A Brief Overview of the 505 Regulatory Pathways

The FDA recognizes three primary pathways for the approval of new drugs and abbreviated new drug applications (ANDA): the 505(b)(1) NDA, 505(j) ANDA, and 505(b)(2) NDA.

Each pathway serves a distinct purpose in the drug approval process.

505(b)(1) NDA
The 505(b)(1) NDA is a comprehensive application that relies entirely on original data. Every study conducted under this pathway is specifically tailored for the drug by the sponsor and serves as the foundational data for FDA approval.

This pathway is the most resource-intensive and time-consuming of the three.

505(j) ANDA
This pathway is designed for the approval of generic drugs. The 505(j) ANDA becomes relevant when a patented innovator drug is approaching its expiration.

The central criterion for approval through this pathway is demonstrating bioequivalence to the innovator product. For oral dosage forms, a food effect study is typically required to ensure similar efficacy and safety profiles.

505(b)(2) NDA
A “hybrid application,” the 505(b)(2) NDA, combines aspects of both the full NDA and ANDA. This pathway is ideal for modified or improved versions of existing innovator drugs, leading to the creation of a distinct drug product with its own exclusivity rights.

The process incorporates pre-existing data and new findings to facilitate a more efficient approval process. In Europe, a similar process is known as the Hybrid application, reflecting its combined nature.

The Benefits of the 505(b)(2) Pathway
In short, the 505(b)(2) pathway offers pharmaceutical companies a strategic advantage by reducing the time and financial investment typically required for the conventional full NDA. This approach bypasses the necessity for numerous nonclinical studies and extensive safety and efficacy tests.

The 505(b)(2) pathway specifically benefits new drugs that are similar to already approved drugs but have slight variations in formulation or administration routes. Before the Waxman/Hatch Act, approval for such drugs depended on extensive literature-based arguments provided by the applicant to prove the safety and efficacy of the new product.

Applicants can now reference the safety and efficacy data of the original innovator drug without needing a right of reference.

While some differences in formulation or administration might require additional clinical studies for 505(b)(2) applicants, these are typically less extensive than what’s required for original innovator drugs. In many cases, a bioequivalence study suffices to demonstrate the similarity between the two drugs, leading to FDA approval. In instances where additional clinical studies are needed, the requirements are generally less stringent.

The pathway also presents an opportunity for market exclusivity ranging from 3 to 7 years.


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Resource Person: Diwakar Shukla

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