CM9 CELLULAR THERAPY PRODUCT STORAGE
CM9.1 Marrow Collection Facilities shall establish policies for the duration and conditions of storage prior to distribution to a Processing Facility or Clinical Program.
CM10 CELLULAR THERAPY PRODUCT TRANSPORTATION AND SHIPPING
CM10.1 Procedures for transportation and shipping of the cellular therapy product shall be designed to protect the integrity of the product and the health and safety of facility personnel.
CM10.1.1 The primary cellular therapy product container shall be placed in a secondary container that is sealed to prevent leakage.
CM10.1.2 The cellular therapy product shall be transported and/or shipped to the Processing Facility at a temperature defined in the transportation and shipping procedure.
CM10.1.3 Cellular therapy products that are transported and/or shipped from the collection site to any non-contiguous Processing Facility shall be transported and/or shipped in an outer container made of material adequate to withstand leakage of contents, impact shocks, pressure changes, temperature changes, puncture, and other conditions incident to ordinary handling.
CM10.1.4 If the intended recipient has received high-dose therapy, the cellular therapy product shall be transported by a qualified courier.
CM10.2 The cellular therapy product shall be transported and/or shipped with required accompanying records as defined in the transportation and shipping procedure and in compliance with CM7.6.
CM10.3 There shall be a record of the date and time of cellular therapy product distribution.
CM11 RECORDS
CM11.1 The Marrow Collection Facility shall comply with B10 if it operates independently of a Clinical Program.
CM12 DIRECT DISTRIBUTION TO CLINICAL PROGRAM
CM12.1 Where cellular therapy products are distributed directly from the Marrow Collection Facility to the Clinical Program for administration or subsequent processing, the Standards related to labeling, documentation, distribution, transportation, and recordkeeping in Sections D7, D8, D10, D12, and the Appendices apply.
PART C: APHERESIS COLLECTION FACILITY STANDARDS
C1 General
C2 Apheresis Collection Facility
C3 Personnel
C4 Quality Management
C5 Policies and Procedures
C6 Allogeneic and Autologous Donor Evaluation and Management
C7 Coding and Labeling of Cellular Therapy Products
C8 Process Controls
C9 Cellular Therapy Product Storage
C10 Cellular Therapy Product Transportation and Shipping
C11 Records
C12 Direct Distribution to Clinical Program
PART C: APHERESIS COLLECTION FACILITY STANDARDS
C1 GENERAL
C1.1 These Standards apply to the Apheresis Collection Facility for collection activities of all cellular therapy products collected from living donors.
C1.2 The Apheresis Collection Facility shall use cell processing facilities that meet FACT-JACIE Standards with respect to their interactions with the Apheresis Collection Facility.
C1.3 The Apheresis Collection Facility shall abide by all applicable laws and regulations.
C1.3.1 The Apheresis Collection Facility shall be licensed, registered, and/or accredited as required by the appropriate governmental authority for the activities performed.
C1.4 For initial accreditation, the Apheresis Collection Facility, including an Apheresis Collection Facility Director, an Apheresis Collection Facility Medical Director, and at least one staff member, shall have been in place and performing cellular therapy product collections for at least twelve (12) months preceding accreditation.
C1.4.1 A minimum of ten (10) cellular therapy products shall have been collected by apheresis in the twelve (12) months preceding accreditation.
C1.5 The Apheresis Collection Facility shall collect a minimum average of ten (10) cellular therapy products by apheresis per year within the accreditation cycle.
C2 APHERESIS COLLECTION FACILITY
C2.1 There shall be appropriate designated areas for collection of cellular therapy
products, for the product collected, and for storage of supplies, reagents, and
equipment.
C2.1.1 The Apheresis Collection Facility shall be divided into defined areas of adequate size to prevent improper labeling, mix-ups, contamination, or cross-contamination of cellular therapy products.
C2.1.2 There shall be a process to control storage areas to prevent mix-ups, contamination, and cross-contamination of all products prior to release or distribution.
C2.1.3 There shall be suitable space for confidential donor examination and evaluation.
