D7 CODING AND LABELING OF CELLULAR THERAPY PRODUCTS
D7.1 ISBT 128 CODING AND LABELING
D7.1.1 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.
D7.1.2 If the Processing Facility has not fully implemented ISBT 128 technology, an implementation plan for the usage of ISBT 128 coding and labeling shall be in place.
D7.2 LABELING OPERATIONS
D7.2.1 Labeling operations shall be conducted in a manner adequate to prevent mislabeling or misidentification of cellular therapy products and product samples.
D7.2.2 The labeling operation for pre-printed labels shall include, at a minimum, the following controls:
D7.2.2.1 Labels shall be held upon receipt from the manufacturer pending review and proofing against a copy or template approved by the Processing Facility Director or designee to ensure accuracy regarding identity, content, and conformity.
D7.2.2.2 Stocks of unused labels for different cellular therapy products shall be stored in a controlled manner to prevent errors.
D7.2.2.3 Stocks of obsolete labels shall be destroyed.
D7.2.3 Print-on-demand label systems shall be validated to ensure accuracy regarding identity, content, and conformity of labels to templates approved by the Processing Facility Director or designee.
D7.2.4 A system for label version control shall be employed.
D7.2.4.1 Representative obsolete labels shall be archived minimally for ten (10) years with inclusive dates of use or as defined by applicable laws and regulations.
D7.2.5 A system of checks in labeling procedures shall be used to prevent errors in transferring information to labels.
D7.2.5.1 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.
D7.2.5.2 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.
D7.2.6 When the label has been affixed to the container, a sufficient area of the container shall remain uncovered to permit inspection of the contents.
D7.2.7 The information entered on a container label shall be verified by at least two (2) staff members prior to distribution of the cellular therapy product.
D7.2.8 Labeling elements required by applicable laws and regulations shall be present.
D7.2.9 All data fields on labels shall be completed.
D7.2.10 All labeling shall be clear, legible, and completed using ink that is indelible to all relevant agents.
D7.2.11 Labels affixed directly to a cellular therapy product bag shall be applied using appropriate materials as defined by the applicable regulatory authority.
D7.2.12 The label shall be validated as reliable for storage under the conditions in use.
D7.3 PRODUCT IDENTIFICATION
D7.3.1 Each cellular therapy product shall be assigned a unique numeric or alphanumeric identifier by which it will be possible to trace any product to its donor and to all records describing the handling and final disposition of the product.
D7.3.1.1 The cellular therapy product, concurrent plasma, and donor and product samples shall be labeled with the same identifier.
D7.3.1.2 If a single cellular therapy product is stored in more than one container, there shall be a system to identify each container.
D7.3.1.3 If cellular therapy products from the same donor are pooled, the pool identifier shall allow tracing to the original products.
D7.3.2 The Processing Facility may designate an additional or supplementary unique numeric or alphanumeric identifier to the cellular therapy product.
D7.3.2.1 Supplementary identifiers shall not obscure the original identifier.
D7.3.2.2 The facility associated with each identifier shall be noted on the label.
D7.4 LABEL CONTENT
D7.4.1 Each label shall bear the information in the Cellular Therapy Product Labeling table in Appendix I.
D7.4.2 Each label shall bear the appropriate biohazard and warning labels as found in the Circular of Information 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.”
D7.5 PARTIAL LABEL
D7.5.1 If the cellular therapy product container is capable of bearing only a partial label, the container shall have affixed, at a minimum, the unique numeric or alphanumeric identifier of the product, the proper name of the product, the appropriate product modifiers, and, if known, the name and identifier of the intended recipient.
D7.5.2 Minimally, the information required in D7.5.1 shall be present on the cellular therapy product during all stages of processing.
D7.5.3 Any container bearing a partial label shall be accompanied by the information required by the Cellular Therapy Product Labeling table in Appendix I. Such information shall be attached securely to the cellular therapy product on a tie tag or enclosed in a sealed package to accompany the product.
D7.6 LABELING AT COMPLETION OF PROCESSING
D7.6.1 At the end of processing, the label on the cellular therapy product container shall bear the information in the Cellular Therapy Product Labeling table in Appendix I.
