QSE 10 — Facilities and Safety

Key Concepts

Key Concepts: This QSE addresses the safety and adequacy of areas where the work required by these CT Standards is performed. This includes occupational safety, biohazardous material disposal, environmental monitoring, and compliance with applicable local and national regulations.

Key Terms
Environmental Monitoring: Policies, processes, and procedures used for monitoring any or all of the following: temperature, humidity, particulates, and microbial contamination in a specific area. Where appropriate, the program shall include sampling sites, frequency of sampling, and
investigative and corrective actions that should be followed when specified limits are exceeded.

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.

Organization: An institution, or a location or operational area within that organization; the entity assessed by the AABB and receiving AABB accreditation for specific activities.

Examples of Objective Evidence:

• Policies, processes, and procedures related to this chapter.
• Safe environmental conditions for all individuals in the organization.
• Local, state, and national regulations being followed.
• Proper discard of hazardous and potentially hazardous materials.
• Personal protective equipment (PPE) is available and in use.

10.0 Facilities and Safety

The organization shall ensure safe environmental conditions.The work area shall be suitable for the activities performed.Safety programs shall meet local, state, and national regulations.

Guidance

This standard requires that the facility ensure safe and adequate environmental conditions in the workplace. Specifically, this standard requires that the facility have a program that is designed to minimize risks to the health and safety of its employees, donors, volunteers, and patients. Implicit in this standard is the requirement that suitable quarters, environment, and equipment be available to maintain safe operations.

The standard specifically requires processes for biological, chemical, and radiation safety, where
applicable, as well as a system for monitoring training and compliance with those processes.
The standard also requires that products be handled and disposed of in a manner that is designed to prevent the potential for human exposure to infectious agents. Documentation of disposal of unused products should be maintained. (SS)

The committee revised standard 10.0 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop and implement a comprehensive safety program that meets local, state, and national regulations.
  • Create SOPs for biological, chemical, and radiation safety.
  • Establish procedures for the safe handling and disposal of products to prevent human exposure to infectious agents.
• Conduct a risk assessment of the work area to ensure it is suitable for activities performed.
  • Document findings and implement corrective actions as needed.
• Implement a system for monitoring training and compliance with safety processes.
  • Maintain records of training sessions and competency evaluations.
• Schedule regular internal audits to ensure continuous compliance with safety standards.
  • Document audit findings and track CAPAs to closure.
• Maintain a log of disposal of unused products, ensuring documentation is complete and accurate.

10.1 Safe Environment

The organization shall minimize and respond to environmentally related risks to the health and  safety of all individuals and products or services. Suitable quarters, environment, and equipment shall be available to maintain safe operations.

Guidance

The committee revised standard 10.1 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Conduct a risk assessment to identify potential environmental hazards in the facility.
  • Document findings and implement mitigation strategies.
• Develop and maintain SOPs for maintaining a safe environment, including emergency procedures.
• Ensure all equipment is regularly inspected and maintained according to manufacturer guidelines.
  • Keep detailed maintenance logs for each piece of equipment.
• Conduct regular training sessions on safety protocols for all staff.
  • Maintain records of training attendance and competency evaluations.
• Perform routine internal audits to verify compliance with safety standards.
  • Document audit findings and implement corrective actions as needed.
• Establish a system for reporting and addressing safety incidents or near misses.
  • Review incident reports in management reviews and update procedures accordingly.

10.1.1

Policies, processes, and procedures shall identify and address the hazards present in the facility—including biological, chemical, and, where applicable, radiation safety—and appropriate intervention to limit exposure. The facility shall maintain a system for monitoring training and compliance.

☑ Actionable Checklist

• Develop and implement SOPs for identifying and addressing biological, chemical, and radiation hazards.
  • Include specific intervention measures to limit exposure in SOPs.
• Conduct a comprehensive risk assessment to identify potential hazards in the facility.
• Establish a monitoring system to track training and compliance with safety protocols.
  • Maintain a log of training sessions and attendance records.
• Schedule regular safety audits to ensure adherence to safety policies and procedures.
• Document all identified hazards and corrective actions taken in a safety log.
• Review and update safety policies and procedures annually or as needed.

