Expanding Generic Approval Benefits Pharmaceutical Manufacturers & Patients

Andrew Thompson

Associate Editor

Loyola University Chicago School of Law, JD 2023

Prescription drug consumers are often left frustrated when confronted with limited generic versions, if any are available, and must resort to paying out-of-pocket for their prescriptions. This is due in part to how the FDA evaluates and approves new drug products prior to market entry. Applications for FDA approval of a drug product reach the FDA by pathways established under the federal Food Drug & Cosmetics Act (FDCA).

Under FDCA § 505(j), which is codified at 21 U.S.C. § 355, a manufacturer may submit an abbreviated new drug application (ANDA) which seeks FDA approval for a drug which shares the intended function of an existing FDA approved drug product designated as the reference listed drug (RLD). To determine whether the drug product is sufficiently similar to the RLD, the FDA requires manufacturers to submit information demonstrating that the drug is bioequivalent to the RLD. Bioequivalence means the drug product has the same active ingredient(s), dosage form, route of administration, strength, previously approved conditions of use, and labeling. While the 505(j) pathway is robust in terms of safety mechanisms aimed at protecting consumers, the 505(j) clearance becomes unavailable to manufacturers when the drug product differs in one or more of the domains listed above, such as dosage. As a result, drug products which are safe and efficacious, albeit at a different dosage from the RLD, become ineligible for 505(j) approval. In turn, fewer generics can enter the market or must enter the market through a slower approval pathway.

New legislation aims to expand 505(j) approval

In response to the cost and time constraints imposed on manufacturers and a desire to bring more affordable generics to market, Senator Bill Cassidy (R-LA) introduced Senate Bill 1462 – Simplifying the Generic Drug Application Process Act (SGDAPA). This legislation aims to expand the generic approval process covered in FDCA § 505(j). This Act reaches across the aisle and has the support of co-sponsor Senator Tina Smith (D-MN), who introduced the Affordable Medications Act. The SGDAPA would amend subparagraph (C) of 505(j)(2) such that “a person may submit an abbreviated application for a new drug that has a different dosage form or strength from that of a listed drug.” This change in drafting will have a significant impact on the generics process by allowing a drug product which is the subject of an ANDA seeking 505(j) approval to gain FDA approval when the new drug differs from the RLD in terms of administration but does not differ in function. By expanding the language of FDCA § 505(j) to cover drug products with a different dosage form or strength, generic manufacturers will see increased revenue while consumers will likely see a decrease in the cost of their medication with respect to the cost of a non-generic prescription.

Revising standards for generic approval

The Prescription Drug User Fee Act (PDUFA) provides a mechanism for the FDA to collect fees from manufacturers selling and marketing FDA approved drug product in the U.S. Fees collected under PDUFA are used to support FDA actions. The PDUFA is renewed in five-year terms, with PDUFA’s August 2017 renewal set to expire in September 2022. Similarly, the Generic Drug User Fee Amendments (GDUFA) provides a mechanism for collecting fees from manufacturers of generic drug products and was last authorized in August 2017 on a five-year term. The GDUFA will expire in September 2022. Given the opportunity to amend the GDUFA and PDUFA prior to the upcoming renewals, Professor of Law Racheal Sachs at Washington University states “I would not be surprised at all to seem some reforms to the accelerated approval process as part of the PDUFA legislation.”

One potential change to the ANDA pathway under PDUFA revisions is suggested by Jeremy Sharp, former FDA deputy commissioner, who states a revision could establish a “more rigorous step for identifying and accepting and using a surrogate endpoint.” Surrogate endpoints represent indirect proof of a drug product’s efficacy based on a beneficial effect following administration of a drug product, such as a reduction in beta-amyloid following administration of aducanumab. Adopting a clearer framework for defining and setting surrogate endpoints would allow manufacturers such as Biogen to anticipate and meet the FDA’s requirements for new drugs such as Aducanumab, which was reviewed on an accelerated basis by the FDA. The FDA provides in its PDUFA commitment letter titled “PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2023 Through 2027” that the FDA will direct fees collected under the PDUFA toward the formation of review teams tasked with developing new surrogate endpoints. As a result, a change to legislation which on its face is aimed at collected fees will in fact provide the FDA with the legislative support necessary to enhance the review and approval of new drug products and the approval of new generic drug products.

Generic Approval by the FDA

Recent generic approvals support the rationale of the revisions under the PDUFA. In 2022, seven drug products including one related to the treatment of Parkinson’s Disease were granted first-time generic approval from the FDA. While the market entry of generic drugs for the treatment of Parkinson’s Disease is both noteworthy and a long-awaited step for many patients and their families, seven generic approvals supports the rationale of the Act by highlighting the inability of 505(j) as currently drafted to cover potential subjects of an ANDA. The change in drafting which would take effect under the Act would likely lead to an increase in the rate and quantity of drug products granted FDA approval under 505(j).