C2.2 The Apheresis Collection Facility shall provide adequate lighting, ventilation, and access to sinks to prevent the introduction, transmission, or spread of communicable disease.
C2.3 Critical Apheresis Collection Facility parameters that may affect cellular therapy product viability, integrity, contamination, sterility, or cross-contamination during collection shall be identified, controlled, monitored, and recorded to demonstrate
ongoing compliance.
C2.3.1 When using collection methods that may result in contamination or crosscontamination of cellular therapy products, critical environmental conditions shall be controlled where appropriate for temperature, humidity, ventilation, air quality, and surface contaminates.
C2.3.2 Apheresis Collection Facility parameters and environmental conditions shall be controlled to ensure the safety and comfort of patients, donors, and personnel.
C2.4 The Apheresis Collection Facility shall be maintained in a clean, sanitary, and orderly manner.
C2.4.1 There shall be documentation of facility cleaning and sanitation to ensure adequate conditions for proper operations.
C2.5 There shall be adequate equipment and materials for the procedures performed.
C2.6 There shall be access to autologous and/or CMV-appropriate and irradiated blood products.
C2.7 There shall be access to an intensive care unit and/or emergency services.
C2.8 SAFETY REQUIREMENTS
C2.8.1 The Apheresis Collection Facility shall be operated in a manner designed to minimize the risks to the health and safety of employees, patients, donors, visitors, and volunteers.
C2.8.2 The Apheresis Collection Facility shall have a written safety manual that includes instructions for action in case of exposure to communicable disease or to chemical, biological, or radiological hazards, where applicable.
C3 PERSONNEL
C3.1 APHERESIS COLLECTION FACILITY DIRECTOR
C3.1.1 There shall be an Apheresis Collection Facility Director who is an individual with a medical degree or degree in a relevant science, qualified by postgraduate training or experience for the scope of activities carried out in the Apheresis Collection Facility. The Apheresis Collection Facility Director may also serve as the Apheresis Collection Facility Medical Director, if appropriately credentialed.
C3.1.2 The Apheresis Collection Facility Director shall be responsible for all technical procedures, performance of the collection procedure, supervision of staff, administrative operations, and the Quality Management Program, including compliance with these Standards and other applicable laws and regulations.
C3.1.3 The Apheresis Collection Facility Director shall have at least one year experience in cellular therapy product collection procedures.
C3.1.3.1 The Apheresis Collection Facility Director shall have performed or supervised a minimum of four (4) cellular therapy product apheresis collection procedures in the twelve (12) months preceding accreditation and a minimum average of
four (4) cellular therapy product apheresis collection procedures per year within the accreditation cycle.
C3.1.4 The Apheresis Collection Facility Director shall participate regularly in educational activities related to cellular therapy product collection and/or transplantation.
C3.2 APHERESIS COLLECTION FACILITY MEDICAL DIRECTOR
C3.2.1 There shall be an Apheresis Collection Facility Medical Director who is a licensed or certified physician with postgraduate training in cell collection and/or transplantation. The Apheresis Collection Facility Medical Director may also serve as the Apheresis Collection Facility Director, if appropriately credentialed.
C3.2.2 The Apheresis Collection Facility Medical Director or designee shall be responsible for the medical care of patients undergoing apheresis, including the pre-collection evaluation of the donor at the time of donation and care of any complications resulting from the collection procedure.
C3.2.3 The Apheresis Collection Facility Medical Director shall have at least one year experience in cellular therapy product collection procedures.
C3.2.3.1 The Apheresis Collection Facility Medical Director shall have performed or supervised a minimum of four (4) cellular therapy
product apheresis collection procedures in the twelve (12) months preceding accreditation and a minimum average of four (4) cellular therapy product apheresis collection procedures per year within the accreditation cycle.
C3.2.4 The Apheresis Collection Facility Medical Director shall participate regularly in educational activities related to cellular therapy product collection and/or transplantation.
