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Mining scientific advice reports on cell-based products; insight in the non-clinical development program.
  • +3
  • Tineke van den Hoorn,
  • Tahira Nakchedi,
  • Charlotte de Wolf,
  • Marjon Pasmooij,
  • Jan Willem van der Laan,
  • Carla Herberts
Tineke van den Hoorn
Medicines Evaluation Board
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Tahira Nakchedi
Author Profile
Charlotte de Wolf
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Marjon Pasmooij
Author Profile
Jan Willem van der Laan
Medicines Evaluation Board
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Carla Herberts
Medicines Evaluation Board
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Abstract

Aims The field of cell-based therapies for human diseases is currently evolving from promising treatment options to established therapeutic concepts. The design of the non-clinical development program for cell-based products, intended to provide a rationale for treatment and to gain insight into the safety profile, is challenging because of limitations caused by species-specificity. The elements of the non-clinical package for cell-based products were evaluated using advice reports from the European Medicines Agency database from 2013-2018 to identify the approach followed for non-clinical development of these products. Methods The purpose of the in vivo studies was designated to be (a combination of) pharmacology/proof-of-concept, safety, biodistribution and/or tumourigenicity. For biodistribution and tumourigenicity also the need for, type and design of in vitro and in vivo studies were recorded. Results In vivo studies for cell-based therapies were primarily aimed at proof-of-concept (75/86), followed by addressing safety (64/86), biodistribution (49/86) or tumourigenicity (46/86). No animal studies were performed or proposed by sponsors or regulators for six (out of 86) products, which contained cell types that have been studied in humans for a relatively long time. For one-third of the products in vivo biodistribution and/or tumourigenicity studies were not considered necessary. In vivo tumourigenicity studies were regarded of limited value. Conclusions Compared to more conventional medicinal products, the non-clinical development program for cell-based products was more tailored and focussing on proof-of-concept. For tumourigenicity an in vitro approach may suffice. Total omission of in vivo studies appears to be possible for products with sufficient clinical experience.

Peer review status:Published

14 May 2020Submitted to British Journal of Clinical Pharmacology
15 May 2020Submission Checks Completed
15 May 2020Assigned to Editor
19 May 2020Reviewer(s) Assigned
15 Jun 2020Review(s) Completed, Editorial Evaluation Pending
18 Jun 2020Editorial Decision: Revise Minor
03 Jul 20201st Revision Received
06 Jul 2020Submission Checks Completed
06 Jul 2020Assigned to Editor
06 Jul 2020Review(s) Completed, Editorial Evaluation Pending
12 Jul 2020Editorial Decision: Revise Minor
21 Jul 20202nd Revision Received
22 Jul 2020Submission Checks Completed
22 Jul 2020Assigned to Editor
22 Jul 2020Review(s) Completed, Editorial Evaluation Pending
29 Jul 2020Editorial Decision: Accept
13 Aug 2020Published in British Journal of Clinical Pharmacology. 10.1111/bcp.14515