FDA Offers GDUFA III Insight

Tens of thousands of generic drugs are available today, which have all been evaluated by FDA and proven to work in the same way and provide the same clinical benefit and risks as their brand-name counterparts. In this article, we discuss FDA resources available to generic drug producers and manufacturers that may further illuminate the abbreviated new drug application (ANDA) process along with the implementation of the Generic Drug User Fee Amendments (GDUFA).

What is GDUFA?

Iilun Murphy, MD, Director of the Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research (CDER)

GDUFA was designed to facilitate the delivery of safe and effective generic drugs to the public and improve the predictability of the ANDA assessment process. GDUFA is based on agreements between FDA and representatives of the generic drug industry and authorized by the US Congress. Since 2012, GDUFA has been reauthorized twice, with the reauthorization occurring every five years. The most recent reauthorization was in September 2022. We are currently under the third GDUFA cycle (GDFUA III: October 2022 to September 2027). Funding from GDUFA expands FDA’s capability to conduct generic drug research that helps inform FDA guidances and policy, which facilitates generic drug development and regulatory assessments of generic drug applications and, in the end, helps facilitate patients’ more timely access to generic medicines.

Research and science

In addition to pre-ANDA program features and meeting schedules (more to be discussed below), GDUFA provides the funding for a robust regulatory science program at FDA that addresses scientific challenges that may delay the development of generics. The GDUFA science and research program¹ supports the development of innovative methodologies and more efficient tools to help establish drug equivalence standards that guide the development of safe, effective, and high-quality generic drug products, including complex generics. GDUFA science and research are particularly important for complex products, which are harder to develop as generics and for which there are often few generic products (or none).

GDUFA III changes

The implementation of FDA’s commitments under GDUFA III went into effect on October 1, 2022.² As with the GDUFA II cycle, FDA is fulfilling new enhancements agreed to in the GDUFA III commitment letter³ for the pre-ANDA program⁴ and ongoing ANDA processes. There is now more clarity for current and prospective applicants looking to develop new generic drug products along with new enhancements to the program designed to maximize the efficiency and utility of each assessment cycle with the intention of reducing the number of cycles overall in the ANDA review process.

The pre-ANDA program features product development, pre-submission, and mid-review cycle meetings. In particular, product development and pre-submission meetings⁵ provide clarity around regulatory expectations for prospective applicants early in the generic product development cycle and assists with the development of more complete application submissions. The goal of the program is to help reduce a generic drug’s time in the pipeline from concept to development to approval.

Under GDUFA III, more meetings are available to prospective applicants before they submit an ANDA to assist prospective applicants in developing more complete submissions, promote a more efficient and effective ANDA assessment process, and reduce the number of assessment cycles needed to obtain ANDA approval. GDUFA III also provides more meetings to ANDA applicants in an effort to provide, or continue to provide, targeted, robust advice as they work to meet the requirements for approval. (To learn more about new and redesigned ANDA meetings under GDUFA III that expand beyond the pre-ANDA phase, please view FDA’s infographic, GDUFA III| Summary of T-cons & Meetings.⁶)

Product-specific guidances and GDUFA

A specific example of work enhanced by GDUFA science and research is FDA’s development of product-specific guidances (PSGs). FDA utilizes scientific research outcomes to inform PSGs. PSGs describe FDA’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference listed drugs. These PSGs further facilitate generic drug product availability and assist generic drug developers with identifying the most appropriate methodology for developing drugs and generating the evidence needed to support ANDA approval.

Under GDUFA III, new goal dates are implemented for newly approved complex products in addition to PSGs for newly approved non-complex new chemical entities. When a new or revised PSG is published and an applicant or prospective applicant has already commenced an in-vivo bioequivalence study, the applicant or prospective applicant may request a PSG teleconference to obtain FDA feedback on the potential impact of the new or revised PSG on its development program. Pre-submission or post-submission PSG meetings may be requested following feedback received at the PSG teleconference (see GDUFA III | Summary of T-cons & Meetings⁶).

Resources

Generic drug makers can find numerous resources on the FDA.gov website that can help with the application process and provide transparency on the progress and performance of FDA’s generic drugs program. To learn more, visit the Office of Generics at FDA.gov.

References

1. FDA, “Science & Research,” accessed August 2023. https://www.fda.gov/drugs/generic-drugs/science-research
2. FDA, “GDUFA III Reauthorization,” accessed August 2023. https://www.fda.gov/industry/generic-drug-user-fee-amendments/gdufa-iii-reauthorization
3. FDA, “GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027,” accessed August 2023. https://www.fda.gov/media/153631/download
4. FDA, “Pre-ANDA Program,” accessed August 2023. https://www.fda.gov/drugs/generic-drugs/pre-anda-program
5. FDA, “GDUFA III Enhancements to the Pre-ANDA Program,” accessed August 2023. https://www.fda.gov/industry/generic-drug-user-fee-amendments/gdufa-iii-enhancements-pre-anda-program#development
6. FDA, “GDUFA III Commitment Letter | Summary of T-cons & Meetings,” accessed August 2023. https://www.fda.gov/media/162239/download

About the author

Iilun Murphy, MD, serves as the director of the Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research (CDER). This office is responsible for the review and approval of abbreviated new drug applications. OGD’s mission is to ensure, through a scientific and regulatory process, that generic drugs are safe and effective for the American public. Recently, Murphy oversaw the implementation of the Generic Drug User Fee Amendments’ goals and review management activities. Additionally, she was integral in the creation of the first Generic Drug Global Cluster, a collaborative forum for the world’s leading regulatory agencies. Murphy is a board-certified pediatrician and an assistant clinical professor of pediatrics at The George Washington University School of Medicine.