C3.3 QUALITY MANAGEMENT SUPERVISOR
C3.3.1 There shall be an Apheresis Collection Facility Quality Management Supervisor approved by the Apheresis Collection Facility Director to establish and maintain systems to review, modify, and approve all policies and procedures intended to monitor compliance with these Standards and/or the performance of the Apheresis Collection Facility.
C3.3.2 The Apheresis Collection Facility Quality Management Supervisor shall participate regularly in educational activities related to the field of cellular therapy, cell collection, and/or quality management.
C3.4 STAFF
C3.4.1 There shall be adequate numbers of trained collection personnel available in the Apheresis Collection Facility.
C3.4.2 For Apheresis Collection Facilities collecting cellular therapy products from pediatric donors, physicians and collection staff shall have documented training and experience in performing these procedures.
C4 QUALITY MANAGEMENT
C4.1 The Apheresis Collection Facility shall establish and maintain a written Quality Management Plan.
C4.2 The Quality Management Plan shall include an organizational chart of key positions, personnel, and functions within the Apheresis Collection Facility.
C4.2.1 The Quality Management Plan shall include a description of how these key personnel interact to implement the quality management activities.
C4.2.2 There shall be an Apheresis Collection Facility Director or designee who is responsible for the Quality Management Plan as it pertains to the Apheresis Collection Facility.
C4.2.2.1 The Apheresis Collection Facility Director or designee shall have authority over and responsibility for ensuring that the Quality Management Program is effectively established and maintained.
C4.2.2.2 The Apheresis Collection Facility Director or designee shall not have oversight of his/her own work if this person also performs other tasks in the Apheresis Collection Facility.
C4.2.2.3 The Apheresis Collection Facility Director or designee shall report on quality management activities, at a minimum,
quarterly.
C4.2.2.4 The Apheresis Collection Facility Director or designee shall report on the performance of the Quality Management Plan, at a minimum, annually. This report shall also be provided to the Clinical Program Director, as applicable.
C4.3 The Quality Management Plan shall include, or summarize and reference, personnel education, experience, and training requirements for each key position in the Apheresis Collection Facility. Personnel requirements shall include at a minimum:
C4.3.1 Current job description for all staff.
C4.3.2 A system to document the following for each staff member:
C4.3.2.1 Initial qualifications.
C4.3.2.2 Orientation.
C4.3.2.3 Initial training.
C4.3.2.4 Competency for each critical function performed.
C4.3.2.5 Continued competency at least annually.
C4.3.2.6 Training and retraining.
C4.3.2.7 Provisions for continuing education.
C4.3.3 A description of minimal trainer qualifications and a uniform plan for staff
training.
C4.4 The Quality Management Plan shall include, or summarize and reference, policies and procedures for development, approval, validation, implementation, review, revision, and archival for all critical processes, policies, and procedures.
C4.5 The Quality Management Plan shall include, or summarize and reference, a system for document control. The document control system shall include at a minimum the following elements:
C4.5.1 Listing of all active critical documents that shall adhere to the document control system requirements. Controlled documents shall include at a minimum:
C4.5.1.1 Policies
C4.5.1.2 Standard Operating Procedures.
C4.5.1.3 Worksheets.
C4.5.1.4 Forms.
C4.5.1.5 Labels.
C4.5.2 A procedure for preparation, approval, implementation, review, revision, and archival of all policies and procedures.
C4.5.2.1 Archived policies and procedures, the inclusive dates of use, and their historical sequence shall be maintained for a minimum of ten (10) years from archival or according to governmental or institutional policy, whichever is longer.
C4.5.3 A standardized format for policies, procedures, worksheets, forms, and labels.
C4.5.4 Assignment of numeric or alphanumeric identifier and title to each document and document version regulated within the system.
C4.5.5 A procedure for document approval, including the approval date, signature of approving individual(s), and the effective date.
C4.5.6 A system to ensure that controlled documents cannot undergo accidental or unauthorized modification.
C4.5.7 A system for document change control that includes a description of the change, the signature of the approving individual(s), approval date, and effective date.
C4.5.8 A system for the retraction of obsolete documents to prevent unintended use.
C4.5.9 A system for record creation, assembly, review, storage, archival, and retrieval.
