NIH RAC Changes

The changes to the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC) protocol review and reporting structure, which were reflected in changes to the Federal Register on August 17th, 2018, will affect gene and cell therapy Sponsors in these three significant ways.

Therapies to Patients

The changes to the review and reporting structure reflect the changing landscape of gene and cell therapy being regarding in the drug development landscape as viable and realistic therapies for treating, and possibly curing, diseases. These therapies, which were at one point considered to be the “wild west” therapies of medicine, are becoming more mainstream and there has been a shift in the thinking of the regulators. The roadblocks and pinch points to developing gene therapies, which cost Sponsors time and money, are being removed from today’s drug development pathways. Most importantly, these NIH/RAC changes mean that efficacious and truly promising therapies can get to sick patients who need these therapies the most. Many gene and cell therapies that are being developed are meant to treat patients who have a great unmet need and who have limited treatment options, if they have any options at all.

Time Constraints

Alleviating time delays and time constraints may be *the* most important change for Sponsors who are trying to develop gene and cell therapies. The NIH/RAC meets only 4 times a year. The Appendix M, containing the clinical study plan, had to be submitted ~8 weeks prior to the posted RAC meeting date. In order to submit Appendix M to the NIH/RAC a Sponsor needed to first obtain an IBC letter to accompany the Appendix M submission stating whether or not the IBC recommended, or did not recommend, a public meeting for the protocol. All of this had to be done in order to follow the proper procedure for registering a protocol with the NIH. The IBC review and assessment could take a few weeks or a few months. Then, if it was determined that a Sponsor did in fact need a public meeting, there was preparation time involved in that process as well. Lastly, the RAC recommendations issued at or after the meeting needed to be addressed and/or incorporated into the study protocol and study plan. All of these steps had to occur prior to an IND submission to the FDA for review. This process could significantly delay the submission of an IND and the start of the clinical trial. These proposed new changes to the NIH/RAC will eliminate all of this lag time prior to an IND submission.

Burden of Duplicate Reporting

Once a gene or cell therapy protocol is registered with the NIH/RAC, another requirement is for a Sponsor to submit the following to both the NIH/RAC and to the FDA:

• Annual Reports/DSURs,
• Protocols and Amendments
• Clinical investigator information and
• Serious Adverse Events (GeMCRIS Safety database)

The purpose of this was to ensure that both the NIH and the FDA had the same documents available, which could lend itself to seamless discussion, review, and understanding of a therapy and the progress of a product. It was also required in order to make discussions between the two Agencies easier. What this meant for Sponsors was duplication of submissions. Submissions that go to the FDA are electronically submitted via the Electronic Submission Gateway (ESG) in a specific CTD format. However, the NIH does not have an ESG, so every submission had to be re-formatted and/or re-published in order to submit it to the NIH/RAC via a bookmarked PDF and an e-mail attachment(s). Therefore, every submission turned into 2 individual and distinct submissions done in entirely different ways.

The changes to the NIH/RAC review process means that therapies will get to the patients who need them faster, that cell and gene therapy companies will not face as many delays to IND and first-in-human clinical trials, and that the burden of duplicative reporting will be eliminated.

Reference: New England Medical Journal