Dr. Mitchell Seymour, September 26, 2013

Seymour head shotBefore a clinical trial can begin, an Institutional Review Board (IRB) reviews and approves a proposed study with the goal to protect human subjects and to support Good Clinical Practice.  Cures Within Reach supports research involving off-label use of Food and Drug Administration (FDA)-approved drugs, also known as “repurposing”. Repurposed drug studies can differ in many ways from the FDA-approved, “on-label” use of said pharmaceuticals. These differences require special scrutiny by IRBs during their review of the clinical protocol. Differences can include:

Patient population - gender, age group, concurrent disease or organ function

Drug dose or dosing schedule - drug dose and/or frequency, duration or schedule of treatment

Drug formulation - drug delivery method, different excipients, different release properties

The FDA may ask IRBs to judge the risk to subjects imposed by such differences. If the changes result in elevated subject risk, the FDA expects IRBs to require the investigator to submit an Investigational New Drug (IND) Exemption Request or a full IND application to the FDA. This September, FDA finalized a Guidance Document to reinforce the respective roles of investigators, IRBs, and sponsors in determining the need for an IND. IRBs play a central and critical role in the safety of repurposing research.

So what happens if your study as designed needs an IND, but your trial was approved by your IRB without one?  Who is held accountable? According to FDA, their scrutiny would fall on you, your IRB, and your research institution.  As an IRB member and a regulatory professional, my advice to investigators is not to risk FDA scrutiny. If you think your study does not require an IND, be first prepared to defend your rationale to your IRB. However, if they disagree, be prepared for your next steps which include interacting with the FDA.

The IND submission is not as scary or burdensome as it may seem. The IND submission provides you with critical FDA feedback to improve study design and enhance patient safety.  This is especially critical if one of your goals is to formally broaden the FDA-approved drug label.  If you are an academic investigator, labeling change is not likely on your radar with this initial clinical study, but what if your study produces exciting results?  With your new data about their drug, the drug maker may contact you for additional research opportunities, and industry expects that such studies are conducted under an IND.

In addition to research opportunities, it is never too early to think about the clinical implications of your repurposing research. If your study is successful and provides patient benefit, how will the drug get to patients more broadly – strictly off-label use, or will it be marketed for this new indication by a company? Would the original drug maker consider a Supplemental New Drug Application (sNDA) to actually change its original drug label? Or could a company competitor be interested in your results and in taking the repurposed drug to market using a 505(b)(2) pathway? These specific issues are topics of further Cures Within Reach “Researcher Resource” blog posts, but many of these options are enabled with the IND.

So, when it comes to regulatory concerns, I encourage clinical investigators to take the “long view”. The IND can improve your repurposing research on the front end and broaden your options on the back end.  As an investigative tool, the IND is an opportunity for development and learning rather than a regulatory hurdle.

Read all Regulatory Roundup posts by Dr. Mitchell Seymour

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