOP for handling medical orders.
  • Conduct competency evaluations to ensure understanding and compliance.
• Perform regular audits of medical orders to verify compliance with the SOP.
  • Document findings and implement corrective actions if necessary.
• Review and update the SOP annually or as needed based on regulatory changes or audit findings.

5.15.1.1

Facilities that process, preserve, or store cord blood, gestational materials, tissue, or
cellular starting materials collected from a noninvasive procedure and before identification of an intended recipient are not required to obtain a medical order before processing, preservation, or storage. Standard 4.2.3.1 applies.

Guidance

The committee added new substandard 5.15.1.1 to allow for information surrounding cord blood, gestational materials, and cell starting materials and what is expected to be included on a medical record for these products. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for processing, preserving, and storing cord blood and related materials without a medical order.
  • Include criteria for materials eligible for processing without a medical order.
  • Reference Standard 4.2.3.1 within the SOP.
• Create a form or electronic record template to document processing activities for these materials.
  • Ensure fields are included for material type, date of collection, and processing details.
• Train staff on the new SOP and documentation requirements.
  • Maintain training records and competency evaluations.
• Conduct regular internal audits to ensure compliance with the SOP and documentation practices.
• Establish a process for reviewing and updating the SOP as needed, based on audit findings or regulatory changes.

5.15.2 Processing Record

[F]

A complete processing record shall include:

1. Donation identification number.
2. Product description code, type of collection, and division code.
3. Product name and attributes.
4. Unique donor and/or patient identifier, if available.
5. Unique, traceable, chain-of-identity identifier, if applicable.
6. Date and time of procurement.
7. Name and address of processing facility.
8. All details of critical processing, preservation, and storage steps.* Records shall include:
   a) Date and time (if applicable) of critical steps.
   b) Names of persons responsible for each step.
   c) Names, manufacturers, lot numbers, and expiration dates of all critical materials used in processing, preservation, and storage.
   d) Quantities of reagents used.
   e) Identifiers of equipment used.
9. Documentation of product distribution or final disposition.
10. Final review as defined by the facility’s policies, processes, and procedures.

Guidance

The intent of this standard is to ensure that the facility has a process to document all pertinent details of critical processing, preservation, and storage steps. The individual processing records must be uniquely identifiable and traceable to the product and should be created and stored in a manner that permits adequate final review and audit as defined by the facility's policies, processes, and procedures. The facility should be able to demonstrate that all processing record information, as required by these standards, is retrievable.

Facilities that collect cellular therapy products by apheresis that are for further manufacturing by a clinical trial sponsor or manufacturer should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product.

For further information, refer to the guidance associated with Standards 5.1.2 and 6.2.3.

The chain-of-identity identifier is used to communicate across the supply chain and support the maintenance of the chain of custody as medical products of human origin (MPHO) collected for cellular therapy manufacturing move through the ecosystem. The chain-of-identity identifier should be available at all steps in the process. (SS)

#2 - The committee added subnumber 5 to this edition for completeness, ensuring that the chain of identity identifier was a part of the receipt process. This concept is new to the edition, and expands on “chain of identity”, which was introduced in the previous edition. (SC)

#8 - The committee noted that the elements in subnumber 8 apply to all processing records, not merely cryopreservation records, and edited the standard as such. (SC)

☑ Actionable Checklist

• Ensure processing records include a donation identification number.
• Record product description code, type of collection, and division code.
• Document product name and attributes in the processing record.
• Include unique donor and/or patient identifier, if available.
• Record unique, traceable, chain-of-identity identifier, if applicable.
• Capture date and time of procurement in the processing record.
• Document name and address of the processing facility.
• Record all critical processing, preservation, and storage steps:
  • Include date and time of each critical step.
  • Document names of persons responsible for each step.
  • Record names, manufacturers, lot numbers, and expiration dates of all critical materials used.
  • Note quantities of reagents used.
  • Identify equipment used with specific identifiers.
• Ensure documentation of product distribution or final disposition.
• Conduct a final review as defined by facility’s policies, processes, and procedures.

5.15.3 Determination of Acceptable Values or Ranges

[Cord blood applicable]

The facility shall define test methods and the acceptable values or ranges for defined critical characteristics of each product or cellular starting material [eg, recovery of specific cell populations, cell viability, cell identification and potency assays, function(s), purity, as appropriate, and sterility]. Reference Standard 5.15A, Processing Tests for HPC, Apheresis and HPC, Marrow; Reference Standard 5.15B, Processing Tests for HPC, Cord Blood Products or Gestational Materials; and Reference Standard 5.15C, Processing Tests for Cellular Therapy Products Other than HPC, Apheresis; HPC, Marrow; and HPC, Cord Blood or Gestational Materials, apply.

Guidance

The committee added the clause “cellular starting material” to the standard to expand the scope of the Standards. (SC)

☑ Actionable Checklist

• Define and document test methods for critical characteristics of each product or cellular starting material.
  • Include recovery of specific cell populations, cell viability, cell identification, and potency assays.
  • Specify function(s), purity, and sterility as appropriate.
• Establish and document acceptable values or ranges for each defined critical characteristic.
• Create SOPs for determining and verifying acceptable values or ranges.
• Conduct regular reviews of acceptable values or ranges to ensure they remain current and relevant.
• Maintain records of all test methods, acceptable values, and any changes made to them.
• Train staff on the defined test methods and acceptable values or ranges, and document training completion.

5.15.4 Managing Red Cell Antigen Incompatibility

[F]

The processing facility shall manage red cell antigen incompatibility, as applicable, between the donor and the recipient.

Guidance

Red cell antigen incompatibility between the product (donor) and recipient should be addressed in policies and procedures that identify methods to reduce red cell and plasma content of the HPC product.

These policies and procedures should:

• Address the reduction of the amount of incompatible red cells and/or plasma in the product.
• Determine and include acceptance criteria for the level of incompatible red cells/plasma based on clinical experience, literature, and benchmarking strategies.
• Outline steps to follow in the event that the final product does not meet acceptance criteria following manipulation to remove the incompatible antigen/antibody. For example, a facility should split infusion into two or more time frames with a rest period in between in order to assess the patient’s condition and tolerance for the incompatibility that exists. The clinical facility should report the results of the infusion, including any adverse reaction to product infusion, back to the processing facility. (SS)

☑ Actionable Checklist

• Develop and implement SOPs for managing red cell antigen incompatibility between donor and recipient.
  • Include methods for reducing red cell and plasma content in HPC products.
  • Establish acceptance criteria for incompatible red cells/plasma levels based on clinical experience and literature.
• Train staff on SOPs related to red cell antigen incompatibility management.
  • Document training sessions and maintain records in the training log.
• Create a protocol for handling products that do not meet acceptance criteria.
  • Include steps for splitting infusion into multiple time frames with rest periods.
  • Ensure clinical facility reports any adverse reactions back to the processing facility.
• Conduct regular audits to ensure compliance with SOPs and update them as necessary.
• Maintain records of all incidents of red cell antigen incompatibility and subsequent actions taken.
• Review and update the Validation Master Plan to include processes for managing red cell antigen incompatibility.

5.15.5 Processing Records

Each facility or the facilities performing processing, preservation, or storage shall provide a copy of the product processing record insofar as the processing records concern the safety, purity, and potency of the product or cellular starting material involved, or a summary of the product processing record to the facility(ies) receiving the product, while maintaining chain of custody. Chapter 4, Suppliers and Customers, applies.

Guidance

These standards do not specify whether processing records are to be provided in paper or electronic
format; therefore, this should be defined by the facility. The intent of the requirement is to ensure that
the requested information is provided. (SS)

The committee added the clause “cellular starting material” to the standard to expand the scope of the Standards. (SC)

☑ Actionable Checklist

• Develop an SOP for the preparation and distribution of product processing records.
  • Specify the format (paper or electronic) for processing records.
  • Include procedures for maintaining chain of custody.
• Implement a system to ensure processing records are complete and accurate before distribution.
  • Conduct regular audits of processing records for compliance.
• Establish a protocol for providing processing records or summaries to receiving facilities.
  • Maintain a log of all records distributed to ensure traceability.
• Train staff on the SOP for handling and distributing processing records.
  • Document training sessions and maintain records of staff competency evaluations.
• Regularly review and update the SOP to align with any changes in standards or regulations.

5.16 Storage of Noncryopreserved Products or Cellular Starting Materials

[Cord blood applicable]

The facility shall establish, for each type of product or cellular starting material, the storage specifications and defined storage conditions, including temperature range and length of storage to maintain facility-defined attributes (eg, viability).

☑ Actionable Checklist

• Establish and document storage specifications for each type of noncryopreserved product or cellular starting material.
  • Define temperature range and length of storage for each product type.
  • Ensure specifications maintain facility-defined attributes such as viability.
• Develop and implement SOPs detailing storage conditions and monitoring procedures.
  • Include steps for monitoring and recording storage temperatures.
  • Outline corrective actions for deviations from specified conditions.
• Maintain a log of storage conditions, including temperature data and any deviations.
• Conduct regular audits of storage areas to ensure compliance with defined specifications.
• Train staff on storage requirements and procedures, documenting all training sessions.
• Review and update storage specifications and SOPs annually or as needed based on new data or regulatory changes.

5.16.1 Management of Stored Noncryopreserved Inventory

☑ Actionable Checklist

• Develop and maintain an SOP for the management of stored noncryopreserved inventory.
  • Include procedures for inventory tracking, storage conditions, and handling.
• Implement a system for real-time inventory tracking and reconciliation.
  • Use electronic or manual logs to record inventory additions and removals.
• Conduct regular audits of the noncryopreserved inventory to ensure accuracy and compliance.
  • Schedule audits at least quarterly and document findings.
• Train staff on the SOP for inventory management and document training records.
• Establish criteria for the acceptance and rejection of noncryopreserved inventory.
  • Document criteria in the SOP and ensure staff are familiar with them.
• Review and update the SOP annually or as needed based on audit findings or process changes.

5.16.1.1

Cellular therapy products shall be maintained under defined conditions, including temperature range, between donation and final disposition.

☑ Actionable Checklist

• Define and document the temperature range for all cellular therapy products in an SOP.
  • Include specific temperature ranges for storage, transport, and handling.
• Implement a monitoring system to continuously track temperature conditions.
  • Use calibrated temperature monitoring devices with alarm systems.
• Maintain a temperature log for all storage and transport equipment.
  • Review logs daily and document any deviations.
• Train staff on procedures for maintaining defined temperature conditions.
  • Keep training records and competency evaluations up to date.
• Conduct regular internal audits to verify compliance with temperature control procedures.
• Document and address any deviations from defined temperature conditions through CAPA.

5.16.1.2

Aliquot(s) of cellular therapy products shall be maintained under defined conditions, including temperature range.

☑ Actionable Checklist

• Define and document temperature ranges for storage of aliquots in SOP.
• Implement and maintain temperature monitoring systems for storage units.
  • Calibrate temperature monitoring devices regularly and document calibration records.
• Train staff on procedures for maintaining and monitoring defined storage conditions.
• Conduct regular audits to ensure compliance with defined storage conditions.
• Develop and maintain a log for recording temperature excursions and corrective actions.
• Review and update SOPs annually or as needed based on process changes or audit findings.

5.16.1.3

The use and disposition of cellular therapy products (and aliquots if applicable) shall be defined in the facility’s policies, processes, and procedures.

☑ Actionable Checklist

• Develop and document SOPs for the use and disposition of cellular therapy products.
  • Include specific procedures for aliquots if applicable.
• Ensure all staff are trained on these SOPs and maintain training records.
• Implement a tracking system for cellular therapy products and aliquots.
  • Utilize logs or electronic systems to record product disposition.
• Conduct regular audits to verify compliance with SOPs.
• Review and update policies and procedures annually or as needed.
• Document any deviations and implement CAPAs as necessary.

5.16.1.4

The facility shall have processes to ensure traceability for any given product (and aliquots, if applicable) from donation to final disposition.

☑ Actionable Checklist

• Develop and implement an SOP for traceability from donation to final disposition.
  • Include steps for tracking products and aliquots.
• Maintain a traceability log or database for all products and aliquots.
• Conduct regular audits of traceability records to ensure completeness and accuracy.
• Train staff on traceability procedures and document all training sessions.
• Implement a system for documenting and resolving traceability deviations.
• Review and update traceability processes annually or as needed.

