The U.S. Food and Drug Administration (FDA) has released 81 new product-specific guidances (PSGs), reinforcing its ongoing commitment to expanding the development of high-quality, affordable generic medicines. The publication includes 54 guidances for products that currently lack approved generics, 28 guidances addressing complex drug products, and 44 newly issued PSGs. These documents cover therapies intended for conditions such as psoriasis, cystic fibrosis, and lung and thyroid cancers, among several other clinically significant areas.
Significance of Product-Specific Guidances
Once finalized, PSGs reflect the FDA’s current scientific and regulatory expectations for developing generic drug products and generating evidence required for Abbreviated New Drug Application (ANDA) approval. By setting clear standards for demonstrating pharmaceutical equivalence, bioequivalence, and ultimately therapeutic equivalence, PSGs serve as essential tools for manufacturers seeking to produce safe and effective alternatives to their reference listed drugs (RLDs).
The FDA reiterates that generic drug applicants must ensure that their products match the RLD in active ingredient, dosage form, strength, route of administration, and conditions of use. Demonstrating bioequivalence remains a central requirement, and, as outlined in 21 CFR 320.24, this can be established through in vivo studies, in vitro studies, or a combination of both. The choice of methodology depends on the purpose of the study, the analytical methods available, and the characteristics of the drug product. Applicants are encouraged to consult the Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for ANDAs, published in August 2021, as a foundational resource in study planning.
Enhancing Access to Affordable Generic Medicines
The issuance of PSGs directly supports the Agency’s mission to improve public health by accelerating the development, assessment, and approval of generic drugs. By clarifying regulatory expectations, PSGs help streamline ANDA submissions and reduce uncertainties in study design and development pathways. These efforts align with the FDA’s Drug Competition Action Plan and advance the objectives of Executive Order 14273, “Lowering Drug Prices by Once Again Putting Americans First,” which emphasizes the need to strengthen market competition and expand patient access to safe and effective treatments.
Clear and timely guidance contributes to a more predictable regulatory environment, ultimately fostering greater availability of generics and improving affordability for patients and health systems.
Implementation Under GDUFA III
The newly issued guidances are published in accordance with commitments under the Generic Drug User Fee Amendments Reauthorization of 2022 (GDUFA III), which took effect on October 1, 2022. Under these commitments, the FDA will issue PSGs for at least 50 percent of complex products approved in new drug applications on or after October 1, 2022, within two years of approval, and for 75 percent of such products within three years. The Agency continues to develop guidances for complex products approved prior to this date that do not yet have an established PSG.
For non-complex new chemical entities approved on or after October 1, 2022, the FDA aims to issue PSGs for 90 percent of these products within two years of approval. When determining priorities for PSG development, the Agency evaluates requests from industry and other stakeholders, the availability of specific drugs, public health needs, safety considerations, and emerging data from ongoing GDUFA-supported research.
Considerations for Sponsors and Investigators
The FDA highlights the importance of reviewing current RLD labeling when designing IND-exempt pharmacokinetic, pharmacodynamic, bioequivalence, or bioavailability studies intended to support ANDA submissions. Boxed warnings, contraindications, warnings and precautions, and adverse reactions listed in the labeling should guide the selection of study participants, inclusion and exclusion criteria, safety monitoring, and other clinical considerations.
Some PSGs also provide information on data and submission format requirements. Under Section 745A(a) of the Federal Food, Drug, and Cosmetic Act, electronic submission standards outlined in Agency-wide guidances are mandatory once finalized. Sponsors are encouraged to contact the Center for Drug Evaluation and Research (CDER) with questions regarding electronic submissions or dataset preparation.
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Written by Nare Hovhannisyan, MD