C4.6 The Quality Management Plan shall include, or summarize and reference, policies and procedures for establishment and maintenance of written agreements with third parties whose services impact the cellular therapy product.
C4.6.1 Agreements shall include the responsibility of the facility performing any step in collection, processing, or testing to comply with applicable laws and regulations and these Standards.
C4.6.2 Agreements shall be dated, reviewed, and renewed on a regular basis.
C4.7 The Quality Management Plan shall include, or summarize and reference, policies and procedures for documentation and review of outcome analysis and product efficacy, as appropriate, including at least:
C4.7.1 For HPC products intended for hematopoietic reconstitution, a process for documentation and review of time to engraftment following product administration.
C4.7.2 For other cellular therapy products, the criteria for product efficacy and/or the clinical outcome shall be determined and shall be reviewed at regular time intervals.
C4.8 The Quality Management Plan shall include, or summarize and reference, policies, procedures, and a timetable for conducting, reviewing, and reporting audits of the Apheresis Collection Facility’s activities to verify compliance with elements of the Quality Management Program and operational policies and procedures.
C4.8.1 Audits shall be conducted on a regular basis by an individual with sufficient expertise to identify problems, but who is not solely responsible for the process being audited.
C4.8.2 The results of audits shall be used to recognize problems, detect trends, identify improvement opportunities, and implement corrective actions when necessary.
C4.8.3 Audits shall include, at a minimum:
C4.8.3.1 Documentation of proper donor eligibility determination prior to start of collection procedure.
C4.8.3.2 Documentation that external facilities performing critical contracted services have met the requirements of the written agreements.
C4.9 The Quality Management Plan shall include, or summarize and reference, policies and procedures on the management of cellular therapy products with positive microbial culture results that address at a minimum:
C4.9.1 Notification of the recipient’s physician.
C4.9.2 Investigation of cause.
C4.9.3 Follow-up of the donor, if relevant.
C4.10 The Quality Management Plan shall include, or summarize and reference, policies and procedures for errors, accidents, adverse events, biological product deviations, and complaints.
C4.10.1 Policies and procedures shall include methods for:
C4.10.1.1 Detection.
C4.10.1.2 Investigation.
C4.10.1.3 Evaluation.
C4.10.1.4 Documentation.
C4.10.1.5 Reporting.
C4.10.1.6 Corrective action.
C4.10.1.7 Follow-up for effectiveness of corrective action.
C4.10.2 Documentation of each adverse event that occurs in the Apheresis Collection Facility shall be reviewed in a timely manner by the
Apheresis Collection Facility Director and/or Apheresis Collection Facility Medical Director, as appropriate.
C4.10.3 A written description of adverse events shall be made available to the donor’s physician, the recipient’s physician, and the Processing Facility, if appropriate.
C4.10.4 When applicable, adverse events shall be reported to appropriate regulatory agencies within the required time frames.
C4.10.5 Deviations from Standard Operating Procedures shall be documented.
C4.10.5.1 Planned deviations shall be pre-approved by the Apheresis Collection Facility Director or designee.
C4.10.5.2 Unplanned deviations and associated corrective actions shall be reviewed by the Apheresis Collection Facility Director or designee.
C4.10.6 There shall be a defined process improvement plan that includes policies or procedures for the recognition and investigation of the cause of all issues that require corrective action.
C4.10.6.1 The implementation of corrective actions shall include both short-term action to address the immediate problem and longterm action to prevent the problem’s recurrence.
C4.10.6.2 Follow-up activities shall be conducted to determine if the corrective actions were effective.
C4.11 The Quality Management Plan shall include, or summarize and reference, policies and procedures for cellular therapy product tracking and tracing that allow tracking from the donor to the recipient or final disposition and tracing from the recipient or final disposition to the donor.
C4.12 The Quality Management Plan shall include, or summarize and reference, policies and procedures for actions to take in the event the Apheresis Collection Facility’s operations are interrupted.
C4.13 The Quality Management Plan shall include, or summarize and reference, policies and procedures for qualification of critical reagents, supplies, equipment, and facilities.
