The validation processes for general biologics and small molecule drugs are well established and there are many guidelines from regulatory agencies to provide information and advice. However, much of this information is unsuitable for cell and gene therapies (CGT) and does not consider their unique characteristics.
This is why BioPhorum has published Cell and gene therapy validation challenges. In addition to highlighting the importance of considering the unique aspects of cell and gene therapy validation, the article offers insight into some of the many challenges in validating CGT manufacturing processes and analytical methods – and provides recommendations for designing potential strategies to meet them.
For manufacturing process validation challenges, the paper specifically addresses scenarios where there is a limited number of batches at commercial scale prior to and during process performance qualification (PPQ). Additionally, the unique challenges in designing PPQs for autologous cell therapies, specifically patient variability, and limited material availability.
Within the challenges of analytical method validation, the paper highlights the difficulties of assay variability and potency assay validation, including the evaluation of validation parameters and setting acceptance criteria. It also discusses the issues impacting the generation of reference standards, when every batch may be unique for cell therapies.
It is a great tool to make people aware of these CGT validation challenges, so they do not simply follow existing general biologics validation processes. It will also help readers consider potential solutions when designing their validation campaigns and processes, which will allow faster progress with fewer quality deviations.
Even if readers cannot design around these challenges, they can acknowledge them and have more transparent conversations with health agencies to progress regulatory acceptance. Addressing challenges as early as possible will help provide a clearer and faster path for successfully validating the process and analytical methods.
While the recommendations are only suggestions, they will help organizations devise strategies specific to their products in consultation with regulatory agencies. These solutions should be based on process/product understanding, prior manufacturing experience, clinical safety and efficacy of the product, and the extent of unmet medical needs.
The paper contains a summary of existing regulatory agency guidelines that are relevant to CGT, which can be used as a springboard for further investigation into other guidance.
Although the regulatory guidelines for validating CGT manufacturing processes are evolving, expectations for scientific robustness behind the validation strategies are unlikely to change. Therefore, this paper will help industry develop a robust process validation strategy through the life cycle of these novel therapies while supporting their successful commercialization.
The paper will be presented at the BPI East conference in Boston, USA, on 22 September 2021.