D7.7 LABELING AT DISTRIBUTION
D7.7.1 At the time of distribution, the label on the cellular therapy product container shall bear the information in the Cellular Therapy Product Labeling table in Appendix I.
D7.7.2 The name and address of the facility that determines that the cellular therapy product meets release criteria and the name and address of the facility that makes the product available for distribution shall either appear on the product label or accompany the product at distribution.
D7.8 ACCOMPANYING DOCUMENTATION AT DISTRIBUTION
D7.8.1 Products collected in or designated for use in the U.S. shall have the elements in the Accompanying Documents at Distribution table in Appendix III accompany the cellular therapy product when it leaves the Processing Facility.
D7.9 DOCUMENTATION IMMEDIATELY AFTER DISTRIBUTION
D7.9.1 For cellular therapy products distributed before completion of donor eligibility determination, there shall be documentation that donor eligibility
determination was completed during or after distribution of the cellular therapy product and that the physician using the product was informed of the results of that determination.
D8 DISTRIBUTION
D8.1 PROCESSING, TRACKING, AND RELEASE CRITERIA
D8.1.1 The processing, collection, and transport or shipping records for each cellular therapy product shall be reviewed by the Processing Facility Director or designee for compliance with Standard Operating Procedures and applicable laws and regulations prior to product release or distribution.
D8.1.1.1 Records shall demonstrate track ability from the donor to the recipient and trace ability from the recipient to the donor.
D8.1.2 Each cellular therapy product shall meet pre-determined release criteria prior to distribution from the Processing Facility. The release criteria shall include donor eligibility determination for allogeneic products.
D8.1.2.1 The Processing Facility Director or designee shall give specific authorization for release when the cellular therapy product does not meet technical release criteria.
D8.1.2.2 The Processing Facility Medical Director or designee shall give specific authorization for release when the cellular therapy product does not meet clinically relevant release criteria.
D8.1.2.3 Documentation of agreement of the Processing Facility Medical Director or designee and the recipient’s physician consent to use any non-conforming product shall be retained in the processing record.
D8.1.3 Each cellular therapy product issued for administration shall be visually inspected by two (2) trained personnel immediately before release to verify the integrity of the product container and appropriate labeling.
D8.1.3.1 A cellular therapy product shall not be released when the container is compromised and/or recipient or donor information is not verified unless the Processing Facility Director or designee gives specific authorization for the product’s release.
D8.2 DISTRIBUTION RECORDS
D8.2.1 The cellular therapy product processing records shall contain a written or printed record of product distribution including, at a minimum:
D8.2.1.1 The distribution date and time.
D8.2.1.2 Unique identifier of the intended recipient.
D8.2.1.3 The proper product name and identifier.
D8.2.1.4 Documentation of donor eligibility determination.
D8.2.1.5 Identification of the facility that distributed the product.
D8.2.2 The distribution record shall include documentation of:
D8.2.2.1 The identity of the individual who accepted the cellular therapy product.
D8.2.2.2 The date and time of receipt.
D8.3 CIRCULAR OF INFORMATION
D8.3.1 For each type of cellular therapy product, the Processing Facility shall maintain and distribute or make a document available to clinical staff containing the following as appropriate:
D8.3.1.1 The use of the cellular therapy product, indications, contraindications, side effects and hazards, dosage, and administration recommendations.
D8.3.1.2 Instructions for handling the cellular therapy product to minimize the risk of contamination or cross-contamination.
D8.3.1.3 Appropriate warnings related to the prevention of the transmission or spread of communicable diseases.
D8.4 RETURN OF CELLULAR THERAPY PRODUCTS FROM ISSUE
D8.4.1 Cellular therapy products accepted for return shall meet the following criteria:
D8.4.1.1 The integrity of the primary container has not been compromised.
D8.4.1.2 The cellular therapy product has been maintained, subsequent to issue, at the specified temperature range during storage and shipping or transportation.
D8.4.2 If the criteria in Standards D8.4.1.1 and D8.4.1.2 have not been met, the Processing Facility shall not return the product to inventory unless the Processing Facility Director or designee gives specific authorization.
