Fig. 3: ATMP manufacturing chain and challenges.

The chain starts with the cell-therapy team providing direct patient care. After apheresis or biopsy collection at the cell-therapy hospital, the material is anonymised, and the relevant setting is required to maintain a chain-of-custody tracking. The governance and administration team oversee the cell-therapy programme, the development and management of standard operating procedures, the outcomes of auditing processes as well as assess resource allocation and business planning. The biopsy sample is processed and transported to the manufacturing facility with a system to ensure that the integrity and chain-of-custody of the initial cellular material are maintained. At the manufacturing facility (centralised or decentralised), manufacturing specialists in GMP procedures with expertise in the standardisation of cell-therapy protocols are needed. Clean room requirements are determined by the use of open versus closed systems. A cell-product storage facility along with electronic database infrastructure for health record documentation and quality reporting preparation of manufactured products with a chain-of-custody are required. Transport of the cell product back to the hospital requires temperature and storage controls to maintain viability. In the hospital/organisation, a financial service dealing with single-case insurance agreements and institutional payer relations is required. A legal and compliance team overseeing the manufacturer contractual agreements, the interfaces with commercial manufacturers, as well as regulatory assessment for potential international trials, is also required. Similarly, staff education to provide proper clinical training and scientific and regulatory competencies (cell-therapy fellowships) are required.