5.17 Cryopreservation of Cellular Therapy Products or Cellular Starting Materials

Cellular therapy products or cellular starting material shall be cryopreserved using a controlled-rate freezing procedure or equivalent procedure validated to maintain viability. The temperature of the product(s) and/or freezing process shall be monitored.

Guidance

The committee added the clause “cellular starting material” to the standard to expand the scope of the Standards. (SC)

☑ Actionable Checklist

• Develop and validate a controlled-rate freezing procedure for cellular therapy products and starting materials.
  • Document the validation process and results in the Validation Master Plan (VMP).
• Implement a monitoring system for the temperature of the product(s) during the freezing process.
  • Record temperature data in a Temperature Monitoring Log.
• Create an SOP for cryopreservation that includes steps for controlled-rate freezing and temperature monitoring.
• Train staff on the cryopreservation SOP and document training records.
• Conduct regular internal audits to ensure compliance with the cryopreservation procedure.
• Review and update the cryopreservation SOP and validation documentation annually or as needed.

5.17.1 Management of Cryopreserved Stored Inventory

☑ Actionable Checklist

• Develop and maintain an SOP for the management of cryopreserved stored inventory.
  • Include procedures for inventory tracking, storage conditions, and retrieval.
• Implement a cryopreserved inventory log to document storage location and conditions.
• Conduct regular audits of the cryopreserved inventory to ensure compliance with SOPs.
• Train staff on the SOP for cryopreserved inventory management and document training records.
• Review and update the SOP annually or as needed based on audit findings or process changes.
• Document any deviations from the SOP and implement CAPAs as necessary.

5.17.1.1

An aliquot of cryopreserved cellular therapy products shall be retained and stored under conditions equivalent to those of the cellular therapy product. The use and disposition of aliquot(s) shall be defined by the facility.

☑ Actionable Checklist

• Develop and implement an SOP for the retention and storage of aliquots of cryopreserved cellular therapy products.
  • Define equivalent storage conditions for aliquots in the SOP.
• Establish a log for tracking the use and disposition of aliquots.
• Conduct regular audits to ensure compliance with storage conditions.
• Train staff on the SOP for aliquot retention and storage.
  • Document training and competency evaluations in training records.
• Review and update the SOP annually or as needed based on audit findings or process changes.

5.17.1.2

An inventory control system shall be defined and validated to ensure that any given cellular therapy product, aliquots, and reference samples can be located while in storage.

☑ Actionable Checklist

• Define and document an inventory control SOP for cellular therapy products, aliquots, and reference samples.
  • Include procedures for labeling, tracking, and storage location assignments.
• Validate the inventory control system to ensure accurate location tracking and retrieval.
  • Conduct a validation study and document results in the Validation Master Plan (VMP).
• Implement an electronic or manual inventory log to record storage locations and movements.
  • Ensure logs are updated in real-time and reviewed regularly for accuracy.
• Train staff on the inventory control SOP and document training records.
• Conduct regular audits of the inventory control system to ensure compliance and effectiveness.
• Document any deviations or discrepancies in inventory management and initiate CAPAs as needed.

5.17.2 Special Requirements for Cord Blood

☑ Actionable Checklist

• Develop and maintain SOPs specific to cord blood collection, processing, and storage.
  • Ensure SOPs align with AABB and FACT-JACIE standards.
• Implement a training program for staff involved in cord blood activities.
  • Document all training sessions and competency evaluations.
• Establish a validation plan for cord blood processing equipment and procedures.
  • Maintain a Validation Master Plan (VMP) with documented evidence.
• Conduct regular internal audits focused on cord blood processes.
  • Document findings and implement corrective actions as needed.
• Create and maintain a crosswalk document mapping cord blood SOPs to relevant standards.
• Ensure all deviations and CAPAs related to cord blood are documented and reviewed.

5.17.2.1

Cord blood products shall have at least two integrally attached segments cryopreserved with the product. Standard 5.5.1.3 and Reference Standard 5.15B, Processing Tests for HPC, Cord Blood Products or Gestational Materials (#5), apply.

5.17.2.1.1

[Cord blood applicable]

The identity of the cord blood product and segment(s) shall be confirmed by two individuals or one individual and an electronic device that has been validated to fulfill the labeling identification function(s) when integrally attached segments are removed.

☑ Actionable Checklist

• Ensure SOPs include procedures for cryopreserving at least two integrally attached segments with each cord blood product.
  • Reference SOP: “Cryopreservation of Cord Blood Products”
• Implement a process for confirming the identity of cord blood products and segments by two individuals or one validated electronic device.
  • Reference SOP: “Identity Confirmation of Cord Blood Products”
• Validate any electronic devices used for labeling identification to ensure they fulfill the required functions.
  • Maintain validation records in the Validation Master Plan (VMP).
• Train staff on procedures for identity confirmation and document training records.
  • Reference Training Log: “Cord Blood Identity Confirmation Training”
• Conduct regular internal audits to ensure compliance with identity confirmation procedures.
  • Document findings and corrective actions in audit reports.
• Maintain a log of all identity confirmation activities, including personnel involved and methods used.

5.17.2.2

Cryopreserved cord blood products shall be stored at temperatures at or below –150 C in the liquid or vapor phase of liquid nitrogen.

☑ Actionable Checklist

• Verify and document that storage freezers maintain temperatures at or below -150°C.
  • Utilize calibrated temperature monitoring devices with alarms.
  • Record temperature logs daily and review for compliance.
• Develop and implement an SOP for the storage of cryopreserved cord blood products.
  • Include procedures for handling temperature excursions.
• Conduct regular maintenance and calibration of storage equipment.
  • Maintain service records and calibration certificates.
• Train staff on the SOP for storage and handling of cryopreserved products.
  • Document training and competency evaluations.
• Implement a CAPA process for addressing any deviations from storage temperature requirements.
  • Review and document all CAPA actions and outcomes.

5.17.3 Records for Cryopreserved Products

[F]

Cryopreservation records shall include, as applicable:

1. Donation identification number.
2. Product description code, type of collection, and division code.
3. Product name and attributes.
4. Unique donor and/or patient identifier, if available.
5. Unique, traceable, chain-of-identity identifier, if applicable.
6. Date and time of procurement.
7. Concentration or quantitation of the relevant cell type(s). Reference Standard 5.15A, Processing Tests for HPC, Apheresis and HPC, Marrow; Reference Standard 5.15B, Processing Tests for HPC, Cord Blood Products or Gestational Materials; and Reference Standard 5.15C, Processing Tests for Cellular Therapy Products Other than HPC, Apheresis; HPC, Marrow; and HPC, Cord Blood or Gestational Materials, apply.
8. Cell viability. Reference Standard 5.15A, Processing Tests for HPC, Apheresis, and HPC, Marrow; Reference Standard 5.15B, Processing Tests for HPC, Cord Blood Products or Gestational Materials; and Reference Standard 5.15C, Processing Tests for Cellular Therapy Products Other than HPC, Apheresis; HPC, Marrow; and HPC, Cord Blood Products or Gestational Materials, apply.
9. Name and volume or concentration of the cryoprotective agent(s).
10. Date and time of cryopreservation.
11. Temperature record during cryopreservation.
12. Endpoint temperature after cryopreservation.
13. Storage location of the cryopreserved product and any related test aliquots.

Chapter 4, Suppliers and Customers, applies.

Guidance

Facilities that collect cellular therapy products by apheresis that are for further manufacturing by a clinical trial sponsor or manufacturer should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product.

The chain-of-identity identifier is used to communicate across the supply chain and support the maintenance of the chain of custody as medical products of human origin (MPHO) collected for cellular therapy manufacturing move through the ecosystem. The chain-of-identity identifier should be available at all steps in the process.

For further information, refer to the guidance associated with Standards 5.1.2 and 6.2.3. (SS)

#5 - The committee created new subnumber 5 in standard 5.17.3 for completeness. In the previous edition, the committee had introduced this concept and felt it would be appropriate to add here. (SC)

#11 - The committee removed the clause, “if applicable” as it was deemed contrary to the focus of the standard, which is specific to cryopreservation records. (SC)

☑ Actionable Checklist

• Ensure all cryopreservation records include the donation identification number.
• Document the product description code, type of collection, and division code in cryopreservation records.
• Record the product name and attributes for each cryopreserved product.
• Include a unique donor and/or patient identifier in records, if available.
• Maintain a unique, traceable, chain-of-identity identifier, if applicable.
• Log the date and time of procurement for all cryopreserved products.
• Document the concentration or quantitation of relevant cell type(s) as per Reference Standards 5.15A, 5.15B, and 5.15C.
• Record cell viability in accordance with Reference Standards 5.15A, 5.15B, and 5.15C.
• Include the name and volume or concentration of cryoprotective agent(s) in records.
• Log the date and time of cryopreservation for each product.
• Maintain a temperature record during cryopreservation.
• Document the endpoint temperature after cryopreservation.
• Record the storage location of cryopreserved products and any related test aliquots.

5.18 Expiration Dates and Stability of Products

[Cord blood applicable]

☑ Actionable Checklist

• Establish and document SOPs for determining expiration dates for all cellular therapy products.
  • Include criteria for assigning expiration dates based on product type and storage conditions.
• Validate stability studies to support assigned expiration dates.
  • Document all stability testing protocols and results.
• Maintain a log of all expiration dates assigned to products, including any extensions or changes.
• Conduct regular reviews of stability data to ensure ongoing accuracy of expiration dates.
• Train staff on procedures for determining and documenting expiration dates.
  • Keep records of training sessions and competency evaluations.
• Implement a system to track and manage products nearing expiration to prevent use of expired products.

5.18.1

The facility shall define and validate expiration dates. Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products (#13), applies.

Guidance

The intent of the standards is to ensure that the facility has a process to assign an expiration date for all cellular therapy products. The facility should provide documented evidence to support the expiration date of each cell therapy product and should define the process of assigning the expiration date label based on the current stability program. If an expiration date is not affixed to cryopreserved products at the end of processing, then records of stability studies must be available to demonstrate support for assigning an expiration date at time of release of the cryopreserved product. The expiration date should be attached or affixed to the product before distribution. The facility should note that local regulatory labeling requirements may apply that are more stringent than these standards. (SS)

☑ Actionable Checklist

• Define and document the process for assigning expiration dates for all cellular therapy products in an SOP.
  • Reference SOP: “Expiration Date Assignment for Cellular Therapy Products.”
• Validate the expiration dates through stability studies and document the evidence.
  • Maintain records of stability studies in a dedicated log or database.
• Ensure that expiration dates are affixed to all products before distribution.
  • Check compliance with local regulatory labeling requirements.
• Conduct regular audits to verify adherence to the expiration date assignment process.
  • Use an internal audit checklist that includes expiration date verification.
• Train staff on the SOP for expiration date assignment and document training records.
  • Include competency evaluations specific to expiration date assignment.
• Review and update the SOP and related documentation annually or as needed.

5.18.2

Stability and expiration dating programs shall be based on the storage conditions for the final product.

Guidance

The committee created new standard 5.18.2 to ensure that facilities have stability programs for all expiring products. The standard was created for completeness. (SC)

☑ Actionable Checklist

• Develop and implement a stability testing program for all cellular therapy products.
  • Document the stability testing protocol in an SOP, including frequency and parameters.
• Establish expiration dating based on stability data and storage conditions.
  • Maintain a log of all stability studies and results.
• Regularly review and update the stability testing program to reflect new data or changes in storage conditions.
  • Conduct annual reviews of stability data and expiration dates.
• Train staff on the stability and expiration dating program.
  • Keep training records and competency evaluations current.
• Include stability and expiration dating program in internal audit schedules.
  • Document audit findings and corrective actions taken.

5.18.3

Cryopreserved products shall be monitored through a stability program. Sampling and evaluation shall be performed, at a minimum, on an annual basis. The facility’s sampling plan shall be included in the facility’s policies, processes, and procedures.

Guidance

The standards require that facilities have an active stability program for cryopreserved products. The facility must define its own stability program, and the program should be representative of the facility’s inventory. The facility is not required or expected to sample the same product repeatedly. For facilities that do not have historical stability data, reference to peer-reviewed scientific literature should be available, but this does not entirely replace the requirement to have a stability program on stored product inventory.