10.1.2

Biohazardous materials shall be handled and discarded in a manner that minimizes the potential for human exposure to infectious agents.

☑ Actionable Checklist

• Develop and implement an SOP for handling and disposal of biohazardous materials.
  • Include procedures for labeling, storage, and transport of biohazardous materials.
• Train all personnel on the SOP for biohazardous material handling and disposal.
  • Document training sessions and maintain records in the training log.
• Conduct regular audits to ensure compliance with biohazardous material handling procedures.
  • Use a checklist to verify adherence to SOPs during audits.
• Maintain a log of all biohazardous waste disposals, including date, type, and method of disposal.
• Review and update the SOP annually or as needed based on audit findings or regulatory changes.
• Ensure availability and proper use of personal protective equipment (PPE) for handling biohazardous materials.

10.1.3

Where liquid nitrogen is present, specific hazards shall be addressed.

☑ Actionable Checklist

• Conduct a risk assessment for liquid nitrogen hazards and document findings.
  • Review and update SOPs related to liquid nitrogen handling and storage.
• Ensure all staff handling liquid nitrogen are trained and competency is evaluated annually.
  • Maintain training records and competency evaluations in personnel files.
• Install and maintain oxygen level monitoring systems in areas where liquid nitrogen is used.
  • Conduct and document regular checks and calibrations of monitoring systems.
• Implement emergency procedures for liquid nitrogen spills and exposure.
  • Conduct regular drills and document outcomes and improvements.
• Provide and maintain appropriate personal protective equipment (PPE) for handling liquid nitrogen.
  • Conduct regular inspections of PPE and replace as necessary.
• Document all incidents and near-misses involving liquid nitrogen and implement CAPAs as needed.

10.1.3.1

The facility shall have a system in place to monitor oxygen levels and an alarm system set to activate under conditions that will allow action to be taken.

Guidance

Adverse health effects begin when the oxygen level of air reaches “oxygen-deficient” levels of below 19.5% oxygen. Between 16% and 19.5%, symptoms can include increased breathing rates, accelerated heartbeat, impaired thinking, and poor coordination.

To be effective, the system should monitor continuously and activate both audible and visual alarms under conditions that will allow action to be taken before there are adverse consequences to humans in the area.

Refer to regulations defined by the local Competent Authority. (SS)

10.1.3.1.1

[Cord blood applicable]

Alarm activation shall require personnel to investigate and document the condition activating the alarm and to take immediate corrective action as necessary.

Guidance

Adverse health effects begin when the oxygen level of air reaches “oxygen-deficient” levels of below 19.5% oxygen. Between 16% and 19.5%, symptoms can include increased breathing rates, accelerated heartbeat, impaired thinking, and poor coordination.

To be effective, the system should monitor continuously and activate both audible and visual alarms under conditions that will allow action to be taken before there are adverse consequences to humans in the area.

Refer to regulations defined by the local Competent Authority. (SS)

☑ Actionable Checklist

• Install and maintain a continuous oxygen level monitoring system with both audible and visual alarms.
  • Verify that the alarm system activates when oxygen levels fall below 19.5%.
• Develop and implement an SOP for responding to oxygen level alarms, including investigation and documentation procedures.
• Train all relevant personnel on the SOP for oxygen alarm response and document training records.
• Conduct regular drills to ensure staff can effectively respond to oxygen deficiency alarms.
• Perform and document regular maintenance checks on the oxygen monitoring and alarm systems.
• Review and update the oxygen monitoring SOP and training materials annually or as needed.

10.1.4 Environmental Controls

[Cord blood applicable]

The facility shall design, approve, and implement an environmental control system that:

1. Optimizes donor, patient, and employee safety.
2. Ensures product integrity and safety.
3. Monitors cleaning or sanitation processes to minimize and mitigate contamination or accidental exposure to infectious disease agents.

