Relevant notes from the GAiT QC Workshop:
Prospective cell line development versus “rederivation” for GMP products
Rederivation of an iPSC line involves taking a research-grade iPSC line and, after processing it properly, placing in a clinical-grade bank. This process requires gathering information retrospectively and has the advantage of not requiring a large outlay at the beginning of the derivation process. While this approach is possible, it is not recommended as retrospective collection of information is difficult. The original hESC lines, for example, were never derived with the intention of being used in clinical trials but primarily due to the limited access to IVF embryos, and the wide use of the lines to develop manufacturing processes, the H1 hESC line was subsequently rederived and used in part of Phase II Astellas Pharma’s RPE trial, similarly the rederived H9 hESC line was used to generate dopamine neurons for BlueRock Therapeutics’ Parkinson’s trial for Parkinson’s disease. However, acquiring FDA approval, developing time frames, and generating a VOM (validation of manufacturing) are all more difficult in retrospect. It is preferable to collect information prospectively as the line is generated.
It is also imperative to know and capture all the data regulators require to use the lines for cell therapeutics development. Validating the starting material is difficult, after which it is imported and processed into GMP facility. Prospective gathering of relevant information is recommended.
Additionally, reconsenting of the donor material may be required. While ISSCR have a program for assisting in the universal consent, in practice having a common consent form is very difficult as specific uses of the lines must be detailed in advance. Early development of ECTD, showing traceability and completing the donation process are all best done prospectively.
A major source of waste would be to initiate ‘GMP’ production of iPSCs from donor cells that will ultimately fail to meet all the regulatory compliance demands for a potential cell-therapeutic. Mandatory information for donation, procurement, and testing data of donor cells is required. Where parties considering the development of clinical-grade iPSC for the GAiT haplobank system, two areas are in need of particular attention: donor consent for the cells and tissues donated and the sharing of a patient’s genetic data.
Consenting to give cells or tissue for research purposes differs from consent to cells or tissue for the development of cell therapeutics or transplantation however, and this difference should not be overlooked (Lo and Parham 2009). Generic donor consent forms for tissue deposition in clinical registries do not consider reprogramming such cells into iPSCs, and their subsequent expansion, differentiation, and use in developing a therapeutic product. Data yielded from testing donor material can have medical consequences for the patient, and there is an ethical requirement to share such information once it has been identified. This can lead to a delay to further progress the cells in the iPSC derivation process.