D8.4.3 The Processing Facility Director or designee shall consult with the recipient’s physician regarding reissue or disposal of the returned product.
D8.4.4 Documentation of the events requiring return, the results of inspection upon return, and subsequent action taken to ensure product safety and viability shall be maintained in the Processing Facility records.
D9 STORAGE
D9.1 Processing Facilities shall control storage areas to prevent mix-ups, deterioration, contamination, cross-contamination, and improper distribution of cellular therapy products.
D9.2 STORAGE DURATION
D9.2.1 Processing Facilities, in consultation with the Clinical Program, shall establish policies for the duration and conditions of storage and indications for disposal.
D9.2.1.1 Patients, donors, and associated Clinical Programs should be informed about these policies before the cellular therapy product collection.
D9.2.2 Processing Facilities processing, storing, and/or releasing cellular therapy products for administration shall assign an expiration date and time, as appropriate, for non-cryopreserved products and for products thawed after cryopreservation.
D9.3 TEMPERATURE
D9.3.1 Storage temperatures shall be defined in Standard Operating Procedures.
D9.3.2 Noncryopreserved cellular therapy products shall be maintained within a specific temperature range to maintain viability and function, to inhibit infectious agents, and for a period of time not to exceed that specified in Standard Operating Procedures.
D9.3.3 Cryopreserved cellular therapy products shall be stored within a temperature range, as defined in Standard Operating Procedures, that is appropriate for the product and cryoprotectant solution used.
D9.4 PRODUCT SAFETY
D9.4.1 Materials that may adversely affect cellular therapy products shall not be stored in the same refrigerators or freezers as the cellular therapy products.
D9.4.2 For cellular therapy products immersed in liquid nitrogen, procedures to minimize the risk of cross-contamination of products shall be employed.
D9.4.3 Processing Facilities storing cellular therapy products shall quarantine each product until completion of the donor eligibility determination as required by applicable laws and regulations.
D9.4.3.1 All cellular therapy products with positive infectious disease test results for relevant communicable disease agents and/or positive microbial cultures shall be quarantined.
D9.4.3.2 Processes for storing cellular therapy products in quarantine shall be defined in Standard Operating Procedures.
D9.4.3.3 Quarantined cellular therapy products shall be easily distinguishable and stored in a manner that minimizes the risks of cross-contamination and inappropriate distribution.
D9.5 MONITORING
D9.5.1 Refrigerators and freezers used for storage where cellular therapy products are not fully immersed in liquid nitrogen shall have a system to monitor the temperature continuously and to record the temperature at least every four (4) hours.
D9.5.2 There shall be a mechanism to ensure that levels of liquid nitrogen in liquid nitrogen freezers are consistently maintained to assure that cellular therapy products remain within the specified temperature range.
D9.6 ALARM SYSTEMS
D9.6.1 Storage devices for cellular therapy products or reagents for cellular therapy product processing shall have alarm systems that are continuously active.
D9.6.2 Alarm systems shall have audible signals or other effective notification methods.
D9.6.3 Alarm systems shall be checked periodically for function.
D9.6.4 If trained personnel are not always present in the immediate area of the storage device, a system shall be in place that alerts responsible personnel of alarm conditions on a 24-hour basis.
D9.6.5 Alarms shall be set to activate at a temperature or level of liquid nitrogen that will allow time to salvage products.
D9.6.6 Written instructions to be followed if the storage device fails shall be displayed in the immediate area of the storage device and at each remote alarm location.
D9.6.6.1 Instructions shall include a procedure for notifying processing personnel.
D9.6.6.2 Instructions shall outline procedures to follow to ensure that cellular therapy products are maintained at safe temperatures and the process for documentation of any corrective actions in order to maintain integrity of the products.
D9.6.7 Additional storage devices of appropriate temperature shall be available for cellular therapy product storage if the primary storage device fails.
D9.7 SECURITY
D9.7.1 The storage device shall be located in a secure area and accessible only to authorized personnel.
D9.8 INVENTORY CONTROL
D9.8.1 The Processing Facility shall use an inventory control system to document the availability and identity of critical reagents and supplies.
This shall include:
D9.8.1.1 A system to uniquely identify and track all critical reagents and supplies used to manufacture cellular therapy products.