Guidance

#3 - The committee edited standard 10.1.4 for completeness and clarity through the inclusion of the clause, “Monitors cleaning or sanitation processes to…” (SC)

☑ Actionable Checklist

• Develop and document an environmental control SOP that includes safety measures for donors, patients, and employees.
  • Reference SOP: ENV-001 Environmental Control Procedures.
• Implement a system to ensure product integrity and safety through environmental monitoring.
  • Use Form: ENV-002 Environmental Monitoring Log.
• Establish a cleaning and sanitation schedule with documented procedures to prevent contamination.
  • Reference SOP: CLN-001 Cleaning and Sanitation Procedures.
• Conduct regular audits of the environmental control system to verify compliance and effectiveness.
  • Use Form: AUD-003 Environmental Control Audit Checklist.
• Maintain records of all environmental monitoring and cleaning activities for review.
  • Use Log: ENV-003 Environmental Activity Log.
• Train staff on environmental control procedures and document training completion.
  • Reference Training Record: TRN-004 Environmental Control Training Log.

10.1.4.1

[Cord blood applicable]

The degree of environmental monitoring and controls shall be specific to the cellular therapy product manipulation performed.

Guidance

For “351 HCT/Ps,” regulated as drugs, clean-room certification must be maintained according to ISO 14644 (International Organization for Standardization) and GMP standards based on risk level. Critical processes require Grade A/ISO 5 areas with a maximum of 3520 particles 0.5 microns per m3.

Required monitoring components and frequencies:

1. Environmental controls:
   -Temperature, humidity, differential pressure monitoring.
   -HEPA (high-efficiency particulate air) filter integrity testing.
   -Air exchange rates verification.
   -Airflow visualization studies.
2. Particle monitoring:
   -Continuous monitoring during critical operations.
   -Particle counts per ISO classification limits.
   -Regular verification of HEPA filter performance.
3. Microbiological monitoring:
   -Active air sampling (action level: 1 CFU/m3 for ISO 5).
   -Surface monitoring with contact plates.
   -Personnel monitoring during operations.

Requalification schedule:

• Grade A/B areas: every 6 months.
• Grade C/D areas: annually.

Facilities must maintain complete documentation of monitoring results and implement immediate corrective actions for deviations. Changes affecting product safety, identity, purity, or potency require validation before implementation.

References

1. Tanna J, McCann CD, Smith R, et al. Environmental monitoring of current good manufacturing practices cleanroom facilities for manufacturing of cellular therapy products in an academic hospital setting. Cytotherapy 2024;26:1421-8.
2. US Food and Drug Administration. Guidance for industry: Sterile drug products produced by aseptic processing - current good manufacturing practice. Silver Spring, MD: CBER Office of Communication, Outreach, and Development, 2004.
3. International Organization for Standardization. ISO 14644-1:2015. Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness by particle concentration. Geneva: ISO, 2015.
4. International Organization for Standardization. ISO 14644-2:2015. Cleanrooms and associated controlled environments - Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration. Geneva: ISO, 2015.
5. International Organization for Standardization. ISO 14644-3:2019. Cleanrooms and associated controlled environments - Part 3: Test methods. Geneva: ISO, 2019.
6. International Organization for Standardization. ISO 14644-4:2022. Cleanrooms and associated controlled environments - Part 4: Design, construction and start-up. Geneva: ISO, 2022. (SS)

☑ Actionable Checklist

• Develop and implement SOPs for environmental monitoring specific to cellular therapy product manipulation.
  • Include procedures for temperature, humidity, and differential pressure monitoring.
  • Define HEPA filter integrity testing and air exchange rates verification.
  • Detail airflow visualization studies.
• Establish a particle monitoring program with continuous monitoring during critical operations.
  • Ensure particle counts comply with ISO classification limits.
  • Regularly verify HEPA filter performance.
• Implement microbiological monitoring protocols.
  • Conduct active air sampling with action levels set at 1 CFU/m3 for ISO 5.
  • Perform surface monitoring using contact plates.
  • Monitor personnel during operations.
• Schedule requalification of Grade A/B areas every 6 months and Grade C/D areas annually.
• Maintain complete documentation of all monitoring results.
  • Implement immediate corrective actions for deviations.
• Validate any changes affecting product safety, identity, purity, or potency before implementation.

