Explore the FDA’s new draft guidance for cell and gene therapy (CGT) products. Learn key insights on risk evaluation, comparability studies, and the importance of quality management systems for successful manufacturing changes.
In August 2020, the Food and Drug Administration (FDA) announced a draft guidance for industry titled Cellular & Gene Therapy. The guidance is intended to provide suggestions to enhance the safety and effectiveness of these advanced and emerging therapies.
There are challenges in the manufacturing of CGT products given their inherent complexities. It usually involves the use of living cells, one of the reasons that make the manufacture relatively difficult to control and standardize. In the translation of this CGT, any change in manufacturing could compromise the final quality and final performance. Manufacturing changes must be well controlled and assessed for impact on product safety and efficacy.
What You Need to Know from The FDA Draft Guidance
Risk Evaluation for Getting Design Changes into Manufacturing:
Preliminary draft guidance reinforces the idea that risk needs to be evaluated with each manufacturing change. Consider factors such as the type of change, how it might affect product quality and whether you have data to back up the change.
Performing Comparability Studies
Comparability Studies — To be used to assess the impact of changes in manufacturing on product quality. These are quality attribute evaluations that compare the product prior to change and product after change.
How to Report Manufacturing Changes to the FDA:
Sponsors of Investigational New Drug Applications (INDs) and applicants of Biologics License Applications (BLAs) for CGT products must communicate with the FDA regarding all manufacturing changes. This would guarantee transparency and regulatory visibility over the product evolution.
Directions for Comparison Studies:
Comparability by Lifecycle Approach:
The draft guidance also stresses the need for a lifecycle perspective to comparability. The other is a holistic end-to-end approach, that looks at the product lifecycle from manufacture through clinical use to determine how changes will affect the quality of the final product.
Comparability Risk-Based Writing Approach
These critical quality attributes of the product should be assessed, and a risk-based evaluation conducted to determine their impact on the potential manufacturing changes. With that, they can tell which areas are needed for further review and monitoring.
Different Methods for Comparability Assessment:
Comparability can be assessed using a range of methods, including analytical, animal and clinical studies. These approaches allow for a complete assessment of the effects of process changes on product quality.
Notable Points in the Draft Guidance
1. Complete QMS:
In its guidance, the FDA not only includes a requirement for a QMS but also wants sponsors to have a strong and reliable quality management system in place that ensures CGT products are fully designed with properly controlled materials and manufacturers as well.
2. Risk Identification and Risk Assessment Risk-Based Approaches for Identifying and Assessing Risks
Sponsors are encouraged to apply risk-based approaches for evaluating and identifying manufacturing changes. This allows the target of resources to easily detect the most critical nodes.
3. Communication and Group based (Collaboration) tasks:
This advice highlights the importance of continued communication and collaboration between sponsors and FDA. Ongoing dialogue across the lifecycle of a product allows for the exchange of essential information and verifies aligning with regulatory compliance.
Conclusion
For INDs and BLAs — The FDA draft guidance on CGT products provides an important reference for any manufacturing changes and comparability. It provides very specific suggestions and tactics for dealing with the complexities of the Manufacturing of these advanced therapies. The guidance aims to improve the quality management and risk assessment of development and production for CGT products in their entire life cycle.
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