Nonclinical Testing Resources

Pitfalls of Changing the Salt of a Listed Drug

Pitfalls of Changing the Salt of a Listed Drug The 505(b)(2) registration pathway for new drug products allows the applicant of the new drug product to reference the literature and the FDA’s findings of safety and/or effectiveness (e.g., as listed on the Listed Drug product’s label) to fulfill various registration requirements. From a nonclinical perspective, […]
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New Nonclinical Guidance for 505(b)(2) Products: No Cause for Alarm

On October 15, 2015, the United States Food and Drug Administration (FDA) issued a new guidance for industry and review staff with more uniform recommendations for the nonclinical safety evaluation of approved drug substances that are reformulated or in which a new route of administration is proposed for a previously approved drug product. These products, […]
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Therapeutic Equivalence Ratings Under 505(b)(2)

The FDA listing of therapeutic equivalence (TE) ratings can be a murky area for products approved under 505(b)(2) applications. The concept of TE ratings emerged from FDA regulations for generics and revolve around the announcement that the FDA would publish a current listing of all of its approved drugs together with TE ratings. This was […]
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Don’t conduct unneeded tox studies

In April I presented a webinar under the auspices of the DIA concerning preclinical bridging. During this webinar, we discussed the need to fill the toxicology gaps that may have been created during the time since the original reference listed drug was approved. These gaps, I stated, has led to the unfounded belief that the […]
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Non-clinical bridging – Most 505(b)(2)’s Don’t Require Full Tox Package

I have just finished a webinar under the sponsorship of the DIA dealing with non-clinical bridging. In this post, I’d like to share one of the case studies from my presentation to illustrate what should be considered during development. The example is the development of gabapentin enacarbil by XenoPort/GSK for restless leg syndrome. Gabapentin enacarbil […]
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Endpoint for GI Toxicity Clarified

NSAIDs are known to induce gastrointestinal (GI) tract toxicity, notably upper GI tract. Drugs that suppress gastric acid secretion such as histamine type 2 receptor antagonists, proton pump inhibitors (PPIs), NSAIDs (e.g., COX-2 selective drugs), and misoprostol (a prostaglandin E analog that also has mucosal protective properties) have been studied for their ability to protect […]
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Reference Listed Drugs (RLDs):Can More Than One Be Used?

Recently we considered the case of a 505(b)(2) NDA without an RLD.  So let’s ask if  a 505(b)(2) NDA have more than one RLD? In a word, the answer is “yes”! When using the 505(b)(2) regulatory pathway, Sponsors may rely on the Agency’s previous findings of safety and/or efficacy of an already approved product which […]
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Metabolites: New safety testing requirements – impact on 505(b)(2)

For Valentine’s Day, FDA issued a new guidance on metabolite safety testing.  Essentially, it outlines the non-clinical testing that may be required when the metabolism in humans produces significantly higher amounts of the same metabolites in the animal species where the toxicology was assessed. As the guidance points out, recent advances in analytical technology have […]
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505(b)(2) – Part 2: The Assessment: Preclinical Review/Preclinical Plan

Rats, mice, dogs, pigs – ANDA folks don’t have to deal with testing generic products in animals.  As long as the excipients are previously approved, generic drugs don’t have to conduct any preclinical studies. 505(b)(2) development programs may need to include some preclinical studies depending mainly on whether the route of administration changes or FDA […]
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