Lisa,
The most critical aspect of a 505(b)(2) is the reference listed drug (RLD). You have to identify the RLD in order to be a 505(b)(2) and if the product is not approved in the US, I don't see how you can identify the RLD. The other key aspect is you have to bridge any differences of the new drug to the RLD beginning with the active ingredient. I agree that the published information may be useful in supporting the concept and rationale for development but it won't likely be useful in approval since the information and data to support any required information won't be available to FDA. Even if supportive you have to describe how it is useful and supportive. In addition, as indicated, you would have to use the drug in a clinical trial, then it will become an investigational agent as it is not approved in the US, which adds further complexity to the strategy. My advise would be to generate your development plan, nonclinical and clinical, and present your plan to the Agency. The issue of defining your regulatory path at this point is secondary to getting the agency to agree or comment on your investigational plan. In the end you have to generate the required data for approval in the US.
I have just lived through 2 505(b(2) discussions with the FDA and the results were that the programs proposed were robust enough to stand on their own for approval. There was more work to use the 505(b)(2) pathway than a 505(b)(1).
All the best,
Dar
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Darlene Rosario MBA, RAC
Principal Consultant RA, Quality and Compliance
Velocity Consulting
Ventura CA
United States
Original Message:
Sent: 11-06-2015 08:13
From: Ravi Harapanhalli
Subject: 505(b)(1) or 505(b)(2) pathway
Since NCEs/NMEs are eligible for 505b2 pathway under certain circumstances, I don't believe a proposed drug has to have been previously approved and/or marketed within the US for this pathway to be viable. If your drug is a pro-drug or active metabolite of a drug approved in the US, then that makes things easy. If not, you may want to see if your proposed drug has similar pharmacologic effects/same pharmacologic class as one approved in the US. Considering that your proposed drug has had several years of exposure information OUS, and assuming adequate and reliable literature is available, you may be able to justify for this pathway. However, as mentioned by others, you will have to do some PK/PD bridging studies to justify reliance on the published literature and depending on the indication being sought and route of administration, additional nonclinical and/or clinical bridging. Best recommendation is to approach FDA with a pre-IND meeting and lay out your strategy.
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Ravi Harapanhalli
Potomac MD
United States