Cell and gene therapy products represent a varied group of cutting edge biotherapeutics. The novelty and complexity of these products demand a regulatory risk-based approach to define a sound development plan, often intended to target multiple market areas simultaneously. While de-risking plans may vary between cell and gene therapies, creating an early regulatory strategy is key to avoid unnecessary delays in clinical development.


How do you prepare a regulatory roadmap with a combined EU/US regulatory strategy to manage risks and uncertainties linked to these scientifically advanced products? In her paper, A Regulatory Risk-Based Approach to ATMP/CGT Development: Integrating Scientific Challenges with Current Regulatory Expectations, Laura Inés Salazar-Fontana, advisory board member at NDA, concludes that it is highly recommended to:

  • Discuss with the regulators the criteria for cell source characterisation since expectations may vary between FDA and EMA.
  • Provide a well validated invitro potency assay, fit for purpose early in product development as it will ensure proper product activity, help with dose selection extrapolation from non-clinical studies into FIH and support the comparability when moving from /non-/clinical batch production to commercial sale.
  • Conduct major manufacturing changes before initiating your pivotal study since it may not be feasible to gain additional clinical evidence to prove comparable safety and efficacy of the new material.
  • Use an animal model that reproduces the genetic defect aimed to be corrected by the product to avoid misinterpretation of toxicology signals.
  • When no suitable non-clinical animal model of the disease is available, provide information about proof-of-concept study results obtained in a specific in vivo model of the condition as well as supportive preliminary clinical data obtained in patients affected by the condition.
  • Request scientific advice from INTERACT, pre-IND meeting, from national competent agencies (NCA) or through the centralised Innovation Task Force (ITF) initiative of the EMA.
  • For advanced programs such as End-Of-Phase2 and/ or before finalising the design of pivotal clinical studies, seek joint advice from EMA and FDA. Use a common core document and adapt according to specific regional regulatory guidelines.
  • Incorporate the advice received from regulatory authorities into the product development plan to reduce regulatory risks and ensure completeness of the dossier when submitting your IND or MAA.

To read the full article Published in the May 13th, 2022 edition of Frontiers in Medicine by Laura I. Salazar Fontana, PhD, LAIZ Regulatory Science Consulting principal and member of NDA Advisory Board.

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The Author

Laura Inés Salazar-Fontana,  

Advisory board member

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