D9.8.1.2 A system to identify each cellular therapy product for which each critical reagent or supply was used.
D9.8.1.3 A system to maintain adequate stocks of reagents and supplies for the procedures to be performed.
D9.8.2 The Processing Facility shall use an inventory control system to identify the location of each cellular therapy product and associated sample aliquots. The inventory control system records shall include:
D9.8.2.1 Cellular therapy product proper name or specimen name.
D9.8.2.2 Cellular therapy product unique identifier.
D9.8.2.3 Recipient name or unique identifier.
D9.8.2.4 Storage device identifier.
D9.8.2.5 Location within the storage device.
D10 TRANSPORTATION, SHIPPING, AND RECEIPT
D10.1 Procedures shall be established and maintained for transportation, shipping, and receipt of cellular therapy products.
D10.2 Procedures for transportation and shipping of cellular therapy products shall be designed to protect the integrity of the product and the health and safety of individuals in the immediate area and shall follow the applicable laws and regulations.
D10.2.1 The primary product container for non-frozen cellular therapy products shall be placed in a secondary container and sealed to prevent leakage.
D10.3 Cellular therapy products that require a temperature-controlled environment and that are transported or shipped over an extended period of time shall be
transported or shipped in a container validated to maintain the appropriate temperature range.
D10.3.1 During transportation or shipping, the cellular therapy product temperature shall be maintained at the transport or shipping temperature specified by the receiving facility.
D10.4 Cellular therapy products that are shipped to another facility or transported on public roads shall be packaged in an outer container.
D10.4.1 Conditions shall be established and maintained to preserve the integrity and safety of cellular therapy products during transport or shipping.
D10.4.2 The outer container shall conform to the applicable regulations regarding the mode of transportation or shipping.
D10.4.3 The outer container shall be made of material adequate to withstand leakage of contents, shocks, pressure changes, and other conditions incident to ordinary handling during transport or shipping.
D10.4.3.1 The temperature of shipping containers bearing cryopreserved cellular therapy products shall be continuously monitored during shipping.
D10.4.3.2 The shipping facility shall maintain a record of the temperature over the period of travel.
D10.4.4 The outer container shall be labeled as defined in the Cellular Therapy Product Labels for Shipping and Transport on Public Roads table in Appendix II.
D10.4.5 There shall also be a document inside the outer container that includes all the information required on the outer container, in conformity with the Cellular Therapy Product Labels for Shipping and Transport on Public Roads table in Appendix II.
D10.4.6 The outer container shall be labeled in accordance with applicable laws and regulations regarding the cryogenic material used and the transport or shipment of biological materials.
D10.5 METHOD OF TRANSPORTATION AND SHIPPING
D10.5.1 The transit time shall be within time limits determined by the receiving and/or distributing facility to maintain cellular therapy product safety.
D10.5.2 If the intended recipient has received high-dose therapy, the cellular therapy product shall be transported by a qualified courier.
D10.5.3 There shall be plans for alternative means of transport or shipping in an emergency.
D10.5.4 The cellular therapy products should not be passed through X-Ray irradiation devices designed to detect metal objects. If inspection is necessary, the contents of the container should be inspected manually.
D10.6 RECEIPT
D10.6.1 Procedures shall be established and maintained for acceptance, rejection, and quarantine of cellular therapy products.
D10.6.2 The receipt of each cellular therapy product shall include inspection to verify the integrity of the product container, the appearance of the product, and appropriate labeling, and to evaluate for evidence of microbial contamination.
D10.6.3 There shall be procedures to verify that the cellular therapy product was appropriately transported or shipped.
D10.6.3.1 The receiving facility shall document the temperature of the outer container upon arrival.
D10.6.3.2 For cryopreserved cellular therapy products, receiving facility records shall include documentation of the outer container temperature during shipping.
D10.6.4 The receiving facility shall have readily available access to a summary of documents used to determine allogeneic donor suitability and eligibility.
D10.6.5 There shall be procedures to maintain cellular therapy products in quarantine until they have been determined to meet criteria for release from quarantine.
