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, 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 in vitro 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.
