February 2020 ~

On January 28, the FDA issued six final guidances on gene therapy (GT) manufacturing and clinical development of products, as well as draft guidance, describing the agency’s proposed approach to determining sameness of GT products for orphan drug designation and exclusivity purposes.

The final guidances provide the FDA’s recommendations for product developers on manufacturing issues and recommendations for those focusing on gene therapy products to address specific disease areas. According to the agency, the guidance documents incorporate input from many stakeholders and take a significant step toward helping to shape the modern structure for the development and manufacture of gene therapies.

The six final guidances address:

• expectations for the Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs);
• expectations for the Testing of Retroviral Vector-Based Gene Therapy Products for Replication Competent Retrovirus (RCR) during Product Manufacture and Patient Follow-up;
• considerations to evaluate regarding when to conduct Long Term Follow-Up After Administration of Human Gene Therapy Products; and
• supplemental detail regarding product development considerations in:
  • Human Gene Therapy for Hemophilia;
  • Human Gene Therapy for Hemophilia; and
  • Human Gene Therapy for Rare Diseases.

The FDA says the suite of documents has been issued in an effort to help advance the field of gene therapy while providing recommendations to help ensure that these innovative products meet the agency’s standards for safety and effectiveness.

The draft guidance, released alongside the six final guidances, provide detail on the FDA’s rationale on determining sameness of human gene therapy products under the agency’s orphan drug regulations for the purpose of orphan-drug designation and orphan-drug exclusivity. The documents highlight the specific factors that the FDA “generally intends to consider when determining sameness for gene therapy products” and “does not address sameness determinations for other types of products”.

According to the FDA announcement, the guidance is intended to assist stakeholders, including industry and academic sponsors who seek orphan-drug designation and orphan-drug exclusivity, in the development of gene therapies for rare diseases.

“The growth of innovative research and product development in the field of gene therapy is exciting to us as physicians, scientists, and regulators,” said FDA Commissioner Stephen Hahn, “We understand and appreciate the tremendous impact that gene therapies can have on patients by potentially reversing the debilitating trajectory of diseases. These therapies, once only conceptual, are rapidly becoming a therapeutic reality for an increasing number of patients with a wide range of diseases, including rare genetic disorders and autoimmune diseases.”

“As the regulators of these novel therapies, we know that the framework we construct for product development and review will set the stage for continued advancement of this cutting-edge field and further enable innovators to safely develop effective therapies for many diseases with unmet medical needs,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research. “Scientific development in this area is fast-paced, complex, and poses many unique questions during a product review; including how these products work, how to administer them safely, and whether they will continue to achieve a therapeutic effect in the body without causing adverse side effects over a long period of time.”

Source(s): FDA.gov; Lexology; Gene Online; JD Supra;