D10.7 TRANSPORTATION AND SHIPPING RECORDS
D10.7.1 Transportation and shipping records shall permit tracing of the cellular therapy product from one facility to another.
D10.7.2 Transportation and shipping records shall include:
D10.7.2.1 Date and time cellular therapy product was distributed.
D10.7.2.2 Date and time cellular therapy product was received.
D10.7.2.3 Identity of the transporting or shipping facility.
D10.7.2.4 Identity of the receiving facility.
D10.7.2.5 Identity of personnel responsible for cellular therapy product transportation or shipping and of personnel responsible for receiving the product.
D10.7.2.6 Identity of the courier.
D10.7.2.7 Documentation of any delay or problems incurred during transportation or shipping.
D11 DISPOSAL
D11.1 Disposal of cellular therapy products shall include the following requirements:
D11.1.1 A pre-collection written agreement between the storage facility and the designated recipient or the donor, as appropriate, defining the length of storage and the circumstances for disposal of cellular therapy products.
D11.1.2 The option to transfer the cellular therapy product to another facility if the designated recipient is still alive after the agreed upon storage interval.
D11.1.3 Documentation of designated recipient’s death or no further need for the cellular therapy product before any product is discarded.
D11.1.4 Approval by the Processing Facility Medical Director or the recipient’s physician for cellular therapy product discard or other disposition, and method of disposal.
D11.1.5 A method of disposal and decontamination that meets applicable laws and regulations for disposal of biohazardous materials and/or medical waste.
D11.2 If there is no pre-existing agreement describing conditions for cellular therapy product storage and/or discard or if the patient is lost to follow-up, the storage facility shall:
D11.2.1 Communicate with the designated recipient’s physician about continuing need for storage of the cellular therapy product.
D11.2.2 Make a documented effort to notify the donor or designated recipient about product disposition, including disposal or transfer.
D11.3 The records for discarded or transferred cellular therapy products shall indicate the product was discarded or transferred, date of discard or transfer, disposition, and method of disposal or transfer.
D12 RECORDS
D12.1 GENERAL REQUIREMENTS
D12.1.1 A records management system shall be established and maintained to facilitate the review of records pertaining to a particular cellular therapy product prior to distribution and for follow-up evaluation or investigation.
D12.1.1.1 The records management system shall facilitate tracking of the cellular therapy product from the donor to the recipient or final disposition and tracing from the recipient or final disposition to the donor.
D12.1.1.2 For cellular therapy products that are to be distributed for use at another institution, the receiving institution shall be informed of the tracking system and requirement for tracking the product in writing or electronic format at or before the time of product distribution.
D12.1.2 Records shall be maintained in such a way as to ensure their integrity and preservation.
D12.1.2.1 If records are maintained in more than one location, there shall be a system to ensure prompt identification, location, and retrieval of all records.
D12.1.2.2 Records shall be accurate, legible, and indelible.
D12.1.3 All records and communications between the collection, processing, and transplant facilities, and their recipients and donors, shall be regarded as privileged and confidential.
D12.1.3.1 Safeguards to assure this confidentiality shall be established and followed in compliance with applicable laws and regulations.
D12.1.4 Records required for donor eligibility determination shall be in English or translated into English when crossing international borders.
D12.1.5 Employee records shall be maintained in a confidential manner as required by applicable laws and regulations.
D12.1.6 Records shall be maintained in one or more forms that are retrievable.
D12.1.6.1 Equipment to make the records available and legible shall be readily accessible.
D12.2 ELECTRONIC RECORDS
D12.2.1 The Processing Facility shall establish and maintain a current listing of all critical electronic record systems. Critical electronic record systems shall include at a minimum systems under the control of the Processing Facility that are used:
D12.2.1.1 In lieu of paper.
D12.2.1.2 To make decisions.
D12.2.1.3 To perform calculations.
D12.2.1.4 To create and/or store information used in critical procedures.
D12.2.2 For all critical electronic record systems, there shall be policies, procedures, and system elements to ensure the accuracy, integrity, identity, and confidentiality of all records.
D12.2.2.1 There shall be a means by which access to electronic records is limited to authorized individuals.
D12.2.2.2 There shall be protection of the records to enable their accurate and ready retrieval throughout the period of record retention.
