505(b)(1) vs. 505(b)(2): Choosing the Appropriate Regulatory Pathway

August 12, 2020

Because the FDA is an agency established by a federal law, there are clearly defined pathways 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.

The 505(b)(1) Regulatory Pathway

The 505(b)(1) regulatory pathway is the “traditional” New Drug Application (NDA) process. Sponsors use this pathway to obtain the approval of a new drug with active ingredient(s) that have not previously been approved by FDA.

The data package necessary for approval of this new drug requires prospective demonstration of clinically meaningful treatment benefits and statistically significant safety and efficacy after an extensive clinical development program entirely conducted by or for the sponsor, without allowance for reference to third party data.

The 505(b)(2) Regulatory Pathway

The 505(b)(2) regulatory pathway is an alternative NDA process for approving a new drug that contains the same active ingredient as a previously approved product. It was established by the Hatch-Waxman Amendments of 1984 with the intention of allowing sponsors to obtain approval of NDAs containing investigations of safety and effectiveness that were not conducted by or for the sponsor.

The effect of this section is the avoidance of unnecessary duplication of studies that have already been performed on the reference drug. Essentially, by following the 505(b)(2) pathway, sponsors can rely upon clinical data or literature produced by other companies and entities.

For example, if a sponsor reformulated a drug so that it can be taken in liquid form instead of tablet or capsule form, 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. The FDA could 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.

Speaking strategically, this pathway may be attractive to sponsors operating without a large amount of resources. That’s because these sponsors tend to need a shorter runway to approval and the 505(b)(2) shortens the time and expense involved with getting a drug approved.

Choosing the Appropriate Pathway

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 new active ingredient. This process will require time and guidance, and supporting information will need to be generated through clinical studies that you must conduct.

If, however, your regulatory strategy guides you down the 505(b)(2) route, your time to market will likely be shorter because you are able to 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.

Let Us Guide You Along the Appropriate Pathway

Choosing the right regulatory pathway is critical to the success of your drug development program. You must choose wisely to make certain that you are headed in the right direction.

Because sections 505(b)(1) and 505(b)(2) each have their own requirements, your drug development program will benefit from the assistance of the experts at ProPharma Group. We will help you decide upon the appropriate regulatory pathway for your product. Regardless of which pathway fits your development plan best, we’ll be there to ensure that your discussions with the FDA are properly framed to fit the chosen pathway and guide your product through the approval process.


FDA Outlines Policies for Compounding Drug Products That Are Essentially Copies of Approved Drugs Under Section 503B of the FD&C Act

In our preceding FDA News article, we focused on the content of the first draft guidance, which addresses restrictions concerning the compounding of drug products that are essentially copies of...

July 18, 2016

FDA Outlines Policies for Compounding Drug Products That Are Essentially Copies of Commercially Available Drugs Under Section 503A of the FD&C Act

On Thursday, July 7th, the FDA issued two draft guidance documents regarding the compounding of drugs that are essentially copies of commercially available or approved drugs. In these documents,...

The 503b Outsourcing Facility Compliance Dilemma

At the time of this writing, there were 59 registered 503b outsourcing facilities posted on the FDA’s website. All firms that had been inspected were issued FDA inspectional observations in the form...