FDA Issues Six Final Guidances, One Draft on Gene-Therapy Mfg and Development

By Emily Forster -

February 13, 2020

The US Food and Drug Administration (FDA) has issued six final guidances relating to manufacturing and clinical development of gene therapies and a draft guidance relating to gene therapies and orphan-drug designation.

The six final guidances provide the agency’s recommendations for product developers on manufacturing issues and recommendations for those focusing on gene-therapy products to address specific disease areas.

In issuing these six guidances, the FDA explained that the scientific review of gene therapies includes the need to evaluate highly complex information on product manufacturing and quality. In addition, the clinical review of these products frequently poses more challenging questions to regulators than reviews of more conventional drugs, such as questions about the durability of response, and these questions often can’t be fully answered in pre-market trials of reasonable size and duration.

“For some gene therapy products, therefore, although they have met the FDA’s standards for approval, we may need to accept some level of uncertainty around questions of the duration of the response at the time of marketing authorization,” said the FDA in a January 28, 2020 statement. “Effective tools for reliable post-market follow up, such as post-market clinical trials, are going to be key to advancing this field and helping to ensure that our approach fosters safe and innovative treatments.”

The six final guidances are: (1) Chemistry, Manufacturing, and Control Information for Human Gene Therapy Investigational New Drug Applications; (2) Human Gene Therapy for Retinal Disorders; (3)Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up; (4) Human Gene Therapy for Rare Diseases; (5) Human Gene Therapy for Hemophilia; and (6) Long Term Follow-Up After Administration of Human Gene Therapy Products.

The draft guidance, Interpreting Sameness of Gene Therapy Products Under Orphan Drug Regulations, provides the FDA’s proposed current thinking on an interpretation of sameness between gene-therapy products for the purposes of obtaining orphan-drug designation and eligibility for orphan-drug exclusivity. The draft guidance focuses on how the FDA will evaluate differences between gene-therapy products when they are intended to treat the same disease. As laid out in the draft guidance and the FDA’s regulations, the agency says its determination will consider the principal molecular structural features of the gene-therapy products, which includes transgenes (the transferred gene) and vectors (the vehicle for delivering the transgene to a cell).

Source: US Food and Drug Administration