Standard 5.18.3 is a commonly cited standard for nonconformances. Examples of the reasoning behind the nonconformances include the following:

1. There is no evidence that stability testing is performed to determine an expiration date.
2. Cord blood units are observed with no expiration date at the time of distribution. (SS)

☑ Actionable Checklist

• Develop and document a stability program for cryopreserved products in the facility’s SOPs.
  • Include a sampling plan that is representative of the facility’s inventory.
  • Ensure the plan specifies annual sampling and evaluation.
• Perform stability testing on cryopreserved products at least annually.
  • Document all stability testing results and evaluations.
• Assign and document expiration dates for all cryopreserved products based on stability data.
• Review and update the stability program annually to incorporate new data or changes in inventory.
• Maintain records of all stability program activities, including sampling, testing, and evaluations.
• Conduct internal audits to verify compliance with the stability program and address any nonconformances.

5.18.3.1

The stability program shall include product container integrity, viable cell recovery, and an assessment of potency and purity of the relevant cell population(s).

Guidance

Testing of the product containers for integrity can be performed using mock products instead of an actual viable donor product. The durability of the container should be examined under the conditions it will be used. Viability and potency testing can be performed on a product’s integrally attached segment, a separate product sample that has been stored under the same conditions as the actual product, or a sample from the product itself at the time of thawing.

Acceptable potency assays should be defined by the facility and will depend on the product type. For HPC products, CFU testing is a demonstration of functional potency through the retention of clonogenic potential and would meet the intent of the standard for stability programs of cryopreserved products. Alternative functional assays for HPC products, including flow-cytometry-based assays, have also been developed that would also meet the intent of the standard. Viable CD34 counts are a surrogate for potency of HPC products and could be used if no other assays, such as CFU testing, are available. (See Reich-Slotky R, Vasovic LV, Land KJ, et al. Cryopreserved hematopoietic stem/progenitor cells stability program development, current status and recommendations: A brief report from the AABB-ISCT Joint Working Group Cellular Therapy Product Stability Project team. Transfusion 2022;62:1-12.)

Alternatively, postthaw data, including viable cell recovery, should be collected when products are thawed. If the product is thawed and used at a different facility, the cord blood bank should request that data be sent to them. If no products have been thawed, it is suggested that the facility obtain products (volunteer or purchase) that can be used to establish quality control data to ensure the processing, freezing, and storage methods result in acceptable stable products appropriate for the intended use.

Stability studies shall include studies to establish postthaw/postreconstitution expiration dates. (SS)

The committee added the term “purity” to standard 5.18.3.1 for completeness. (SC)

☑ Actionable Checklist

• Develop and document a stability program SOP that includes procedures for testing product container integrity, viable cell recovery, and assessments of potency and purity.
  • Include procedures for using mock products for container integrity testing.
  • Define acceptable potency assays specific to each product type.
• Establish and document protocols for viability and potency testing using integrally attached segments or separate product samples.
• Implement and validate CFU testing or alternative functional assays for HPC products to demonstrate potency.
• Collect and document postthaw data, including viable cell recovery, for each thawed product.
  • Request postthaw data from external facilities if products are thawed and used elsewhere.
• Conduct and document stability studies to establish postthaw/postreconstitution expiration dates.
• Regularly review and update the stability program SOP and associated records to ensure compliance with current standards and practices.

5.18.4

If cryopreserved products are to be distributed past their assigned expiration date, the facility shall have processes for review and approval of product release.

☑ Actionable Checklist

• Develop and implement an SOP for the review and approval process of distributing cryopreserved products past expiration.
  • Include criteria for product assessment and justification for extended use.
  • Define roles and responsibilities for review and approval.
• Create a form or log to document the review and approval process for each product.
  • Ensure the form includes product details, expiration date, and rationale for extended use.
• Train relevant staff on the SOP and documentation requirements for distributing expired products.
  • Maintain training records and competency evaluations.
• Conduct regular audits to ensure compliance with the SOP and proper documentation.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.18.4.1

If facilities reassign product expiration dates based on documented stability program data, the facility shall relabel products with new expiration dates. Reference Standard 5.6.2A, Requirements for Labeling of Cellular Therapy Products, applies.

Guidance

Reassigned expiration dates must be based primarily on the facility’s stability program. Scientific literature may also be used to supplement the stability program but should not replace the facility’s stability data. (SS)

☑ Actionable Checklist

• Develop and maintain a documented stability program to support reassignment of product expiration dates.
  • Include scientific literature as supplemental data, ensuring it does not replace facility data.
• Establish an SOP for relabeling products with new expiration dates based on stability data.
• Train staff on the SOP for relabeling and document training records.
• Implement a log to track all products with reassigned expiration dates and their stability data.
• Conduct regular audits to ensure compliance with the relabeling SOP and stability program.
• Review and update the stability program and relabeling SOP annually or as needed.

5.19 Discard and Disposal

[F]

The facility shall have policies, processes, and procedures regarding discard and disposal of products and aliquots, that are consistent with requirements outlined in the facility’s informed consent process and applicable laws and regulations. Standard 4.1 applies.

☑ Actionable Checklist

• Develop and maintain an SOP for the discard and disposal of cellular therapy products and aliquots.
  • Ensure the SOP aligns with the facility’s informed consent process.
  • Include references to applicable laws and regulations in the SOP.
• Train staff on the discard and disposal SOP and document training records.
• Conduct regular audits to verify compliance with discard and disposal procedures.
• Implement a log for tracking discarded and disposed products, including reasons and methods.
• Review and update the discard and disposal SOP annually or as regulations change.
• Include discard and disposal processes in the facility’s Validation Master Plan (VMP).

5.20 Evaluation to Make a Product Available for Distribution

The facility shall define requirements for inspections and test results necessary to make a product available for distribution. The facility shall ensure that these requirements are met before distribution. Standards 5.22.1, 5.26.2, 7.1.3, and 7.2.6.2 apply.

☑ Actionable Checklist

• Develop and document SOPs outlining inspection and testing requirements prior to product distribution.
  • Include specific criteria for acceptance and rejection in the SOPs.
• Implement a checklist or form to verify completion of all required inspections and tests.
• Ensure all test results are reviewed and approved by authorized personnel before product release.
• Maintain a log of all products evaluated for distribution, including inspection and test outcomes.
• Conduct regular audits of the evaluation process to ensure compliance with defined requirements.
• Train staff on the SOPs and evaluation process, documenting all training sessions and competency assessments.

5.20.1

Products shall not be made available for distribution or listed on a registry until the medical director or designee and the quality representative or designee have approved the release of the product.

Guidance

For facilities that have applied for a Biologics License Application (BLA) for cord blood products under the US FDA, regulations stipulate that the release of the product is solely in the hands of the quality unit. This decision must be free from influence from clinical, economic, and performance pressures. The organizational chart must reflect this independence. The quality unit must have the ability to assess and approve only those products that have met the parameters for safety, purity, and potency as defined by the program. (SS)

☑ Actionable Checklist

• Ensure the medical director or designee and the quality representative or designee are documented as authorized personnel for product release.
  • Update the organizational chart to reflect the independence of the quality unit.
• Develop and maintain an SOP outlining the approval process for product release, including roles and responsibilities.
• Implement a checklist or form for documenting the approval of each product by the medical director and quality representative.
• Conduct regular internal audits to verify compliance with the approval process and document findings.
• Train staff on the SOP for product release and maintain records of training and competency evaluations.
• Review and update the Validation Master Plan (VMP) to ensure it includes criteria for product safety, purity, and potency.

5.20.2

[F]

Before a product is made available for distribution, the records relevant to Standards 5.20.2.1 and 5.20.2.2 shall be reviewed. The responsibility for completion and review of these records shall be defined in an agreement between the applicable parties. Standard 4.2.3.2 applies.

Guidance

Agreements between the facility distributing a product and the facility receiving the product should
define who is responsible for completion and review of records related to procurement and processing, before that distribution step occurs. (SS)

☑ Actionable Checklist

• Define roles and responsibilities for record completion and review in an agreement with all applicable parties.
  • Ensure the agreement includes responsibilities for both the distributing and receiving facilities.
• Develop and maintain SOPs for the review of records relevant to Standards 5.20.2.1 and 5.20.2.2.
• Implement a checklist or form for documenting the review of records before product distribution.
• Conduct training sessions for staff on the procedures for record review and responsibilities as per the agreement.
• Perform regular audits to verify compliance with record review procedures and agreements.
• Document any deviations from the record review process and initiate CAPAs as necessary.

5.20.2.1 Donation Criteria

Review of donation criteria shall confirm that:

1. Donor informed consent was obtained.
2. Donor eligibility determination was performed, when applicable. Standards 5.10 and 7.2 apply.
3. The donor met other applicable selection criteria.
4. The procurement order was obtained.

Guidance

This standard details items that should be reviewed before distribution of any type of cell therapy product. However, in the case of cord blood, item #4 that requires obtaining a procurement order would usually not be applicable, especially in the private cord blood banking setting. However, a cord blood product that is collected with an intended recipient (ie, related sibling or parent) in mind would most likely be accompanied by a procurement order. (SS)

☑ Actionable Checklist

• Verify that donor informed consent forms are completed and filed in accordance with SOP CT-IC-01.
• Ensure donor eligibility determination is documented and aligns with SOP CT-ED-02.
  • Cross-reference donor eligibility with Standards 5.10 and 7.2 compliance checklist.
• Confirm that donor selection criteria are met and documented per SOP CT-DS-03.
• Obtain and document procurement order for applicable donations, referencing SOP CT-PO-04.
• Review and update all related SOPs annually or as needed to ensure compliance with current standards.
• Conduct periodic audits to verify compliance with donation criteria and document findings in the audit log.

5.20.2.2 Product Processing Review

Review of the final cellular therapy product processing record shall confirm that:

1. Processing order was obtained, if applicable.
2. Facility-defined specified requirements were achieved.
3. Records of processing, cryopreservation, and storage are complete and contain appropriate initials and/or signatures, and critical calculations have been verified.
4. Appropriate, in-date, critical reagents and materials were used and lot numbers recorded in a manner that ensures traceability.
5. Appropriate equipment was used and identification numbers recorded in a manner that ensures traceability.
6. The accuracy and completeness of the product labeling was verified.
7. All pending infectious disease testing, if applicable, was completed.

☑ Actionable Checklist

• Verify that a processing order was obtained and documented in the product processing record.
• Confirm that all facility-defined specified requirements for processing were met and documented.
• Ensure processing, cryopreservation, and storage records are complete with initials/signatures and verified critical calculations.
• Check that all critical reagents and materials used were in-date, and lot numbers are recorded for traceability.
• Confirm that all equipment used is appropriate, and identification numbers are recorded for traceability.
• Verify the accuracy and completeness of product labeling against SOP CT-Label-01.
• Ensure all pending infectious disease testing is completed and results are documented in the processing record.

5.20.2.3 Product Record Review

[Cord blood applicable]

Before final distribution, the following items shall be reviewed:

1. List of the specified requirements.
2. Acceptable values or range for each test.
3. Actual product value for each test.
4. Indication of whether each given value falls within the acceptable range.
5. Documentation that the product review was acceptable, and the identity of the person making that determination.
6. Comments or annotations if the product does not meet specified requirements.

☑ Actionable Checklist

• Develop and maintain an SOP for product record review before final distribution.
  • Include a checklist of specified requirements for each product.
  • Define acceptable values or ranges for each test.
• Implement a form or electronic system to capture actual product values for each test.
• Create a log to document whether each product value falls within the acceptable range.
• Ensure documentation includes the identity of the person who determined the product review was acceptable.
• Establish a procedure for adding comments or annotations if the product does not meet specified requirements.
• Conduct regular training sessions for staff on the product record review process and document attendance and competency.

5.20.3 Failure to Meet Specified Requirements

Products that do not meet specified requirements are considered nonconforming and shall not be used except as defined in Standard 7.2.6.2.

