PhRMA Suggests Revisions to Cell Therapy Guide
Pharmaceutical Research and Manufacturers of America (PhRMA) says FDA should revise its recommendations for sponsors requesting meetings concerning cellular and gene therapy products (CGTs) to better align with the drug user fee program’s commitment letter and existing agency procedures. PhRMA suggests this in just-posted comments on a draft guidance entitled “Frequently Asked Questions — Developing Potential Cellular and Gene Therapy Products.” The document is intended to provide industry with answers to frequently asked questions (FAQs) and commonly faced issues that arise during cell/gene therapy development. The FAQs cover multiple disciplines, including regulatory review, chemistry, manufacturing, and controls, pharmacology/toxicology, clinical, and clinical pharmacology.
In particular, PhRMA says it is concerned that the draft is “adding to the prerequisites” for industry to request an early development “INTERACT” meeting by having expectations that at least some proof-of-concept studies will be complete prior to such a meeting. The group says the agency has previously noted that advice on proof-of-concept studies is an example of the kind of topics to discuss in an INTERACT meeting
PhRMA also says that while the guidance does indicate chemistry, manufacturing and controls (CMC) topics can be discussed as part of an INTERACT or pre-IND meeting, it encourages FDA to provide a CMC-specific meeting option for sponsors because CGT Products raise unique CMC complexities. “To ensure that sponsors are able to discuss critical CMC issues with FDA in a timely manner, an INTERACT (or other) meeting focused exclusively on CMC could be highly beneficial, particularly given FDA’s expectations described above about the appropriate number of questions per meeting,” the group says. “Moreover, because critical CMC questions may arise at various points in early clinical development, we recommend that FDA adopt a flexible approach regarding the timing of a CMC-specific meeting.”
Additionally, PhRMA encourages FDA to provide added flexibility on using non-traditional study designs. The group supported the guidance’s acknowledgment that in some cases a well-conducted natural history study may serve as an acceptable external or historical control. However, it suggests that FDA also reference other illustrative examples of external controls covered in existing guidance, such as data from another trial and sources of real-world data, and to confirm such flexibilities for using external on a case-by-case basis. “Moreover, since gene therapy treatments are often designed for a single dose and FDA has approved gene therapies where a dose-response relationship has not been identified, we encourage the agency to clarify its expectation for evaluating more than one dose, including expectations for establishing a dose-response relationship and for dose selection for the pivotal trials.”