C4.14 The Quality Management Plan shall include, or summarize and reference, policies and procedures for validation and/or verification of critical procedures.
C4.14.1 Critical procedures shall include at least the following: collection procedures, labeling, storage, and distribution.
C4.14.2 Changes to a process shall be verified or validated to ensure that they do not create an adverse impact anywhere in the operation.
C5 POLICIES AND PROCEDURES
C5.1 The Apheresis Collection Facility shall establish and maintain policies and/or procedures addressing critical aspects of operations and management in addition to those required in C4. These documents shall include all elements required by these Standards and shall address at a minimum:
C5.1.1 Donor and recipient confidentiality.
C5.1.2 Donor consent.
C5.1.3 Donor treatment.
C5.1.4 Donor screening, testing, and eligibility determination.
C5.1.5 Management of donors, including pediatric donors if applicable.
C5.1.6 Product collection.
C5.1.7 Labeling (including associated forms and samples).
C5.1.8 Product expiration dates.
C5.1.9 Product storage.
C5.1.10 Release and exceptional release.
C5.1.11 Transportation and shipping to include methods and conditions to be used for distribution to external facilities.
C5.1.12 Reagent and supply management.
C5.1.13 Equipment operation, maintenance, and monitoring to include corrective actions in the event of failure.
C5.1.14 Cleaning and sanitation procedures to include identification of the individuals responsible for the activities.
C5.1.15 Disposal of medical and biohazard waste.
C5.1.16 Facility management and monitoring.
C5.1.17 Emergency and disaster plan, including the Apheresis Collection Facility response.
C5.2 The Apheresis Collection Facility shall maintain a Standard Operating Procedures Manual.
C5.2.1 The Standard Operating Procedures Manual shall include a listing of all current Standard Operating Procedures.
C5.3 Standard Operating Procedures shall be sufficiently detailed and unambiguous to allow qualified technical staff to follow and complete the procedures successfully. Each individual procedure shall include:
C5.3.1 A clearly written description of the objectives.
C5.3.2 A description of equipment and supplies used.
C5.3.3 Acceptable end-points and the range of expected results, where applicable.
C5.3.4 A step wise description of the procedure.
C5.3.5 Reference to other Standard Operating Procedures or policies required to perform the procedure.
C5.3.6 A reference section listing appropriate literature, if applicable.
C5.3.7 Documented approval of each procedure by the Apheresis Collection Facility Director or Medical Director, as appropriate, prior to implementation and every two years thereafter.
C5.3.8 Documented approval of each procedural modification by the Apheresis Collection Facility Director or designated physician prior to implementation.
C5.3.9 A current version of orders, worksheets, reports, labels, and forms, where applicable.
C5.4 Copies of Standard Operating Procedures relevant to processes being performed shall be readily available to the facility staff.
C5.5 All personnel in the Apheresis Collection Facility shall follow the Standard Operating Procedures related to their positions.
C5.6 Review and/or training by a staff member shall be documented before the staff member is allowed to perform new and revised policies and procedures.
C5.7 There shall be a process to address age-specific issues in the Standard Operating Procedures as appropriate.
C6 ALLOGENEIC AND AUTOLOGOUS DONOR EVALUATION AND MANAGEMENT
C6.1 There shall be written criteria for allogeneic and autologous donor evaluation and management by trained medical personnel.
C6.2 ALLOGENEIC AND AUTOLOGOUS DONOR INFORMATION AND CONSENT FOR COLLECTION
C6.2.1 The collection procedure shall be explained in terms the donor can understand, and shall include the following information at a minimum:
C6.2.1.1 The risks and benefits of the procedure.
C6.2.1.2 Tests and procedures performed on the donor to protect the health of the donor and the recipient.
C6.2.1.3 The rights of the donor and parent of the donor who is a minor to review the results of such tests according to applicable laws and regulations.
C6.2.1.4 Protection of medical information and confidentiality.
C6.2.2 The donor shall have an opportunity to ask questions.