☑ Actionable Checklist

• Develop and implement an SOP for identifying and managing nonconforming products.
  • Include criteria for determining nonconformance.
  • Outline steps for segregation and labeling of nonconforming products.
• Train staff on the SOP for handling nonconforming products.
  • Document training completion and maintain records.
• Establish a log for recording instances of nonconforming products.
  • Include details such as product ID, nature of nonconformance, and disposition.
• Conduct regular audits to ensure compliance with nonconformance handling procedures.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.
• Implement a CAPA process for addressing root causes of nonconformance.

5.21 Distribution

[Cord blood applicable]

Upon request for distribution, the following items shall be reviewed:

1. Documentation that the product was requested. Standards 4.2.3.1 and 4.2.5 apply.
2. The accuracy and completeness of the product labeling and identification verified by two individuals or one individual and an electronic device that has been validated to fulfill the labeling identification function(s).
3. Product condition by visual inspection, including container closure and integrity.
4. Recipient identification, if applicable.
5. Documentation of compatibility for the intended recipient.

Guidance

#3 - The committee added the clause, “…including container closure and integrity…” for completeness. (SC)

☑ Actionable Checklist

• Verify and document the request for product distribution per SOP 4.2.3.1 and 4.2.5.
  • Ensure all request documentation is complete and filed in the distribution log.
• Confirm the accuracy and completeness of product labeling and identification.
  • Conduct verification by two individuals or one individual with a validated electronic device.
  • Record verification details in the labeling verification log.
• Perform a visual inspection of the product condition.
  • Check container closure and integrity, documenting findings in the inspection log.
• Verify recipient identification, if applicable, and document in the recipient verification form.
• Ensure documentation of compatibility for the intended recipient is complete and filed.

5.21.1

Instructions shall be made available for the handling, storage, and preparation of products
for administration. Standard 4.3.5 applies.

Guidance

Facilities that distribute cellular therapy products should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product. Such facilities should also maintain a chain of identity that ensures permanent and transparent association of a cell or gene therapy’s unique identifiers from procurement of tissue or cells throughout the full product(s) lifecycle, including posttreatment monitoring of the recipient. (SS)

☑ Actionable Checklist

• Develop and maintain SOPs for handling, storage, and preparation of products for administration.
  • Ensure SOPs include detailed instructions for each step of the process.
  • Review and update SOPs annually or as needed.
• Implement a chain of custody log to document the guardianship of each cellular therapy product.
  • Ensure the log is concurrent, permanent, and auditable.
• Establish a chain of identity system to track unique identifiers from procurement to posttreatment.
  • Ensure system allows for transparent association of identifiers throughout the product lifecycle.
• Conduct regular training sessions for staff on handling, storage, and preparation procedures.
  • Document all training sessions and maintain records.
• Perform internal audits to verify compliance with SOPs and documentation requirements.
  • Address any identified gaps through CAPAs.

5.22 Product Issue

[F]

Before issue, the following items shall be reviewed:

1. Medical order for issuing the product.
2. The accuracy and completeness of the product labeling and identification verified by two individuals or electronic equivalent.
3. Product condition by visual inspection, including container closure and integrity.
4. Recipient identification.
5. Documentation of compatibility for the intended recipient:
   a) ABO and other blood group and type antigen compatibility, if applicable.
   b) HLA compatibility, if applicable.

Guidance

#3 - The committee added the clause, “…including container closure and integrity…” for completeness. (SC)

☑ Actionable Checklist

• Review and verify the medical order for issuing the product.
• Confirm accuracy and completeness of product labeling and identification with two individuals or electronic equivalent.
  • Document verification in the product issue log.
• Conduct visual inspection of product condition, including container closure and integrity.
  • Record findings in the inspection checklist.
• Verify recipient identification against the medical order.
  • Ensure documentation is complete in the recipient verification form.
• Document compatibility for the intended recipient.
  • Verify ABO and other blood group and type antigen compatibility, if applicable.
  • Confirm HLA compatibility, if applicable, and document in the compatibility log.

5.22.1

[F]

The issuing facility shall review and verify the following items at the time of final cellular therapy product distribution/issue:

1. Recipient’s name and unique identifier(s).
2. Donation identification number.
3. Product description code, type of collection, and division code.
4. Product name and attributes.
5. Unique donor identifier, if available.
6. Product condition by visual inspection, including container closure and integrity.
7. Names and/or identifiers of persons verifying that the product is the product intended for the recipient.
8. Identification of the person issuing the product.
9. Identification of the person to whom the product was issued.
10. Date(s) and time(s) issue.

Guidance

Facilities that issue cellular therapy products by apheresis should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product. Such facilities should also maintain a chain of identity that ensures permanent and transparent association of a cell or gene therapy’s unique identifiers from procurement of tissue or cells throughout the full product(s) lifecycle, including posttreatment monitoring of the recipient.

All facilities or organizations involved in manufacturing or distribution must ensure the identity of the final product and its contents. The identification of the intended recipient, when known, is a critical element of product identity when it is manufactured solely for that intended recipient. (SS)

#6 - The committee added the clause, “…including container closure and integrity…” to subnumber 6 for completeness. (SC)

#10 - The committee edited subnumber 10 for clarity, replacing “Date and time of issue” with “Date(s) and time(s) of issue.” (SC)

☑ Actionable Checklist

• Review and verify the recipient’s name and unique identifier(s) against the order and product label.
• Confirm the donation identification number matches the documentation and product label.
• Check the product description code, type of collection, and division code for accuracy.
• Verify the product name and attributes are correctly documented and labeled.
• Ensure the unique donor identifier, if available, is correctly associated with the product.
• Conduct a visual inspection of the product condition, including container closure and integrity.
• Record the names and/or identifiers of persons verifying the product is intended for the recipient.
• Document the identification of the person issuing the product.
• Record the identification of the person to whom the product was issued.
• Log the date(s) and time(s) of issue in the product distribution records.

5.22.2

At distribution and issue of allogeneic products, the following information shall accompany the product or be readily available wherever the product is located to maintain the chain of custody:

1. A statement that the donor has been determined to be eligible or ineligible, or donor eligibility determination is incomplete, noting the name and address of the facility that made the donor eligibility determination. Standard 5.10.5 applies.
2. A statement that the infectious disease testing was performed by a laboratory that has been certified to perform such testing on human samples under current CLIA regulations or that has met equivalent requirements as determined by the CMS. For testing facilities located outside of the United States, the use of a non-US laboratory as a testing center is permissible if authorized by the FDA or relevant Competent Authority as an approved laboratory for infectious disease testing in that country.
3. A listing and interpretation of the results of all donor screening and infectious disease tests performed or pending.
4. For a product from an ineligible donor, a statement noting the reason(s) for the determination of ineligibility.
5. Instructions for the storage and handling of the products before administration.
6. A statement that the product was stored under the applicable environmental conditions as outlined in the instructions. Standard 7.2.6.2 applies.

Guidance

#6 - The committee added subnumber 6 to the edition for completeness. This closes the circle of what needs to be included for the distribution of allogeneic products. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for documenting donor eligibility status, including the name and address of the facility that made the determination.
  • Ensure SOP includes procedures for handling incomplete donor eligibility determinations.
• Verify that infectious disease testing is conducted by a CLIA-certified laboratory or equivalent, and document this certification.
  • Maintain a list of approved non-US laboratories authorized by the FDA or relevant Competent Authority.
• Create a form or log to list and interpret results of all donor screening and infectious disease tests, including pending results.
• Develop a procedure for documenting reasons for donor ineligibility and ensure it accompanies the product.
• Establish clear instructions for the storage and handling of products before administration, and include these with the product.
• Implement a system to verify and document that products have been stored under the specified environmental conditions as per the instructions.

5.22.3

Records provided at the time of distribution for donors with incomplete eligibility determination shall indicate the testing and screening that was completed and the testing and screening that has not yet been completed.

☑ Actionable Checklist

• Develop and implement an SOP for documenting donor eligibility determination status.
  • Include steps for recording completed and incomplete testing and screening.
• Create a standardized form or log to accompany distributed products, detailing donor eligibility status.
• Train staff on the SOP and use of the form/log for recording eligibility determination.
• Conduct regular audits to ensure compliance with documentation requirements for distributed products.
• Review and update the SOP and form/log annually or as needed to reflect any changes in regulations or practices.
• Maintain records of all distributed products with incomplete donor eligibility determination for traceability.

5.22.4 Return of Cellular Therapy Products

[F]

The facility shall have a policy for the return of cellular therapy products that includes:

1. The reason for the return of the cellular therapy product.
2. Inspection of the product for the following elements that can affect product quality, including, but not limited to:
   a) Maintenance of appropriate storage and transportation conditions.
   b) Integrity of the product container closure.
   c) Traceability and chain of custody of the cellular therapy product.
   d) Product expiration date and time.
3. Determination of the acceptability and disposition of the product, such as reissue, storage, further manufacturing, or discard.
4. Notification and consultation with the patient’s physician or other relevant parties, as applicable.

Guidance

This standard requires that facilities establish and maintain policies for managing returned cellular therapy products to protect product integrity and ensure recipient safety. The following guidance addresses each requirement systematically, integrating with existing processes such as product release (Standard 5.20), nonconforming products (Standard 7.2), and labeling controls (Standard 5.6).

#1, The reason for the return of the cellular therapy product.
The facility’s policy must require that the reason for the return be clearly documented and linked to the product’s unique identifier, as mandated by Standard 5.5 (Product Identification and Traceability). Examples of reasons for return include, but are not limited to:

• Adverse reaction during infusion: An allergic response to cryoprotectant (eg, DMSO sensitivity), prompting return for investigation or reprocessing (see Reich-Slotky et al, 2022).
• Expiration of a thawed product: Exceeding a 24-hour stability limit due to delays in administration (eg, patient rescheduling) (see Reich-Slotky et al, 2022).
• Transportation issues: A temperature excursion above –150 C for cryopreserved products due to shipping equipment failure (Standard 5.17.2.2).
• Cancellation of a scheduled transplantation: Deterioration of the patient’s condition (eg, infection), canceling the procedure (Cullis, 2016).
• Product misidentification: Detection of a wrong patient label at the clinical site, necessitating return for safety (Standard 5.6).

Returns represent deviations from standard procedures and must be managed through the facility’s deviation management system per Chapter 7, Deviations, Nonconformances, and Adverse Events. Thisensures traceability and accountability, aligning with FDA good tissue practice requirements (21 CFR 1271), which emphasize documenting deviations.

#2, Inspection of the product for elements that can affect product quality.
The facility must define procedures for inspecting returned products upon receipt, focusing on elements that impact quality. These inspections provide objective evidence for disposition decisions and must be documented in detail.

#2(a), Maintenance of appropriate storage and transportation conditions.
Inspection procedures should verify compliance with validated storage and transportation conditions.
For example:

• Cryopreserved products: Per Standard 5.17.2.2, these must be maintained at or below –150 C. Review continuous temperature monitoring data (Standard 5.7.3.1) from data loggers to confirm no excursions occurred.
• Thawed products: Check stability parameters (eg, time at 2-8 C or room temperature) against facility limits derived from stability studies (Standard 5.18; Reich-Slotky et al, 2022). Note that thawed HPCs remain viable for 24 to 72 hours, depending on conditions.

The FDA Guidance for Industry on HCT/Ps (August 2007) recommends documenting environmental conditions during handling. The duration outside controlled environments must be recorded to assess compliance.

#2(b), Integrity of the product container closure.
Container closure integrity must be assessed via visual inspection for cracks, leaks, or seal breaches (Standard 5.8). For cryopreserved products, integrity prevents liquid nitrogen ingress, which could compromise viability (Cullis, 2016). Facility procedures may include additional tests such as dye ingress or microbial sterility checks if contamination is suspected. Findings (eg, photographs, checklists) must be documented.

#2(c), Traceability and chain of custody of the cellular therapy product.
Verification of chain of identity (COI) and chain of custody (COC) is required per Standard 5.5.1:

• Confirm product identifiers [eg, ISBT 128 label (Standard 5.6.1)] match procurement and processing records.
• Review transport documentation (eg, shipping logs, courier receipts) to ensure unbroken custody (21 CFR 1271.265).

A dual-check system (two staff or one with electronic validation) is a suggestion to minimize mix-up risks, enhancing traceability.