10.1.5

The clinical facility shall have either on-site or ready access to services to manage anticipated adverse events and provide emergency medical care.

☑ Actionable Checklist

• Verify that the facility has a documented agreement with a nearby hospital for emergency medical services.
  • Review and update the agreement annually.
• Ensure that emergency contact numbers are posted in all relevant areas.
• Conduct quarterly drills to simulate emergency scenarios and document outcomes.
• Maintain an up-to-date list of staff trained in basic life support (BLS) and advanced cardiac life support (ACLS).
• Review and update SOPs related to managing adverse events and emergencies.
• Document all adverse events and emergency responses in the incident log.

10.2

[Cord blood applicable]

The organization shall monitor adherence to biological, chemical, and radiation safety standards and regulations.

Guidance

The committee added standard 10.2 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for monitoring compliance with biological, chemical, and radiation safety standards.
  • Reference applicable safety regulations and standards in the SOP.
• Conduct regular safety audits to assess adherence to safety protocols.
  • Use a standardized safety audit checklist.
• Maintain a log of all safety incidents and corrective actions taken.
• Ensure all personnel receive training on safety protocols and document completion.
  • Keep training records updated and accessible.
• Review and update safety protocols annually or as regulations change.
• Schedule and document management reviews of safety compliance at least annually.

10.3 Handling and Discarding of Biological Materials

[Cord blood applicable]

Biological materials shall be handled and discarded in a manner that minimizes the potential for human exposure to infectious agents.

Guidance

The committee added standard 10.3 based on updates to the AABB Quality System Essentials. (SC)

☑ Actionable Checklist

• Develop and implement an SOP for the handling and discarding of biological materials, ensuring compliance with safety regulations.
  • Include procedures for using personal protective equipment (PPE) when handling biological materials.
  • Outline steps for proper labeling and storage of biological materials to prevent accidental exposure.
• Train all personnel on the SOP for handling and discarding biological materials, with documented training records.
• Conduct regular audits to ensure compliance with the SOP and identify areas for improvement.
• Maintain a log of all biological materials discarded, including date, type of material, and method of disposal.
• Implement a system for reporting and documenting any incidents of exposure or near-misses related to biological materials.
• Review and update the SOP annually or as needed based on changes in regulations or facility practices.

10.4 General Operational Controls

Access to facilities used for procurement, processing, preservation, and storage shall be limited to authorized individuals.

Excerpt of Reference Standard 6.2.9A Relevant to Facilities and Safety

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
10.1.3.1.1	Alarm investigation	X	X	X	C	10
10.1.4, #3	Cleaning or sanitation processes	X	X	X	C	10
10.1.4.1	Environmental monitoring	X	X	X	C	10
10.2	Monitoring of biological, chemical, and radiation safety	X	X	X	C	10
10.3	Appropriate discard of products	X	X	X	C	10

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

☑ Actionable Checklist

• Restrict facility access to authorized personnel through badge or keycard systems.
  • Maintain an access log to record entry and exit of personnel.
• Develop and implement SOPs for alarm investigation and document all findings.
  • Retain alarm investigation records for a minimum of 10 years.
• Establish cleaning and sanitation SOPs for all facility areas.
  • Document each cleaning event and retain records for 10 years.
• Conduct regular environmental monitoring as per SOPs.
  • Keep environmental monitoring records for at least 10 years.
• Implement a monitoring system for biological, chemical, and radiation safety.
  • Document safety checks and retain records for 10 years.
• Create SOPs for the appropriate discard of products.
  • Retain discard records for a minimum of 10 years.