C6.2.3 The donor shall have the right to refuse to donate.
C6.2.3.1 The allogeneic donor shall be informed of the potential consequences to recipient of such refusal.
C6.2.4 Donor informed consent for the cellular therapy product collection shall be obtained and documented by a licensed health care professional familiar with the collection procedure.
C6.2.4.1 Informed consent from the allogeneic donor should be obtained by a licensed health care professional other than the intended recipient’s primary transplant physician.
C6.2.5 In the case of a minor donor, informed consent shall be obtained from the donor’s parent or legal guardian in accordance with applicable laws and regulations and shall be documented.
C6.2.6 The allogeneic donor shall give informed consent and authorization in advance to release the donor’s health information to the transplant physician and/or the recipient as appropriate.
C6.2.7 Documentation of consent shall be available to the Apheresis Collection Facility staff prior to the collection procedure.
C6.3 ALLOGENEIC AND AUTOLOGOUS DONOR SUITABILITY FOR CELLULAR
THERAPY PRODUCT COLLECTION
C6.3.1 There shall be criteria and evaluation procedures in place to protect the safety of donors during the process of cellular therapy product collection.
C6.3.1.1 The Apheresis Collection Facility shall ensure that any abnormal findings are reported to the prospective donor with documentation in the donor record of recommendations made for follow-up care.
C6.3.1.2 Allogeneic donor suitability should be evaluated by a licensed health care professional who is not the primary transplant physician or health care professional overseeing care of the recipient.
C6.3.1.3 Autologous donors shall be tested as required by applicable laws and regulations.
C6.3.2 The risks of donation shall be evaluated and documented, including:
C6.3.2.1 Possible need for central venous access.
C6.3.2.2 Mobilization therapy for collection of HPC, Apheresis.
C6.3.3 The donor should be evaluated for the risk of hemoglobinopathy prior to administration of the mobilization regimen.
C6.3.4 A pregnancy assessment shall be performed for all female donors with childbearing potential within seven (7) days preceding donor mobilization, cellular therapy product collection, or initiation of the recipient’s preparative regimen, whichever occurs earliest.
C6.3.5 Laboratory testing of all donors shall be performed by a laboratory accredited, registered, or licensed in accordance with applicable laws and regulations using one or more donor screening tests approved or cleared by the governmental authority.
C6.3.6 A donor advocate should be available to represent allogeneic donors who are minors or who are mentally incapacitated.
C6.3.7 Collection from a donor who does not meet Clinical Program collection safety criteria shall require documentation of the rationale for his/her selection by the transplant physician. Collection staff shall document review of these donor safety issues.
C6.3.8 Issues of donor health that pertain to the safety of the collection procedure shall be communicated in writing to the Apheresis Collection Facility staff. Collection staff shall document review of these issues prior to collection.
C6.3.9 There shall be a policy for follow-up of donors that includes routine management and the management of donation-associated adverse events.
C6.4 ADDITIONAL REQUIREMENTS FOR ALLOGENEIC DONORS
C6.4.1 Allogeneic donors and allogeneic recipients shall be tested for ABO group and Rh type using two independently collected samples. Discrepancies shall be resolved and documented prior to issue of the cellular therapy product.
C6.4.2 A red cell antibody screen shall be performed on allogeneic recipients.
C6.4.3 The Apheresis Collection Facility shall comply with B6.4.3 through
B6.4.4.8 when primarily responsible for donor screening for transmissible disease.
C6.4.4 The Apheresis Collection Facility shall comply with B6.4.5 through B6.4.9 when primarily responsible for infectious disease testing of HPC donors.
C6.4.5 The Apheresis Collection Facility shall comply with B6.4.10 through
B6.4.11 when primarily responsible for testing for the selection of allogeneic donors.
C6.4.6 The Apheresis Collection Facility shall ensure that allogeneic donor eligibility, as defined by applicable laws and regulations, is determined by a physician after history, exam, medical record review, and testing before the donor begins the mobilization regimen.
C6.4.7 Collection of a cellular therapy product from an ineligible allogeneic donor shall require documentation of urgent medical need that includes the rationale for the selection and documentation of the informed consent of the donor and the recipient.