#2(d), Product expiration date and time.
The expiration date and time must be verified against the validated expiry (Standard 5.18.1). For cryopreserved products, stability studies support this date, while thawed products have shorter windows (eg, 24 hours). Documentation must confirm whether the product remains within its usable period upon return.

#3, Determination of the acceptability and disposition of the product.
The facility must define criteria for determining acceptability and disposition (reissue, storage, further manufacturing, or discard). Decisions must involve the laboratory director, laboratory medical director, and quality representative, with roles specified per Standard 5.20.1. Considerations include:

• Product integrity: Evidence of maintained storage conditions and container integrity from inspection.
• Expiration: Confirmation the product is within its validated expiry.
• Clinical need: For nonconforming products, urgent medical need documentation per Standard 7.2.6.2.

Products exceeding stability limits could be discarded unless reprocessing (eg, washing out cryoprotectant) is validated. Examples:

• Reissue: A cryopreserved HPC returned due to a canceled transplantation, with intact container and temperature logs, could be reissued after physician approval.
• Discard: A thawed product returned after 48 hours at room temperature (exceeding 24-hour stability) would be discarded as nonconforming.

#4, Notification and consultation with the patient’s physician or other relevant parties.
Facility policies must outline communication protocols:

• Recipient’s physician: Notify promptly of the return and consult on disposition (Standard 5.21.1) to assess clinical impact, aligning with 21 CFR 1271.65 for urgent-use scenarios.
• Processing/procurement facilities: Notify if the return affects quality or safety (eg, contamination), per Standard 7.3.2.
• Regulatory authorities: Report significant nonconformances affecting distributed products to the FDA [eg, via Form FDA 3486 (21 CFR 1271.350)].

All consultations, decisions, and authorizations (including dates, times, and signatures) must be documented for audit readiness.

Applicable standards:

• 5.20: Evaluation to Make a Product Available for Distribution (release criteria).
• 7.0: Deviations, Nonconformances, and Adverse Events (management of exceptions).
• 5.6: Labels, Labeling, and Labeling Controls (traceability and COI maintenance).

References

1. Code of federal regulations. Title 21 CFR Part 1271: Human cells, tissues, and cellular and tissue based products (HCT/Ps). US Government Publishing Office, 2024 (updated annually). [Available here]
   -Cited for good tissue practice requirements, traceability (21 CFR 1271.265), urgent use (21 CFR 1271.65), reporting (21 CFR  1271.350), and record retention (21 CFR 1271.55).
    
2. Food and Drug Administration. Guidance for industry: Eligibility determination for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps) (August 2007). Silver Spring, MD: CBER Office of Communication, Outreach, and Development, 2007. [Available here]
   -Cited for documenting environmental conditions during handling.
    
3. Reich-Slotky R, Vasovic LV, Land KJ, et al. Cryopreserved hematopoietic stem/progenitor cells stability program development, current status and recommendations: A brief report from the AABB-ISCT Joint Working Group Cellular Therapy Product Stability Project team. Transfusion 2022;62: 651-62.
   -Cited for stability of thawed hematopoietic stem cell products (24-72 hours).
    
4. Cullis HM. Cryopreservation containers for cellular therapy products. In: Areman EM, Loper K, eds. Cellular therapy: Principles, methods, and regulations. 2nd ed. Bethesda, MD: AABB, 2016.
   -Cited for importance of container integrity in cryopreserved products. (SS)

​The committee added new standard 5.22.4 to the edition for completeness. The standard was added to ensure that facilities that have products returned identify those products and follow the requirements in subnumbers 1 – 4 prior to any potential reissue. The committee felt that there was a gap by not having a requirement focused on the return of a cellular therapy product. (SC)

☑ Actionable Checklist

• Develop and implement a policy for the return of cellular therapy products.
  • Include documentation of the reason for return linked to the product’s unique identifier.
  • Ensure the policy aligns with Standard 5.5 for Product Identification and Traceability.
• Establish procedures for inspecting returned products.
  • Verify maintenance of appropriate storage and transportation conditions.
  • Check integrity of the product container closure.
  • Confirm traceability and chain of custody of the product.
  • Assess product expiration date and time.
• Define criteria for determining the acceptability and disposition of returned products.
  • Include options for reissue, storage, further manufacturing, or discard.
• Create a protocol for notifying and consulting with the patient’s physician or relevant parties.
• Integrate return management with existing processes for product release, nonconforming products, and labeling controls.
• Document all returns in the deviation management system, ensuring traceability and accountability.

5.22.5 Reissue of Cellular Therapy Products

[F]

The facility shall have a policy for the reissue of cellular therapy products that includes:

1. Criteria for reissue eligibility.
2. An approval process, including authorization from the laboratory director in consultation with the patient’s physician or other relevant parties, as applicable.
3. Maintenance of traceability and chain of custody.
4. Product preparation for reissue, including label verification.

Standard 5.22 applies.

Guidance

This standard requires facilities to establish and maintain a written policy for the reissue of cellular therapy products—such as HPCs, cord blood, or other cellular therapies—that have been previously distributed or issued and returned, or require reassignment to a new recipient or use. The intent is to ensure that reissued products remain safe, potent, and traceable, protecting recipient safety and maintaining compliance with these CT Standards. The policy must address each substandard explicitly, integrating requirements from related standards (eg, Standards 5.5, 5.6, 5.22) and applicable regulations (eg, 21 CFR 1271).

#1, Criteria for reissue eligibility.
The facility must define specific criteria to evaluate whether a product is eligible for reissue. These criteria ensure the product’s quality and safety are preserved after return. Eligibility requires verification that:

• Storage conditions (eg, at or below –150 C for cryopreserved cord blood per Standard 5.17.2.2) have been maintained, supported by continuous monitoring records or validated shipping container data (FDA, 2020).
• Container closure integrity is intact, confirmed by visual inspection for cracks, leaks, or tampering (Standard 5.22; Reich-Slotky et al, 2022).
• The product remains within its stability parameters (eg, expiration date, viable cell recovery, potency), validated by the facility’s stability program (Standard 5.18.3) or peer-reviewed data.
• No prior use, contamination, or unreported deviations have occurred since distribution (Standard 5.20).

For example, a returned HPC unit must have documented temperature logs, an intact cryobag, and viable cell counts within acceptable ranges to be considered for reissue.

#2, Approval process.
The policy must specify an approval process involving the laboratory director, who is responsible for technical oversight (Standard 1.1.4.2), in consultation with the patient’s physician or other relevant parties (eg, clinical program director per Standard 1.1.5.2). This ensures both technical and clinical suitability.

• The laboratory director reviews product quality data (eg, storage, integrity, stability) and authorizes reissue, documenting approval with a signature and date.
• Consultation with the physician confirms clinical appropriateness (eg, HLA or ABO compatibility per Standard 5.22), with outcomes recorded.
• When multiple facilities are involved, agreements (Standard 4.2.3) define communication and decision-making responsibilities.

An example is a returned cord blood unit requiring the laboratory director to verify stability and the physician to confirm patient need, with both approvals documented.

#3, Maintenance of traceability and chain of custody.
The facility must maintain chain of identity (COI) and chain of custody (COC) throughout the reissue process, as defined in Standards 5.5 and 5.22:

• COI ensures the product’s unique identifier (eg, ISBT 128 donation identification number per Standard 5.4.1) links it to the donor and recipient across all stages—procurement, processing, distribution, return, and reissue (ICCBBA, 2023). Records must enable bidirectional traceability, such as through a cross-reference log if a new identifier is assigned.
• COC tracks physical possession, documenting who handled the product, when, and under what conditions (eg, transport logs, return records) (FDA, 2020).

For instance, a returned HPC unit’s records must show its full journey, with COC maintained (Standard 5.7) and COI preserved via consistent labeling.

#4, Product preparation for reissue, including label verification.
Preparation for reissue must ensure the product meets distribution standards (Standard 5.21), with label verification confirming accuracy and compliance (Standard 5.6):

• The product is prepared (eg, repackaged in a qualified shipping container per Standard 5.7.2) to maintain required conditions, following facility or manufacturer protocols.
• Label verification, performed by two individuals or one individual with a validated electronic device (eg, barcode scanner), confirms:
  – Product identifiers match records (Standard 5.5.1).
  – Labels include all required elements (Reference Standard 5.6.2A; eg, product name, expiration date, biohazard warnings if applicable).
  – Container integrity is intact, ensuring label readability and product safety (Reich-Slotky et al, 2022).
• Updated accompanying documentation (eg, stability results, return history) must be provided (Standard 5.22.2).

For example, a cryopreserved product requires temperature log review, label confirmation, and attachment of reissue approvals before shipment.

Additional notes:

• Records of reissued products must include original distribution details, return documentation, reissue evaluation results, authorization signatures, label verification evidence, and notifications to the recipient and physician, retained for at least 10 years (Standard 6.2.9).
• Compliance with FDA regulations (eg, 21 CFR 1271) is required, particularly for interstate transport or international reissue (FDA, 2020).
• Examples of objective evidence include temperature logs, inspection reports, approval forms, traceability records, and verified labels.

References

1. Food and Drug Administration. Guidance for industry and Food and Drug Administration staff: Regulatory considerations for human cells, tissues, and cellular and tissue-based products: Minimal manipulation and homologous use. Silver Spring, MD: CBER Office of Communication, Outreach, and Development, 2020.
2. ST-001 ISBT 128 standard technical specification. Redlands, CA: ICCBBA, 2023. Available here.
3. Reich-Slotky R, Vasovic LV, Land KJ, et al. Cryopreserved hematopoietic stem/progenitor cells stability program development, current status and recommendations: A brief report from the AABB-ISCT Joint Working Group Cellular Therapy Product Stability Project team. Transfusion 2022;62: 651-62. (SS)

​The committee added new standard 5.22.5 to the edition to ensure that facilities that are reissuing returned products to inventory have to follow the 4 subnumbers to ensure that the safest possible product is reissued. (SC)

Clinical Activities

☑ Actionable Checklist

• Develop and document a policy for the reissue of cellular therapy products, incorporating criteria for eligibility, approval process, traceability, and preparation.
  • Define specific criteria for reissue eligibility, including storage conditions, container integrity, stability parameters, and absence of contamination.
  • Establish an approval process requiring authorization from the laboratory director in consultation with the patient’s physician.
  • Ensure traceability and chain of custody are maintained throughout the reissue process.
  • Outline procedures for product preparation, including label verification before reissue.
• Create and maintain SOPs related to the reissue process, referencing relevant standards and regulations.
• Implement a system for documenting and reviewing all reissue activities, including eligibility assessments and approvals.
• Conduct regular training sessions for staff on the reissue policy and procedures, documenting attendance and competency evaluations.
• Perform internal audits to verify compliance with the reissue policy and identify areas for improvement.
• Review and update the reissue policy and related SOPs annually or as needed based on audit findings or regulatory changes.

5.23 Clinical Program

The facility shall have policies, processes, and procedures for patient care, including the administration of specific therapies and medical interventions while maintaining the chain of identity and chain of custody.

Guidance

These standards are applicable to facilities seeking accreditation for clinical activities. If a facility contracts out any part of the process (collection through administration), conformance to the CT Standards should be defined in agreements. Throughout the CT Standards, the term “patient” is used to refer to the individual potentially receiving cellular therapy products and related treatment. The term “patient” has been chosen over “recipient” because, in some cases, these individuals may not actually end up receiving a product. (SS)

The committee added the clause, “…and chain of custody” for completeness. (SC)

☑ Actionable Checklist

• Develop and maintain SOPs for patient care specific to cellular therapy, including administration protocols.
  • Include procedures for maintaining chain of identity and chain of custody.
• Ensure all staff involved in patient care are trained on SOPs and maintain up-to-date training records.
• Conduct regular audits to verify adherence to patient care SOPs and document findings.
• Establish agreements with contracted facilities outlining compliance with CT Standards for any outsourced processes.
• Implement a tracking system to monitor chain of identity and chain of custody for all cellular therapy products.
• Review and update policies and procedures annually or as needed based on audit results and regulatory changes.

5.23.1 Patient (Recipient) Evaluation

The facility shall define clinical indications and ensure that evaluation criteria are met and continue to be met before treatment. This evaluation shall be conducted by a health-care professional and approved by a physician.

