Approval process for allogeneic undirected cryopreserved HSC transplants - regulatory and procedural challenges

Background

Hematopoietic stem cell transplants are able to give patients a second chance of life. A significantly reduced time-to-transplant, an improved possibility of transplantation coordination and previously known product specifications of the selected transplant - these are the advantages of an inventory of undirected cryopreserved PBSC. "Allogeneic cryoPBSC, DKMS-1" was approved in April 2023 by the Paul Ehrlich Institute (PEI)as the world's first allogeneic undirected cryopreserved PBSC product .

Methods

For approval project, structural and procedural precautions were carried out. A GMP clean room unit has been built and qualified. Appropriate production and quality control processes had to be validated. DKMS SCB applied for extension of the manufacturing authorization. . A registration dossier was created for the PEI including relevant details on production, quality control methods, end product specifications, quality and shelf life data as well as a clinical and an analytical expert report. Premises and processes were inspected by the Saxony State Directorate. Moreover, collection centers that provide the undirected apheresis product as starting material also require a manufacturing license and an approval.

Results

In May 2019, the first scientific advice with the PEI for the approval of "Allogeneic cryoPBSC, DKMS-1" took place. Regulatory, structural and procedural preparations were required in preparation of the acceptance inspection by the Saxony State Directorate in November 2020. 19 months have passed between inspection to manufacturing authorization.,PEI requested rectification and additional information, in a majority focused on donor ethics and end product specification. 14 months have passed from submission of the approval dossier to the final approval. In April 2023, manufacturing authorization was given to the DKMS Collection Center.

Donor selection criteria has to be documented and assessed for 4 years after approval using real life data.

Conclusion

An approval process is time-consuming - for the applicant and also for the responsible authorities. Active communication between both parties and the early involvement of the authorities minimizes effort, misunderstanding, and simplifies the approval process. In case of "Allogeneic cryoPBSC, DKMS-1", the world's first allogeneic undirected cryopreserved PBSC product, process from scientific advice to the final approval took 4 years.

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