C6.4.8 Allogeneic donor eligibility shall be communicated in writing to the Processing Facility.
C6.5 DONOR RECORDS
C6.5.1 There shall be a policy covering the creation, regular review, and retention of donor records.
C6.5.2 Apheresis Collection Facility donor records shall include at a minimum the following:
C6.5.2.1 Donor identification including at least name and date of birth.
C6.5.2.2 Age, gender, and medical history, and, if applicable, behavioral history.
C6.5.2.3 Consent to donate.
C6.5.2.4 Results of laboratory testing.
C6.5.2.5 Donor eligibility determination, including the name of the responsible person who made the determination and the date of the determination.
C7 CODING AND LABELING OF CELLULAR THERAPY PRODUCTS
C7.1 ISBT 128 CODING AND LABELING
C7.1.1 Cellular therapy products shall be identified according to the proper name of the product, including appropriate modifiers and attributes, as defined in ISBT 128 Standard Terminology for Blood, Cellular Therapy, and Tissue Product Descriptions.
C7.1.2 If the Apheresis Collection Facility has not fully implemented ISBT 128 technology, an implementation plan for the usage of ISBT 128 coding and labeling shall be in place.
C7.2 LABELING OPERATIONS
C7.2.1 Labeling operations shall be conducted in a manner adequate to prevent mislabeling or misidentification of cellular therapy products and product samples.
C7.2.2 The labeling operation for pre-printed labels shall include, at a minimum, the following controls:
C7.2.2.1 Labels shall be held upon receipt from the manufacturer pending review and proofing against a copy or template approved by the Apheresis Collection Facility Director or designee to ensure accuracy regarding identity, content, and conformity.
C7.2.2.2 Stocks of unused labels for different products shall be stored in a controlled manner to prevent errors.
C7.2.2.3 Stocks of obsolete labels shall be destroyed.
C7.2.3 Print-on-demand label systems shall be validated to ensure accuracy regarding identity, content, and conformity of labels to templates approved by the Apheresis Collection Facility Director or designee.
C7.2.4 A system for label version control shall be employed.
C7.2.4.1 Representative obsolete labels shall be archived for ten (10) years with inclusive dates of use or as defined by applicable laws and regulations.
C7.2.5 A system of checks in labeling procedures shall be used to prevent errors in transferring information to labels.
C7.2.5.1 Cellular therapy products that are subsequently re-packaged into new containers shall be labeled with new labels before they are detached from the original container.
C7.2.5.2 A controlled labeling procedure consistent with applicable law shall be defined and followed if container label information is transmitted electronically during a labeling process. This procedure shall include a verification step.
C7.2.6 When the label has been affixed to the container, a sufficient area of the container shall remain uncovered to permit inspection of the contents.
C7.2.7 The information entered on a container label shall be verified by at least two (2) staff members.
C7.2.8 Labeling elements required by applicable laws and regulations shall be present.
C7.2.9 All data fields on labels shall be completed.
C7.2.10 All labeling shall be clear, legible, and completed using ink that is indelible to all relevant agents.
C7.2.11 Labels affixed directly to a cellular therapy product bag shall be applied using appropriate materials as defined by the applicable regulatory authority.
C7.2.12 The label shall be validated as reliable for storage under the conditions in use.
C7.3 PRODUCT IDENTIFICATION
C7.3.1 Each cellular therapy product shall be assigned a unique numeric or alphanumeric identifier by which it will be possible to trace any cellular therapy product to its donor and to all records describing the handling and final disposition of the product.
C7.3.1.1 The cellular therapy product, concurrent plasma, and donor and product samples shall be labeled with the same identifier.
C7.3.1.2 If a single cellular therapy product is stored in more than one container, there shall be a system to identify each container.
C7.3.1.3 If cellular therapy products from the same donor are pooled, the pool identifier shall allow tracing to the original products.
C7.3.2 Apheresis Collection Facilities may designate an additional or supplementary unique numeric or alphanumeric identifier to the cellular therapy product.