Guidance

This standard refers to the responsibilities of the clinical facility. It is not expected that the processing facility should verify such an evaluation has been performed for each patient before transporting the product to the clinical facility. However, an agreement should be in place between the processing and clinical facilities specifying that the clinical facility will have 1) performed the appropriate evaluation of the recipient before a product is transported and 2) provided orders and defined responsibility for patient care. (SS)

☑ Actionable Checklist

• Define and document clinical indications for cellular therapy treatments in an SOP.
• Establish criteria for patient evaluations to be conducted by a healthcare professional.
• Ensure physician approval is documented for each patient evaluation prior to treatment.
• Develop and maintain an agreement with the clinical facility specifying evaluation responsibilities.
  • Include clauses for pre-transport evaluation verification and patient care responsibility.
• Conduct regular audits of patient evaluation records to ensure compliance with defined criteria.
• Review and update the patient evaluation SOP annually or as needed based on regulatory changes.

5.23.2

The facility shall ensure that orders and responsibility for the provision of patient care are defined and communicated, including whenever responsibility changes.

Guidance

The committee added the clause “including” in the standard to expand the scope of the communication requirements beyond just when responsibility changes for patient care. (SC)

☑ Actionable Checklist

• Define and document roles and responsibilities for patient care in an SOP.
  • Include procedures for communication when responsibilities change.
• Implement a communication protocol for changes in patient care responsibility.
  • Use a standardized form or log to document changes.
• Train staff on the SOP and communication protocol.
  • Maintain training records and competency evaluations.
• Conduct regular audits to ensure compliance with the communication protocol.
  • Document findings and corrective actions if needed.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.

5.24 Clinical Care of the Recipient

[F]

The facility shall address the clinical care of the recipient, including the following, if applicable:

1. Blood products.
2. Chemotherapy.
3. Radiation therapy.
4. Conditioning regimens.
5. Infectious disease management.
6. Graft-vs-host disease, cytokine release syndrome, and other cellular-therapy-associated complications.

Standard 2.2 applies.

☑ Actionable Checklist

• Develop and maintain SOPs for the administration of blood products to recipients.
  • Include criteria for transfusion and monitoring protocols.
• Establish protocols for chemotherapy administration, including dosing and schedule.
  • Document pre- and post-treatment assessments.
• Create radiation therapy guidelines, detailing treatment planning and safety measures.
  • Ensure coordination with radiation oncology services.
• Define conditioning regimens with specific protocols for each therapy type.
  • Include patient monitoring and response evaluation.
• Implement infectious disease management protocols, including screening and prophylaxis.
  • Maintain a log of infection control measures and outcomes.
• Develop management plans for graft-vs-host disease and cytokine release syndrome.
  • Include emergency response procedures and treatment algorithms.

5.24.1 Medical Orders

Orders for clinical care of the recipient shall uniquely identify the recipient and medical treatment ordered. Specific instructions shall be provided in the order.

☑ Actionable Checklist

• Ensure all medical orders include a unique identifier for each recipient.
  • Verify that the unique identifier is consistent across all related documentation.
• Include specific instructions for medical treatment in each order.
  • Review orders for completeness and clarity before implementation.
• Maintain a log of all medical orders, including recipient identifiers and treatment details.
• Conduct regular audits of medical orders to ensure compliance with identification and instruction requirements.
• Update SOPs to reflect the process for verifying and documenting medical orders.
• Train staff on the importance of unique identification and specific instructions in medical orders.

5.24.1.1

Medical therapy(ies) shall be ordered by a qualified physician or an authorized healthcare professional.

☑ Actionable Checklist

• Verify that all medical therapy orders are documented in the patient’s medical record.
  • Ensure orders include the name of the qualified physician or authorized healthcare professional.
• Maintain a current list of qualified physicians and authorized healthcare professionals.
• Implement an SOP for verifying the credentials of individuals authorized to order medical therapies.
• Conduct regular audits to ensure compliance with the SOP for medical therapy orders.
• Document all audits and corrective actions taken in response to non-compliance.

5.24.1.2

[F]

Orders for cellular therapy product administration shall uniquely identify the recipient, type of cellular therapy product ordered, and the dose. The order shall be obtained before the product is released for administration. Specific instructions for administration shall be provided.

Guidance

This standard refers to the responsibilities of the clinical facility. However, there should be an agreement between the clinical and manufacturing facilities that outlines the responsibilities and timing for clinical care and orders for cellular therapy administration. (SS)

☑ Actionable Checklist

• Develop and implement an SOP for verifying orders for cellular therapy product administration.
  • Ensure the SOP includes steps for unique identification of the recipient, product type, and dose.
  • Include procedures for obtaining the order before product release.
• Create a standardized order form that captures recipient identification, product type, dose, and administration instructions.
• Establish a documented agreement between clinical and manufacturing facilities outlining responsibilities and timing for order processing.
• Train staff on the SOP and use of the order form, documenting all training sessions.
• Conduct regular audits to ensure compliance with order verification and documentation procedures.
• Maintain a log of all orders received, including verification of recipient identity, product type, and dose, with signatures and dates.

5.25 Preparation of the Recipient for Administration of Cellular Therapy Products

[F]

The facility shall have policies, processes, and procedures for the preparation of the recipient for administration of cellular therapy product(s), which shall address, at a minimum, the following:

1. Administration of the preparative regimen, if applicable.
2. Prevention of cellular therapy product-associated toxicities.
3. Management of cellular therapy product-associated toxicities.

Standard 5.26.1 applies.

☑ Actionable Checklist

• Develop and maintain SOPs for administering the preparative regimen, including dosing schedules and monitoring requirements.
  • Ensure SOPs are reviewed and approved by qualified personnel.
• Implement procedures to identify and mitigate potential cellular therapy product-associated toxicities.
  • Include risk assessment and preventive measures in SOPs.
• Establish protocols for the management of cellular therapy product-associated toxicities.
  • Document emergency response procedures and staff training.
• Conduct regular training sessions for staff on the preparation and administration processes.
  • Maintain up-to-date training records and competency evaluations.
• Perform internal audits to verify compliance with preparation and administration procedures.
  • Document findings and implement corrective actions as needed.
• Review and update policies and procedures annually or as new information becomes available.

5.26 Receipt and Storage of the Product

☑ Actionable Checklist

• Develop and implement an SOP for the receipt and storage of cellular therapy products.
  • Include procedures for verifying product identity and integrity upon receipt.
  • Define storage conditions and monitoring requirements for each product type.
• Train staff on the SOP for receipt and storage, documenting all training sessions.
• Maintain a log for recording receipt details, including date, time, condition, and identity verification.
• Implement a system for continuous monitoring of storage conditions, with alarms for deviations.
• Conduct regular audits of storage areas to ensure compliance with defined conditions.
• Document and review any deviations from the SOP, initiating CAPAs as necessary.

5.26.1 Receipt of Cellular Therapy Products

The clinical facility shall have procedures for the receipt and preparation of products while maintaining the chain of identity and chain of custody. Standards 5.5, 5.6, 5.8, and 5.20 apply.

☑ Actionable Checklist

• Develop and implement SOPs for the receipt and preparation of cellular therapy products, ensuring chain of identity and custody.
  • Include procedures for verifying product identification upon receipt.
  • Outline steps for documenting receipt in the product log.
• Train staff on SOPs related to product receipt and preparation, ensuring understanding of chain of identity and custody.
  • Maintain training records and competency evaluations for all relevant staff.
• Conduct regular internal audits to verify compliance with receipt and preparation procedures.
  • Document findings and implement corrective actions as needed.
• Maintain a log for all received products, including date, time, and condition upon receipt.
• Review and update SOPs annually or as needed to reflect changes in standards or processes.
• Implement a system for tracking deviations and CAPAs related to product receipt and preparation.

5.26.2

[F]

The clinical facility shall review and verify the following items at the time of final cellular therapy product receipt:

1. Recipient’s name and unique identifier(s).
2. Donation identification number.
3. Product description code, type of collection, and division code.
4. Product name and attributes.
5. Product condition by visual inspection, including container closure and integrity. Standard 4.1 applies.
6. Summary of donor eligibility determination. Standards 5.22.2 and 5.22.3 apply.

Guidance

The committee added the clause, “…including container closure and integrity…” for completeness. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for verifying recipient’s name and unique identifier(s) at product receipt.
• Create a form or log to document the verification of the donation identification number.
• Ensure the product description code, type of collection, and division code are checked and recorded upon receipt.
• Verify and document the product name and attributes using a standardized checklist.
• Perform and record a visual inspection of the product condition, including container closure and integrity.
  • Reference Standard 4.1 in the inspection SOP.
• Review and document the summary of donor eligibility determination, ensuring compliance with Standards 5.22.2 and 5.22.3.

5.26.3 Storage at Administering Facility

The administering facility shall maintain the product according to specifications provided by the processing facility.

☑ Actionable Checklist

• Verify that the administering facility has received and documented the storage specifications from the processing facility.
  • Ensure the specifications include temperature, humidity, and any other relevant storage conditions.
• Develop and implement an SOP for maintaining storage conditions as per the provided specifications.
• Conduct and document regular checks to ensure storage conditions meet the specified requirements.
  • Use calibrated equipment for monitoring temperature and other conditions.
• Train staff on the SOP for storage and document completion of training.
• Maintain a log of storage condition deviations and corrective actions taken.
• Include storage condition checks in regular internal audits and document findings.

5.27 Administration

[F]

Immediately before the administration of the final cellular therapy product, two individuals [or one individual and an electronic device that has been validated to fulfill the labeling identification function(s)] at the clinical facility shall confirm the identity of the product and the intended recipient. Intended recipients shall be identified using at least two identifiers.

☑ Actionable Checklist

• Develop and implement an SOP for product and recipient identity verification prior to administration.
  • Include procedures for using two identifiers for the intended recipient.
  • Specify roles of the two individuals or validated electronic device in the verification process.
• Validate any electronic devices used for labeling identification functions.
  • Document validation results and maintain records.
• Train clinical staff on the identity verification process.
  • Maintain training records and competency evaluations.
• Conduct regular audits to ensure compliance with the identity verification SOP.
  • Document audit findings and corrective actions if needed.
• Maintain a log of all product administrations, including identity verification details.
• Review and update the SOP annually or as needed based on audit findings or process changes.

5.27.1

The facility shall have policies, processes, and procedures for the administration of cellular therapy products. These shall be consistent with information contained in the current Circular of Information for the Use of Cellular Therapy Products, investigator’s brochure for investigational products, and/or package insert for licensed cellular therapy products.

☑ Actionable Checklist

• Develop and maintain SOPs for the administration of cellular therapy products referencing the Circular of Information.
  • Include procedures for verifying product information against the investigator’s brochure or package insert.
• Conduct a gap analysis to ensure all policies align with the Circular of Information and update as necessary.
• Implement a training program for staff on the administration procedures and document completion.
• Maintain a log of all administered cellular therapy products, including verification checks.
• Schedule regular reviews of the SOPs to incorporate updates from the Circular of Information or product inserts.
• Document any deviations from the SOPs and initiate CAPAs as needed.

5.27.2

The clinical facility shall have policies, processes, and procedures for monitoring and observation of the recipient commensurate with the nature of the procedure and product type. These shall include:

1. Infusional toxicities and adverse reactions resulting from cellular therapy product administration.
2. Prevention of regimen-related toxicities.
3. Management of regimen-related toxicities.
4. Identification and management of red cell antigen incompatibility.
5. Recipient immunosuppression for allogeneic cellular products.
6. Treatment of, or prophylaxis for, infectious disease.
7. Use of blood products.
8. Management of graft-vs-host-disease for allogeneic products.
9. Complications of immune effector cell therapy.

Guidance

Applicability of the items listed above will depend on the nature of the cell therapy product and procedures that the facility is performing. As these are critical issues, consideration of the items relevant to the cellular therapy product in question should be noted in policies, processes, and procedures. (SS)

☑ Actionable Checklist

• Develop and maintain SOPs for monitoring infusional toxicities and adverse reactions specific to each cellular therapy product.
• Implement procedures for the prevention and management of regimen-related toxicities, including training staff on these protocols.
• Establish a protocol for identifying and managing red cell antigen incompatibility, including documentation in patient records.
• Create a policy for recipient immunosuppression management for allogeneic cellular products, with regular review and updates.
• Ensure procedures are in place for the treatment and prophylaxis of infectious diseases, including maintaining an up-to-date infectious disease log.
• Document the use of blood products in cellular therapy, including indications and outcomes, in a dedicated log.
• Develop management plans for graft-vs-host disease in allogeneic products, ensuring staff are trained and competent in these procedures.
• Create protocols for managing complications of immune effector cell therapy, with a focus on early detection and intervention.

