The ABCs of Product-Specific Guidances | Audio Transcript

SBIA: Welcome to the CDER Small Business and Industry Assistance (SBIA) Chronicles Podcast Series

Today’s topic: The ABCs of Product-Specific Guidances, otherwise knowns as PSGs.

PSGs help streamline generic drug product development, promoting timely approval of abbreviated new drug application, or ANDA, submissions and increasing drug competition, ultimately improving patient access to high quality and affordable medicines.

Today we are joined by Lei Zhang, Deputy Director of the Office of Research and Standards within CDER’s Office of Generic Drugs to discuss PSGs.

Lei: Thank you Steve, I’m happy to be here!

Product-specific guidances, or PSGs, describe the Agency's current thinking on the evidence needed to demonstrate that a generic drug is therapeutically equivalent to the corresponding reference listed drug, or RLD, product. An RLD is a listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its abbreviated new drug application (ANDA).

These guidances are unique to the generic drug development program. FDA’s Office of Generic Drugs (OGD) manages the PSG program and leads PSG development at the FDA, in collaboration with multiple disciplines and offices within the FDA. OGD’s ongoing scientific research under the generic drug user fee amendments (GDUFA) enables the Agency to make recommendations to support the identification of appropriate science-based methodologies and evidence for the development of many complex drug products.

SBIA: How can PSG help applicants?

Lei: PSGs for specific generic drug products assist the generic pharmaceutical industry with identifying the most appropriate methodology and approaches for developing generic drugs and generating the evidence needed to support ANDA approval. This includes in vivo and/or in vitro bioequivalence studies, dissolution testing methods, and various waiver options such as Biopharmaceutics Classification System or BCS-based waiver. A PSG also includes key science and research results to facilitate generic drug development.

Ultimately, PSGs help applicants to submit ANDAs to FDA with fewer deficiencies, which helps lead to more first-cycle approvals. Not only do PSGs address uncertainties and provide the Agency’s current thinking on product development questions, but they also make research and development decisions more efficient and cost-effective, and advance the opportunity for discussion of new or alternative generic drug development strategies, especially for complex generic drug products.

SBIA: It definitely sounds like PSGs are an asset to ANDA applicants. Can you expand upon how they especially benefit the development of complex generics?

Lei: Yes, by knowing FDA’s expectations on a specific product, generic drug applicants can have a better opportunity to efficiently allocate their product development resources. PSGs are a “value-added proposition” that provide a practical pathway where none existed. They may also provide a new path in addition to or instead of a previous one and provide clarity and transparency on options to demonstrate bioequivalence.

Complex generic drug products are typically harder to develop than non-complex generic drug products using traditional bioequivalence approaches because of the complex nature of active ingredients, formulations, routes of delivery, delivery systems or other complexities. FDA aims to issue PSGs for complex products as soon as scientific recommendations are available.

SBIA: And exactly how many PSGs are there?

Lei: Well, as of August 2021, FDA has published over 1,900 PSGs. Events that can initiate the development of a PSG include:

• Recently approved New Drug Applications (NDAs) and supplemental NDAs,
• FDA analysis of products without PSGs,
• Pre-ANDA meetings,
• Public requests,
• Comments submitted to PSG docket through www.regulations.gov,
• Controlled correspondences, or
• Citizen petitions.

As a commitment under the Generic Drug User Fee Amendments Reauthorization of 2017 (also known as GDUFA II), FDA will issue PSGs for 90% of non-complex New Chemical Entities approved on or after October 1, 2017, at least 2 years prior to the earliest lawful ANDA submission date. FDA has met the goal since GDUFA II. This goal does not include complex products as defined in the GDUFA II Commitment Letter.

SBIA: Wow, that’s pretty amazing. Where can people learn more about PSGs?

Lei: Along with being announced in the Federal Register, PSGs are published on FDA’s Product-Specific Guidances for Generic Drug Development webpage in batches on a quarterly basis and as needed as stand-alone postings. This webpage lists the guidances in alphabetical order and in a searchable and downloadable table according to the name of the active ingredient. The PSG table allows users to perform a text search of PSGs by active ingredient, or by RLD or reference standard numbers; filter search results using a text search box; and export search results in Excel, CSV, or PDF format. In addition, the webpage separates out newly added and revised guidances.

To further enhance transparency, FDA also provides information related to upcoming new and revised PSGs for complex generic drug products on a quarterly basis on the Upcoming Product-Specific Guidances for Complex Generic Drug Product Development webpage. OGD also recently published a PSG Snapshot for a quick reference to understanding the usefulness of PSGs.

SBIA: Thank you so much for joining us Dr. Zhang! All of these webpages are linked in the SBIA Chronicles newsletter that accompanies this podcast, and also from FDA’s Guidances webpage.

For additional training and information, SBIA offers many conferences, workshops and webinars providing in-depth discussion of generic drug development, including complex scientific issues to PSG development. Recent events include the 2021 Generic Drugs Forum and the 2021 PSG webinar. Recordings of all SBIA events are located on the SBIA Learn webpage at www.fda.gov/cdersbialearn. Be sure to stay connected with upcoming events by visiting www.fda.gov/cdersbia to sign up for SBIA email updates, and follow SBIA on LinkedIn.