C7.3.2.1 Supplementary identifiers shall not obscure the original identifier.
C7.3.2.2 The facility associated with each identifier shall be noted on the label.
C7.4 LABEL CONTENT
C7.4.1 At the end of the cellular therapy product collection, the cellular therapy product label on the primary product container and concurrent plasma container shall bear the information in the Cellular Therapy Product Labeling table in Appendix I.
C7.4.2 Each label shall bear the appropriate biohazard and warning labels as found in the Circular of Information (COI) for the Use of Cellular Therapy Products, “Table 2. Biohazard and Warning Labels on Cellular Therapy Products Collected, Processed, and/or Administered in the United States.”
C7.5 LABELING AT COMPLETION OF COLLECTION
C7.5.1 Labeling at the end of collection shall occur before the cellular therapy product bag is disconnected from the donor.
C7.6 ACCOMPANYING DOCUMENTATION AT THE END OF COLLECTION
C7.6.1 Cellular therapy products collected in or designated for use in the U.S. shall be accompanied by the elements listed in the Accompanying Documents at Distribution table in Appendix III at the time of distribution.
C7.7 ADDITIONAL DOCUMENTATION AT OR IMMEDIATELY AFTER
DISTRIBUTION
C7.7.1 For cellular therapy products distributed before completion of donor eligibility determination, there shall be documentation that donor eligibility determination was completed during or after the use of the product.
C8 PROCESS CONTROLS
C8.1 Collection of cellular therapy products shall be performed according to written procedures in the Apheresis Collection Facility’s Standard Operating Procedures Manual.
C8.2 There shall be a process for inventory control that encompasses equipment, reagents, supplies, and labels.
C8.2.1 There shall be a system to uniquely identify and track and trace all critical equipment, reagents, supplies, and labels used in the collection of cellular therapy products.
C8.2.2 Each supply and reagent used to collect cellular therapy products shall be visually examined at receipt and prior to use for damage or evidence of contamination.
C8.2.3 Supplies and reagents coming into contact with cellular therapy products during collection shall be sterile and of the appropriate grade for the intended use.
C8.3 Equipment shall be standardized and calibrated on a regularly scheduled basis as described in Standard Operating Procedures and in accordance with the manufacturer’s recommendations.
C8.4 Equipment shall conform to applicable laws and regulations, where applicable.
C8.5 There shall be written documentation of an interim assessment of donor suitability for the collection procedure performed by a qualified person immediately prior to each collection procedure.
C8.5.1 A complete blood count, including platelet count, shall be performed within 24 hours prior to each HPC collection by apheresis.
C8.5.2 There shall be peripheral blood count criteria to proceed with collection.
C8.6 Before cell collection is undertaken, there shall be a written order from a physician specifying, at a minimum, timing and goals of collection.
C8.7 If required, central venous catheters shall be placed by a licensed health care professional qualified to perform the procedure.
C8.7.1 Adequacy of line placement shall be verified by the Apheresis Collection Facility.
C8.8 Administration of mobilization agents shall be under the supervision of a licensed health care professional experienced in their administration and management of complications in persons receiving these agents.
C8.9 The Apheresis Collection Facility shall utilize a process for assessing the quality of cellular therapy products to ensure their safety, viability, and integrity and to document that products meet predetermined release specifications. Results of all such assessments shall become part of the permanent record of the product collected.
C8.9.1 Methods for collection shall include a process for controlling and monitoring the collection of cellular therapy products to ensure products meet predetermined release specifications.
C8.9.2 Methods for collection shall employ procedures validated to result in acceptable cell viability and recovery.
C8.10 Collection methods shall employ aseptic technique to ensure that cellular therapy products do not become contaminated during collection.
C8.11 Collection methods for pediatric donors shall employ appropriate age and size adjustments to the procedures.
C8.12 Cellular therapy products shall be packaged in a closed sterile transfer pack appropriate for blood or marrow products.
C8.13 Records shall be made concurrently with each step of collection of each cellular therapy product in such a way that all steps may be accurately traced.