5.27.3

[F]

There shall be procedures for recording adverse events and processes for the communication of such events from the clinical facility to the issuing facility and/or registry while maintaining chain of identity. Standards 4.3.2 and 4.3.3 and Chapter 7, Deviations, Nonconformances, and Adverse Events, apply.

☑ Actionable Checklist

• Develop and implement an SOP for recording adverse events, ensuring it includes steps for documentation and communication.
  • Reference SOP in alignment with Standards 4.3.2 and 4.3.3.
• Establish a process for maintaining the chain of identity during adverse event reporting.
  • Use a standardized form or log to document chain of identity.
• Train staff on the procedures for adverse event recording and communication.
  • Maintain training records and competency evaluations.
• Set up a communication protocol between the clinical facility and the issuing facility/registry for adverse events.
  • Document communication in a communication log.
• Conduct regular audits to ensure compliance with the adverse event recording and communication procedures.
• Review and update the adverse event SOP and related documents annually or as needed.

5.27.3.1

Responsibility for treating recipient adverse events shall be defined. Standard 7.3.4 applies.

☑ Actionable Checklist

• Define and document roles and responsibilities for treating recipient adverse events in an SOP.
  • Include specific actions to be taken by each role during an adverse event.
• Ensure SOP for treating recipient adverse events is aligned with Standard 7.3.4.
• Conduct training sessions on the SOP for all relevant staff and document attendance.
• Maintain a log of all recipient adverse events, including actions taken and outcomes.
• Review and update the SOP annually or after any significant process changes.
• Include recipient adverse event management in regular internal audits to ensure compliance.

5.27.4 Records of Administration

[F]

Records of administration shall include:

1. Patient’s name and unique identifier(s).
2. Donation identification number.
3. Product description code, type of collection, and division code.
4. Product name and attributes.
5. Medical order for administration.
6. Confirmation of recipient and product identity before administration.
7. Names and/or identifiers of persons who administered the product.
8. Dates and times of product administration initiation and completion.
9. All administration information, including the patient’s vital signs and the time of all recorded events.
10. Whether any adverse events occurred, including a reference to the appropriate documentation of adverse event forms.
11. Records of notification if an adverse event occurred.
12. Critical steps related to product administration shall be entered into the permanent medical record by the ordering or administering qualified health-care professional according to facility-defined protocol. An anesthesiology record (if anesthesia is required) shall become part of the permanent medical record.

Guidance

Facilities that collect cellular therapy products by apheresis that are for further manufacturing by a clinical trial sponsor or manufacturer should ensure that they maintain a chain of custody that includes concurrent, permanent, auditable documentation illustrating the guardianship of the cell (or gene) therapy product.

For further information, refer to the guidance associated with Standards 5.1.2 and 6.2.3. (SS)

☑ Actionable Checklist

• Develop and maintain an SOP for documenting records of administration, including all required elements.
  • Include patient’s name and unique identifier(s) in the SOP.
  • Ensure donation identification number is recorded.
  • Document product description code, type of collection, and division code.
  • Record product name and attributes.
  • Include medical order for administration.
  • Confirm recipient and product identity before administration.
  • Record names and/or identifiers of persons who administered the product.
  • Document dates and times of product administration initiation and completion.
  • Capture all administration information, including patient’s vital signs and time of events.
  • Document any adverse events and reference appropriate documentation forms.
  • Record notification details if an adverse event occurred.
  • Ensure critical steps are entered into the permanent medical record by qualified health-care professionals.
  • Include anesthesiology record in the permanent medical record if anesthesia is required.
• Conduct regular audits to ensure compliance with the SOP for records of administration.
• Train staff on the SOP and document training records.
• Implement a review process for records of administration to ensure completeness and accuracy.
• Establish a CAPA process for addressing any deviations found during audits or reviews.

5.27.5 Patient Records

[F]

Patient records shall include the following:

1. Patient’s name and unique identifier(s).
2. Order for administration.
3. Donation identification number.
4. Product description code, type of collection, and division code.
5. Product name and attributes.
6. Medical and surgical history and physical examination.
7. If applicable, interpretation of tests for infectious disease markers.
8. Signed informed consent for administration of the cellular therapy product.
9. Unique cellular therapy product identifier(s).
10. If applicable, interpretation of ABO and other red cell antigen and Rh typings and, for allogeneic recipients, documentation of:
    a) The detection and identification of unexpected red cell antibodies.
    b) Assessment of blood grouping compatibility between the intended donor and recipient.
11. Documentation of HLA typing results, if indicated.
12. Other relevant testing records.

Guidance

#2 - The committee added new subnumber 2 requiring that patient records include the “order for administration” for completeness. (SC)

☑ Actionable Checklist

• Verify that patient records include the patient’s name and unique identifier(s).
• Ensure the order for administration is documented in the patient records.
• Record the donation identification number in the patient records.
• Include product description code, type of collection, and division code in patient records.
• Document product name and attributes in the patient records.
• Maintain records of medical and surgical history and physical examination.
• If applicable, include interpretation of tests for infectious disease markers.
• Obtain and document signed informed consent for administration of the cellular therapy product.
• Record unique cellular therapy product identifier(s) in the patient records.
• If applicable, document interpretation of ABO and other red cell antigen and Rh typings.
  • Include detection and identification of unexpected red cell antibodies.
  • Assess and document blood grouping compatibility between donor and recipient.
• Include documentation of HLA typing results, if indicated.
• Ensure all other relevant testing records are included in the patient records.

5.27.6

The facility shall have policies, processes, and procedures regarding the discharge and follow-up of patients after the administration procedure.

☑ Actionable Checklist

• Develop and document a comprehensive SOP for patient discharge and follow-up post-administration.
  • Include criteria for discharge readiness in the SOP.
  • Outline follow-up schedule and procedures in the SOP.
• Train staff on the discharge and follow-up SOP and document training records.
• Implement a patient discharge checklist to ensure all criteria are met before discharge.
• Maintain a log of all discharged patients and their follow-up appointments.
• Conduct regular audits of discharge and follow-up processes to ensure compliance.
• Review and update the discharge and follow-up SOP annually or as needed based on audit findings.

5.28 Postadministration Monitoring

The facility shall have policies, processes, and procedures for recipient follow-up, including the collection of outcome data following the administration of cellular therapy products, and to communicate this information with the procurement and/or processing facility. This shall include any immediate or late adverse event suspected to be linked to the cellular therapy product. Standard 7.3 applies.

Guidance

Postadministration monitoring is intended to address any immediate or late adverse events suspected to be linked to the product, such as hives, rash, difficulty breathing, etc. Delayed reactions or events may occur days or weeks after administration of the cell therapy product. Adverse events are described in the Circular of Information for the Use of Cellular Therapy Products. Clinical outcomes should be specific to the cellular therapy product and can include, but are not limited to, elements such as time to neutrophil and platelet engraftment, graft loss, or death before engraftment. (SS)

☑ Actionable Checklist

• Develop and implement SOPs for recipient follow-up post-cellular therapy administration.
  • Include procedures for collecting outcome data and monitoring for immediate or late adverse events.
  • Reference the Circular of Information for the Use of Cellular Therapy Products for adverse event descriptions.
• Establish a communication protocol to share outcome data and adverse events with the procurement and/or processing facility.
• Create and maintain a log for documenting all adverse events, including immediate and delayed reactions.
• Train staff on recognizing and reporting adverse events related to cellular therapy products.
  • Keep training records and competency evaluations up to date.
• Conduct regular audits of postadministration monitoring processes to ensure compliance with SOPs and standards.
• Review and update policies and procedures annually or as needed based on audit findings and new information.

5.28.1

When data are reported to a registry, the outcomes data shall be entered into the facility’s database in a manner to ensure that data can be queried, extracted, analyzed, and reported to stakeholders in a consistent manner.

Guidance

Collected data to be reported to a registry should be entered in the facility database. The latter shall be validated to maintain data integrity for further queries, data extraction and analysis, and reports to the stakeholders. Facilities should have a system in which outcome data, such as graft-vs-host disease, adverse events, and survival, can be compiled and reported to appropriate registry databases in a consistent, meaningful, and sustainable manner.

The facility shall have a validated process to maintain data integrity for further analysis, queries, data extraction and analysis, and reports to the stakeholders.

The facility should be able to demonstrate that all data are retrievable. (SS)

Reference Standard 5.6.2A — Requirements for Labeling of Cellular Therapy Products

(For labeling of regulated investigational products or licensed products, Standards 5.6.2.1 and 5.6.2.2 apply.)

Item No.	Element	Completion of Procurement1	In-Process Label1	Completion of Processing	Distribution and Issue2
1	Donation identification number (Unique alpha and/or numeric identifier of the product)3	P	P	P	P
2	Name of product	P	P	P	P
3	Product attributes4	A5	R	A5	P6
4	Product code3 Product description code Collection type code Division code	P	N/A	P	P
5	Unique donor identifier or name7	A	N/A	A5	A6
6	Date of procurement	A	N/A	A5	A6
7	Unique, traceable, chain-of identity identifier	P	P	P	P
8	Time of completion of procurement (time zone, if applicable)8	R	N/A	R	R
9	Name of procurement facility/donor registry	R	N/A	R	R
10	Approximate product volume or weight (if applicable)	R	N/A	R	R
11	Names/volumes of anticoagulants and other additives (if applicable)	R	N/A	A5	A6
12	Patient/recipient name and/or identifier (if known)9	R	R	R	A5
13	Expiration date and time (if applicable)	N/A	N/A	A10	A
14	ABO and Rh of the donor (if applicable)	N/A	N/A	R	R
15	CMV status of the donor (if applicable)	N/A	N/A	N/A	R
16	Red cell compatibility (if applicable)	N/A	N/A	N/A	R
17	Recommended storage temperature (in degrees Celsius)	R	N/A	A	A
18	Name and address of the facility that determines the product has met release criteria and makes the product available for distribution	N/A	N/A	N/A	R
19	Biohazard label (if applicable; see Reference Standard 5.6.2B, Requirements for Labeling Shipping Containers)	A	A5	A5	A5
20	Phrase: “Do Not Irradiate” (if applicable)	N/A	R	A5	A5
21	Phrase: “Do Not Use Leukoreduction Filters” (if applicable)	N/A	N/A	A5	A5
22	Phrase: “NOT EVALUATED FOR INFECTIOUS SUBSTANCES” and the statement “WARNING: Advise Patient of Communicable Disease Risks” (if applicable)	A	A5	A5	A5
23	Phrases: “WARNING: Reactive Test Results for [name of disease agent or disease]” and “WARNING: Advise Patient of Communicable Disease Risks” (if applicable)	A	A5	A5	A5
24	Phrase: “For Autologous Use Only” (if applicable)	A	A5	A5	A5
25	Phrase: “For Use by Intended Recipient Only” (if applicable)	N/A	A5	A5	A5
26	Phrase: “Properly Identify Intended Recipient and Product”	N/A	A5	A5	A5
27	Phrase: “CAUTION: New Drug – Limited by Federal (or United States) Law to Investigational Use” (if applicable)	N/A	N/A	N/A	A5
28	Phrase: “For Nonclinical Use Only” (if applicable)	N/A	R	A5	A5

¹The in-process label may be used during processing and before distribution and issue.
²The final labeling information for distribution shall be on or included with the container before the product is issued or transported.
³Standard 5.6.1 applies.
⁴Additional characteristics that uniquely define a cellular therapy product. A group of attributes, called Core Conditions, are required; these conditions include anticoagulant and/or additive, nominal collection volume, and storage temperature. Labeling terminology shall conform to current ICCBBA or Eurocode labeling requirements, as applicable.
⁵If affixing or attaching the applicable warnings and statements to the container is physically impossible, then the labeling must accompany the human cells, tissues, and cellular and tissue-based products.
⁶If label size precludes displaying all product attributes, the label shall refer to accompanying documentation for details.
⁷In cases where donor anonymity must be preserved, such as with products from unrelated-donor registries, this information is not required.
⁸Time zone: only applicable if the procurement facility is different from the processing facility.
⁹Ensure maintenance of the chain of identity.
¹⁰If expiration date is not affixed to cryopreserved products at the end of processing, then records of stability studies shall be available to demonstrate expiration date at release of the cryopreserved product.

