The FDA recently hosted a webinar focused on the facilitation of generic drug product development through Product Specific Guidances, also known as PSGs. The CDER Small Business & Industry Assistance (SBIA) held a webinar titled Facilitating Generic Product Availability Through Product-Specific Guidances (PSGS) for 2024 on April 25th. The slides and recordings will soon be posted on the FDA’s website (keep your eyes open for the posting); they are worth the listen if you didn’t have a chance to listen live. The webinar provided an overview of the PSG program, provided some details on tailored recommendations for IR oral products, discussed suitability petitions and their impact on PSGs, provided more information on device information being listed in PSGs, discussed considerations for study population selection in BE studies with PK endpoints, and provided some instructions on navigating the FDA dissolutions method database as well as how the database is used with and relates to PSGs. My colleague Becky Welton will provide more details on the dissolution database presentation in a forthcoming blog.
Overall, the PSG program has evolved under the Generic Drug User Fee program to provide guidances sooner than was committed to under GDUFA II, and under GDUFA III will be providing guidances for both complex and non-complex generic products. The PSG goals under GDUFA III are to issue PSGs for 50% of the complex products approved after October 1, 2022 within two years of approval of the NDA and for 75% of the complex products within three years of NDA approval. A new provision in GDUFA III adds a commitment by the FDA to issue PSGs for 90% of all NCE NDAs approved after October 1, 2022 within two years of approval, rather than at least two years prior to the earliest lawful ANDA filing date. The inclusion of complex products and the relation of the PSG goal to the approval date may help reduce uncertainty for ANDA developers trying to meet NCE-1 dates where they previously had to guess at the BE study design and/or requirements based on the RLD label or by looking at other PSGs in the same class, but only if there were similar PSGs posted. PSGs can be requested, and the FDA will continue to work on posting PSGs for previously approved complex products to support generic product development.
The PSG forecast list, accessible here, has become more specific, listing not only what new PSGs are planned for development and PSGs are identified for revision, but now the month and year they are being targeted for release. The webpage also lists whether the product is complex or noncomplex and, for revisions, the page has added the reason for revision, such as editorial, minor, or major. This is a huge help to applicants contemplating Controlled Correspondence to ask BE questions. How many of us have submitted a CC asking about a BE approach only to have it rejected a day or two later when a PSG was published? Anyone else raise their hand besides me?
It is also frustrating and stressful to have a product in the clinic when a PSG is published that changes the in vivo approach. Been there, done that. I do not recommend it! While the FDA is now listing the month and year when it plans to issue a PSG, these projected posting dates may change quarterly with each update so it is still possible to be surprised that a new or revised PSG has had its timeline accelerated and has been posted, while a prospective applicant has their product in the clinic or has even submitted their ANDA for review. Thankfully, this too has been addressed in GDUFA III with an enhancement to the meetings process. Now, if you happen to get caught in either of these situations, the FDA has agreed to hold PSG teleconferences to discuss the impact of a new or revised PSG on an ANDA development program or application. There is also the potential to have an additional pre- or post-submission PSG meeting after the initial teleconference to further discuss the scientific rationale for an approach other than the one recommended in the PSG. Having participated in a PSG teleconference, I can verify that the FDA does a good job of explaining the origin and recommendations in the PSG. The subject study of that PSG teleconference remains ongoing, and the ANDA has not yet been submitted, but the teleconference provided the applicant some insight into the FDA’s thinking and how to formulate a clear justification to support the study that will be filed with their future ANDA.
As explained in the webinar, the enhancements to the PSG program under GDUFA III are designed to provide more support for prospective applicants as they develop new generic drug products, but prospective applicants must be active participants in the process. Ask for the PSGs that are missing from products in your pipeline and check in on the PSG webpage at least quarterly to stay in tune with new postings and revisions. Should you find yourself in the uncomfortable position of having started a study before a PSG is posted, please reach out to the FDA and request a PSG teleconference. These tools are here to facilitate and enhance generic drug product development so leverage them when possible to support your own product development and support increased access to generic medications for all.