D12.2.2.3 All critical electronic record systems shall ensure that all donor, cellular therapy product, and recipient identifiers are unique.
D12.2.3 For all critical electronic record systems, there shall be an alternative system for all electronic records that ensures continuous operation of the Processing Facility in the event that critical electronic record systems are not available. The alternative system shall be validated and Processing Facility staff shall be trained in its use.
D12.2.4 For all critical electronic record systems, there shall be written procedures for record entry, verification, and revision.
D12.2.4.1 A method shall be established or the system shall provide for review of data before final acceptance.
D12.2.4.2 A method shall be established or the system shall provide for the unambiguous identification of the individual responsible for each record entry.
D12.2.5 For all critical electronic record systems, there shall be the ability to generate true copies of the records in both human readable and electronic format suitable for inspection and review.
D12.2.6 For all critical electronic record systems, there shall be validated procedures for and documentation of:
D12.2.6.1 Systems development.
D12.2.6.2 Numerical designation of system versions, if applicable.
D12.2.6.3 Prospective validation of system, including hardware, software, and databases.
D12.2.6.4 Installation of the system.
D12.2.6.5 Training and continued competency of personnel in systems use.
D12.2.6.6 Monitoring of data integrity.
D12.2.6.7 Back-up of the electronic records system on a regular schedule.
D12.2.6.8 System maintenance and operations.
D12.2.7 All system modifications shall be authorized, documented, and validated prior to implementation.
D12.3 RECORDS TO BE MAINTAINED
D12.3.1 Records to allow tracing of cellular therapy products shall be maintained for a minimum of ten (10) years after final distribution of the product, or as required by applicable laws and regulations. These records shall include collection and processing facility identity, unique numeric or alphanumeric identifier, collection date and time, product identity, and donor and recipient information as found on the original container.
D12.3.2 Processing Facility records related to quality control, personnel training or competency, facility maintenance, facility management, or other general facility issues shall be retained for a minimum of ten (10) years by the Processing Facility, or longer in accordance with applicable laws or regulations, or with a defined program or institution policy, unless otherwise specified in these Standards.
D12.3.2.1 Facility maintenance records pertaining to facility cleaning and sanitation shall be retained for at least three (3) years. All other facility maintenance records shall be retained as in D12.3.2.
D12.3.3 All records pertaining to the processing, testing, storage, or distribution of cellular therapy products shall be maintained for a minimum of ten
(10) years after the date of administration, or if the date of administration is not known, then a minimum of ten (10) years after the date of the cellular therapy product’s distribution, disposition, or expiration, or the creation of the cellular therapy product record, whichever is most recent, or according to applicable laws and regulations or institutional policy, whichever requires the longest maintenance period. The following records shall be maintained:
D12.3.3.1 Processing records.
D12.3.3.2 Compatibility test records.
D12.3.3.3 Cryopreservation records.
D12.3.3.4 Distribution records.
D12.3.3.5 Records of errors, accidents, adverse events, adverse reactions, and complaints.
D12.3.3.6 All quality management records.
D12.4 RECORDS IN CASE OF DIVIDED RESPONSIBILITY
D12.4.1 If two (2) or more facilities participate in the collection, processing, or distribution of the cellular therapy product, the records of the Processing Facility shall show plainly the extent of its responsibility.
D12.4.2 The Processing Facility shall maintain a listing of the names, addresses, and responsibilities of other facilities that perform manufacturing steps on a cellular therapy product.
D12.4.3 There shall be a system to allow the Processing Facility access to information that tracks and traces all manufacturing steps performed by other facilities. This tracking and tracing system shall comply with D4.11.
D12.4.4 The Processing Facility shall furnish to the facility of final disposition a copy of all records relating to the collection, processing, and storage procedures performed in so far as they concern the safety, purity, or potency of the cellular therapy product involved.
Source:
FACT Accreditation Office
University of Nebraska Medical Center
986065 Nebraska Medical Center
Omaha, NE 68198-6065
Phone: (402) 559-1950
Fax: (402) 559-1951
E-mail: fact@unmc.edu
Website: www.factwebsite.org