A = attached (may be permanently affixed); CMV = cytomegalovirus; N/A = not applicable;
P = permanently affixed; R = accompanying records.

Reference Standard 5.6.2B — Requirements for Labeling Shipping Containers

Item No.	Element	Shipping Document*	Outer Shipping Container
1	Biohazard label (if applicable)	R	N/A
2	Phrase: “Do Not Irradiate” (if applicable)	R	A
3	Phrase: “Do Not X-Ray” (if applicable)	R	A
4	Phrases: “Medical Specimen” or “Human Cells for Transplantation” or equivalent	N/A	A
5	Date of distribution	R	R
6	Name and street address of receiving facility	R	A
7	Name and phone number of contact person at receiving facility	R	A

*Shipping document shall be placed within the shipping container.
A = affixed or attached using a tie-tag; N/A = not applicable; R = accompanying records.

Reference Standard 5.7.5A — Labeling and Packaging Requirements upon Shipping of Cellular Therapy Products

1. Summary of processing records; statement of donor eligibility determination; infectious disease testing results; and testing records, including name, address, and emergency contact information for shipping/issuing facility.¹
2. Warning label(s) for potentially toxic or volatile packing materials, including dry ice or liquid nitrogen.
3. Instructions for receiving and opening the container.
4. Current Circular of Information for the Use of Cellular Therapy Products, certificate of analysis, manufacturer’s insert, investigator’s brochure, or equivalent.²
5. Notification of biohazardous materials (see Standard 5.8.1).

¹21 CFR 1271.55(a), 21 CFR 1271.55(b), 21 CFR 1271.60(d)(2), 21 CFR 1271.65(b)(2), 21
CFR 1271.90(c), 21 CFR 1271.370(c), and 21 CFR 1271.265 (b).
²Includes, but is not limited to, a written description of the product.

Reference Standard 5.10A — General Requirements for Cellular Therapy Product Donors1

¹FDA Guidance: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and
Tissue-Based Products (HCT/Ps) (August 8, 2007).
21 CFR 1271.

Reference Standard 5.10B — Clinical Evaluation and Laboratory Testing of Living Allogeneic Donors

Reference Standard 5.10C — Clinical Evaluation and Laboratory Testing of Autologous Donors

Refernce Standard 5.10D — Clinical Evaluation and Laboratory Testing of Mothers of Cord Blood or Gestational Material Donors

Reference Standard 5.10E — Clinical Evaluation and Laboratory Testing of Cadaveric Donors

Reference Standard 5.15A — Processing Tests for HPC, Apheresis and HPC, Marrow

Reference Standard 5.15B — Processing Tests for HPC, Cord Blood Products or Gestational Materials

Reference Standard 5.15C — Processing Tests for Cellular Therapy Products Other than HPC, Apheresis; HPC, Marrow; and HPC, Cord Blood or Gestational Materials

Excerpt of Reference Standard 6.2.9A Relevant to Process Control

Standard	Record to Be Maintained	Quality System Records	Donor Eligibility/Management Issues	Unit/Recipient	Retention after Creation (C) or Final Disposition (F) of Related Product	Minimum Retention Time (in years)1
5.1.1	Validation of new or changed processes and procedures	X	X	X	C	10
5.1.2	Quality control records and review of quality control results	X	X	X	C	10
5.1.8	Identification and traceability of products	N/A	N/A	X	C	10
5.1.9.1	Supplier and/or consignee processes for traceability, tracking, and recall of products	X	X	X	C	10
5.1.9.1.1	Facility policy for the use/issue of a cellular therapy product provided by a supplier and/or received by a consignee that lacks a complete chain of custody	X	X	X	F	10
5.1.10	Participation in an external proficiency testing program	X	X	X	C	10
5.1.10.3	Proficiency testing results reviewed by the medical or laboratory director	X	X	X	C	10
5.2	Outcome data	X	X	X	F	10
5.2.4.1	Notification by patient-care service to issuing or processing facility of adverse events	N/A	N/A	X	F	10
5.3	Qualification of all materials used in the procurement, processing, and/or administration of cellular therapy products	X	X	X	C	10
5.3.2.1	Quarantine of critical materials	X	X	X	C	10
5.3.2.2	Complete records of the inspection of incoming materials that come into contact with the cellular therapy product or that directly affect the quality of the product	N/A	N/A	X	C	10
5.3.2.3	Identification of materials used on an emergency basis	N/A	N/A	X	C	10
5.3.4	Inspection of in-house reagents	N/A	N/A	X	C	10
5.3.5	Validation and monitoring of equipment, materials, and methods used in cleaning and sterilization of non-single-use materials	X	X	X	C	10
5.3.6	Use and identification of critical materials that come into contact with the patient or cellular therapy product	X	X	X	F	10
5.3.6.1	Package inserts, certificates of analysis, or any manufacturer’s documentation, including recall or defect notices, advisories, etc, for all critical materials used	X	X	X	C	10
5.4.2.1	Monitoring and review of the effectiveness of aseptic methods	N/A	N/A	X	C	10
5.4.3	Operational controls to prevent mix-up and contamination	X	X	X	C	10
5.5.1	Unique identification and traceability of cellular therapy products and samples from source to final disposition	N/A	N/A	X	C	10
5.6, #2,3, 5	Labeling controls	N/A	N/A	X	C	10
5.6.1	ISBT 128 implementation	N/A	N/A	X	C	10
5.6.3	Verification of product packaging and labeling	N/A	N/A	X	C	10
5.7	Transport of products	N/A	N/A	X	C	10
5.7.2	Qualification of shipping containers and periodic requalification	X	X	X	C	10
5.7.3	Monitoring of temperature for noncryopreserved products	N/A	N/A	X	F	10
5.7.3.1	Continuous monitoring of temperature for cryopreserved products	N/A	N/A	X	F	10
5.7.6	Product acceptance and shipper temperature upon receipt	N/A	N/A	X	C	10
5.8	Inspection and testing activities	X	X	X	C	10
5.8.1	Inspection of incoming cells, tissues, and organs	N/A	N/A	X	C	10
5.8.2	Inspection and testing of products during processing	N/A	N/A	X	C	10
5.9.1	Storage area temperature and humidity	X	X	X	C	10
5.9.1.1	If cellular therapy products are stored in an open storage area, the ambient temperature recorded at least every 4 hours	X	X	X	C	10
5.9.3, 5.9.4	Monitoring of temperature and/ or liquid nitrogen levels in storage devices and documentation of alarm activation	X	X	X	C	10
5.10	Determination of donor eligibility and verification that procurement criteria (eg, informed consent) have been met	N/A	X	N/A	F	10
5.10.2.2	Infectious disease testing of donors	N/A	X	N/A	F	10
5.10.2.3	Cadaveric donor eligibility	N/A	X	N/A	F	10
5.10.2.4	Donor testing performed	N/A	X	N/A	F	10
5.10.4	Review of donor screening and infectious disease testing record before international shipment or transport	N/A	X	N/A	F	10
5.10.5	Final determination of donor eligibility	N/A	X	N/A	F	10
5.10.6.2	Communication of abnormal results on medical history screening or testing that may affect the donor’s health	N/A	X	N/A	F	10
5.10.6.3	Communication of abnormal results on medical history screening or testing that may affect the recipient’s health or the therapeutic value of the cellular therapy product	N/A	X	N/A	F	10
5.10.6.4	Ineligible donors	N/A	X	N/A	C	10
5.10.7	Products from ineligible donors	N/A	X	N/A	F	10
5.10.8	Incomplete donor eligibility determination for donors not screened or tested	N/A	X	N/A	F	10
5.10.8.2	Physician notification of incomplete donor eligibility	N/A	X	N/A	C	10
5.11.2	Central venous access device placement by qualified individual or physician	N/A	X	N/A	C	10
5.11.3.1	Evaluation of allogeneic and autologous donors for the risk of hemoglobinopathy before the administration of a mobilizing agent	N/A	X	N/A	C	10
5.12.1	Medical orders for procurement	X	X	X	F	10
5.12.2.2, 5.12.2.4	Final approval and documentation by the donor’s physician (or by a health-care professional, if appropriate) that the donor is able to proceed with donation in conformance with Reference Standard 5.10A, General Requirements for Cellular Therapy Product Donors	N/A	X	N/A	F	10
5.12.2.3	For donors of mobilized cells (apheresis), a complete blood count obtained within 24 hours before each procurement procedure; for marrow donors, a complete blood count obtained before procurement	N/A	X	N/A	C	10
5.12.4	Confirmation of donor identity, at the time of procurement, by two identifiers	N/A	X	N/A	F	10
5.12.5	Identification numbers and expiration dates of lot numbers of all disposables and additives used in procurement	N/A	X	N/A	F	10
5.12.5, 5.12.6	Complete procurement record; review of procurement record	N/A	X	N/A	F	10
5.13	Definition of procurement goals	N/A	N/A	X	F	10
5.15.1	Medical orders for processing, preservation, or storage	X	X	X	F	10
5.15.2	Complete processing record; verification that acceptable values or ranges for defined critical characteristics for each product were obtained	N/A	N/A	X	F	10
5.15.3	Determination of acceptable values or ranges	N/A	N/A	X	C	10
5.15.4	Procedures used to manage red cell antigen incompatibility	N/A	N/A	X	F	10
5.16	Product-specific specifications and acceptable storage conditions of noncryopreserved products	N/A	N/A	X	C	10
5.17.2.1.1	Segment identification by two individuals	N/A	N/A	X	C	10
5.17.3	Complete cryopreservation records	N/A	N/A	X	F	10
5.18	Stability program for each type of cellular therapy product and expiration dates	X	X	X	C	10
5.19	Disposition of products consistent with informed consent and laws and regulations	X	X	X	F	10
5.20.2, 5.20.2.3	Review of donation criteria, final processing criteria, and final product-specified requirements	N/A	N/A	X	C	10
5.20.2, 5.20.3	Review of donation criteria, final processing criteria, and final product-specified requirements	N/A	N/A	X	F	10
5.21	Request for distribution	N/A	N/A	X	C	10
5.22	Product issue	N/A	N/A	X	F	10
5.22.1	Review of criteria for issue	N/A	N/A	X	F	10
5.22.4	Product return	N/A	N/A	X	F	10
5.22.5	Product reissue	N/A	N/A	X	F	10
5.24	Clinical care of the recipient	N/A	N/A	X	F	10
5.24.1.2	Medical orders for administration	X	X	X	F	10
5.25	Preparation of the recipient for administration of the cellular therapy product	N/A	N/A	X	F	10
5.26.2	Review of criteria for receipt	N/A	N/A	X	F	10
5.27	Confirmation of identity of the product and the intended recipient, using at least two identifiers	N/A	N/A	X	F	10
5.27.3	Identification of adverse events occurring during the infusion of final cellular therapy products and communication to the issuing facility	N/A	N/A	X	F	10
5.27.4	Records of administration	N/A	N/A	X	F	10
5.27.5	Complete administration record and recipient records	N/A	N/A	X	F	10

¹Applicable federal, state, or local law may exceed this period.

☑ Actionable Checklist

• Validate the database system to ensure data integrity for querying, extraction, analysis, and reporting.
  • Document the validation process and results in the Validation Master Plan (VMP).
• Develop and implement SOPs for entering outcomes data into the facility’s database.
  • Include procedures for data entry, verification, and validation.
• Conduct regular internal audits to verify compliance with data entry and reporting procedures.
  • Document audit findings and corrective actions in the quality records.
• Train staff on data entry procedures and ensure competency evaluations are up-to-date.
  • Maintain training records and competency evaluations in the personnel files.
• Implement a system for compiling and reporting outcome data to registry databases consistently.
  • Use crosswalk documents to map SOPs to AABB and FACT-JACIE standards.
• Ensure all reported data are retrievable and maintain a log of data retrieval requests and outcomes.