Principle
- Collection and processing activities should follow clearly defined procedures; they should comply with the principles of Good Manufacturing Practice in order to obtain products of the requisite quality and be in accordance with regulatory requirements.
- Collection and processing should be conducted in a manner that minimises errors and the risk of particulate and microbial contamination.
General
- Collection and processing should be performed and supervised by competent people.
- All handling of materials and products, such as receipt and quarantine, sampling, storage, labelling, collection, processing, packaging and distribution should be done in accordance with written procedures and, where necessary, recorded.
Collection
- The selection of donors and relevant screening tests including those for infectious agents should ensure that the manufactured products are suitable for their intended purpose.
- Donors should be selected according to documented procedures defining the selection criteria, infectious disease screening tests and any other relevant tests.
- A procedure should be established, implemented and maintained for obtaining medical and other required statutory information prior to donation.
- For Tissue Collections, there should be a documented procedure for defining the medical assessment requirements for live and deceased donors, including the acceptable timeframe for assessment, if not able to be done on the day of donation. For a live donor, the donor selection records, including consent and medical history, signed by the donor should be witnessed and signed by an authorised person.
- For Tissue collections, in the case of the deceased donation, the medical assessment records examined should be documented and there must be a statement of acceptability of the donor signed by a nominated authorised person. The medical assessment should be made as close as possible to collection.
- For Blood, Blood Components and Cellular Therapy Products, there should be a documented procedure for defining the medical assessment requirements including the acceptable timeframe for assessment, if not able to be done on the day of collection. The donor selection records, including informed consent, and final assessment, should be reviewed and recorded by an authorised person.
- Donor selection records, including informed consent and final assessment, should be reviewed and recorded by an authorised person to ensure the suitability of the donor.
- Where State/Federal requirements require consent for the collection of tissue or cells, the consent must be obtained. In exceptional circumstances where consent cannot be obtained at collection, the consent should be obtained before tissue or cellular therapy products can be released.
- Procedures for donation should be established, implemented and maintained.
- For Blood donations, the procedures should include requirements that donor selection interview and donor assessment should take place immediately before each donation and donor identification be confirmed before venepuncture.
- At donation, any information, which may affect product quality, should be recorded.
- The donor identification and any critical materials used should be traceable to the donation and associated records.
- Collection areas should be organised to avoid any potential errors with donor records or labels.
- The donation number or a unique identifier to the donor should be on all product and sample containers, and on donor records. This should be checked and the check recorded. Donation numbers should not be repeated, unless after a reasonable timeframe.
- Procedures for the identification labelling of donations should be established, implemented and maintained. The procedures should be designed to avoid any risk of identification error or mix-up. They should require that labels be reconciled and any discrepancy investigated.
- Collection of Cells and Tissues should be performed aseptically and carried out under controlled conditions. Equipment used should be sterile. Retrieved tissue and cellular therapy products should be packaged using sterile containers and in a manner which will minimise contamination.
- Collection documentation and records should include:
- The donor identity;
- The date, time and place of the procedure;
- The identity of the person(s) performing the collection;
- For Cellular Therapy Products; : the Cells collected, Donor and cell selection information, details of the physical examination of the donor prior to collection;
- For Tissues: the Tissue(s) collected, Donor and Tissue selection information, details of the physical examination of the donor prior to collection.
- Confidentiality of the donor should be maintained.
- If applicable, documented procedures for the transport of donations should be established, implemented and maintained. The procedures should ensure that the integrity of donations is protected and traceability is maintained.
Processing
- Tissue and cellular therapy products should be processed in an environment and manner, which will prevent contact or cross contamination with tissues or cellular therapy products from other donors.
- Before any processing operation is started, steps should be taken to ensure that the work area and equipment are clean and free from any starting materials, blood or blood component, tissue or cellular therapy product residues or documents not required for the current operation. Records should be maintained.
- There should be documentation, which defines the material, procedures and controls used in the processing of product.
- Records of processing should provide traceability and, as applicable, include:
- the date, time, venue, unique identifying donation number(s);
- the identity of the person(s) performing and authorising critical steps;
- the in-process quality control tests performed;
- the equipment used;
- all products prepared from each donation.
- Where a process is applied to Tissue or Cellular Therapy Products from a number of donors at the same time (e.g. bioburden reduction) a unique batch number should be included in the records.
- Process records should be reviewed and the review recorded.
- There should be a system in place to maintain and control work in progress Tissue or Cellular Therapy Products, including any transportation required.
- There should be procedures in place for all specific processing steps such as: antibiotic treatment, enzymatic digestion, the use of cell selection devices, and addition of additives or growth factors.
Treatment by radiation
- The exposure time, load configuration and radiation source, should be set to ensure that all products receive the specified minimum dose, with no part receiving more than the maximum specified dose.
- Materials handling procedures should prevent mix-up between irradiated and non-irradiated materials. Radiation-sensitive colour indicators should also be used to differentiate between products, which have been subjected to irradiation, and those, which have not.
Freeze drying
- Freeze drying records should be maintained including time, temperature and vacuum pressure at each step in the cycle.
Cryopreservation
- Cryopreservation records should be maintained includes the time and temperature of the process.
Storage and despatch
- Storage and despatch processes should take place according to documented procedures to assure product quality during the storage period and to avoid mix-ups of products.
- There should be a system in place to maintain and control the storage of products during their shelf life, including any transportation that may be required.
Validation
- The key elements of a validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document. Validation studies should reinforce Good Manufacturing Practice and be conducted in accordance with defined procedures. Results and conclusions should be recorded.
- The manufacturer should identify what validation work is required to demonstrate control of the manufacturing process. A risk assessment approach should be used to determine the scope and the extent of the validation.
- Significant changes to the manufacturing process, including any change in equipment or materials, which may affect product quality and/or reproducibility of the process, should be validated.
- When any changes to the manufacturing process are adopted, steps should be taken to demonstrate its suitability for routine processing. The defined process, using the materials and equipment specified, should be shown to consistently yield a product of the required quality.
Process validation
- Process validation should normally be completed prior to the release of the therapeutic product (prospective validation). In exceptional circumstances, where this is not possible, it may be necessary to validate processes during routine processing (concurrent validation). Processes in use for some time should also be validated (retrospective validation).
- Facilities, systems and equipment to be used should be qualified and quality control testing methods should be validated.
- Facilities, systems equipment and processes should be periodically evaluated to verify that they are still operating in a valid manner.