There are clearly defined pathways that define how a along which a drug can be approved. Deciding on the appropriate regulatory pathway for your drug development program is a process that requires an understanding of the content and purposes of sections 505(b)(1) and 505(b)(2) of the Federal Food, Drug, and Cosmetics (FD&C) Act. It also is the reason we frequently start assignments with a regulatory strategy – what may seem obvious often is not. ProPharma has assisted in the development of hundreds of drugs and biologics. For many of our clients, we have started with them in early development and continued on through product approval and beyond.
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The 505(b)(1) Regulatory Pathway
The 505(b)(1) pathway is used by Sponsors to obtain the approval of a new drug whose active ingredients have not previously been evaluated and approved by FDA. As you can imagine, this type of submission requires extensive research, including both clinical and nonclinical studies, demonstrating the product's safety and efficacy for the indication being sought. Because of the substantial amount of research and data that is required, 505(b)(1) NDA submissions can take many years to complete and require a significant amount of resources to get approved. The key to development for this route is the ability to move logically from one step to the next.
The 505(b)(2) Regulatory Pathway
The 505(b)(2) regulatory pathway is another type of NDA submission that can be used to obtain market approval. This type of submission differs from the 505(b)(1) NDA in that the product in question contains identical active ingredients as to a previously approved drug. As such, the data included in the submission can rely, at least partially, on the Agency's findings of safety and effectiveness related to another product.
For example, if a Sponsor reformulated a previously approved drug so that it can be taken as a liquid form instead of as a tablet or capsule, the company could use the 505(b)(2) pathway to minimize the amount of original data it would need to submit in support of its new drug. Further, this type of submission is commonly used for previously approved drugs being used for a new indication. The FDA can rely upon existing data showing that the reference drug is safe and effective, allowing the Agency to focus its attention on determining whether the changes made to the new drug alter its safety or efficacy.
Sponsors taking advantage of the 505(b)(2) regulatory pathway can experience a shorter drug development program that requires fewer resources than the 505(b)(1) regulatory pathway.
Choosing the Appropriate Regulatory Pathway
When deciding which regulatory pathway is best for your NDA submission, the following questions should be considered:
- Does the product consist of a New Chemical Entity (NCE)?
- Is the product a new or novel formulation?
- If it is an existing product, is it a new route of administration?
- Does any published literature exist?
While this is by no means an all-inclusive list, answering these four questions will help you determine which regulatory pathway is most appropriate for you and your product, which is a critical step in developing and submitting an NDA.
If your regulatory strategy guides you down the 505(b)(1) route, you must develop an application that includes all information necessary to prove the safety and efficacy of your novel active ingredient. This process will take time, and guidance and supporting information will need to be generated through clinical studies.
If, however, your regulatory strategy guides you down the 505(b)(2) route, your time to market will likely be shorter because you can rely, in part, on data from existing reference drugs.
Whichever route you take, it is important to know that the standard of approval is the same. All NDAs are judged with a risk-benefit analysis that doesn't change because the source of the data supporting the analysis is different.
