Preparing for Your First IND Submission: The Devil is in the Details - When preparing an IND submission, an open mind and ability to - BioPharm International

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Preparing for Your First IND Submission: The Devil is in the Details
When preparing an IND submission, an open mind and ability to


BioPharm International
Volume 21, Issue 1


Conrad J. Heilman, Jr.,PhD
In the process of developing breakthrough biopharmaceuticals with profound therapeutic promise, the many detailed requirements for a successful investigational new drug (IND) submission may seem petty, but they are not. With an IND, you are essentially moving from the cloistered world of the laboratory into a highly regulated industry where details not only matter, but are also greatly magnified by the overriding requirements of safety and efficacy. Treat those details with forethought and you will eventually succeed. Treat them as an afterthought and all of your pioneering science, state-of-the-art technology, and therapeutic ambition could come to nothing. At the very least, your progress to market could be delayed significantly. And if, like most young biopharmaceutical companies, you are on a short financial leash, such delays can be fatal for securing additional funding.

Based on our experience working with biotechs and the FDA, we have found that by adhering to the following principles you can greatly increase your chances of a timely and successful IND submission.

BEGIN AT THE BEGINNING

Many first-time applicants greatly underestimate the time that it takes to prepare and submit a well-designed, well-executed IND. From the time you have a genuine clinical candidate, you can typically plan on at least a two-year time frame to gather sufficient information to file an IND and submit it to the FDA. Companies that devote methodical, systematic attention from day one move far more efficiently toward clinical trials than companies who delay. Ideally, even before the research phase, you should study the relevant FDA instructions and forms for an IND submission, which can be found on the FDA's web site, and determine how your organization can best meet those requirements.

DO THE SCIENCE RIGHT

The science behind the drug should be rigorous and so should the records of it. It is not unusual for products originating in discovery environments to be missing a detailed, well-documented historical chain of events, and hazy origins will often raise serious issues and not satisfy FDA reviewers. You must design and document a comprehensive list of all toxicity and other preclinical studies that will answer most of the critical questions about your product's origin, characteristics, safety, and efficacy in laboratory tests and models. If you don't have a pharmacologist on staff, you should seek help to make sure that you can demonstrate the pharmacology.

The failure to design, execute, and document the right studies from the outset can come back to haunt you—and set you back by years. For example, one biopharmaceutical developer, working with a promising reengineered cell line that produced a particular protein, mapped the genes but failed to do sequencing analysis of the genes because the organization didn't believe it was necessary. However, one persistent scientist insisted that without sequencing analysis, it was impossible to know if any mutations might exist in the construct. When the line was sent out for a nucleotide map analysis, it came back with several mutations in the gene of interest. If the organization had not discovered the mutations and had gone to the FDA two years later with their IND, the agency would have asked for that analysis and the developer would have been back at square one. Instead, the developer was able to reengineer the line early on, lost very little time, and was able to supply the FDA with all of the required information about the cell line.

Unfortunately, when some companies find themselves before the FDA with inadequate data, they go into survival mode and defend the product or technology, arguing that the agency should approve the IND anyway. Doing this runs the risk of losing credibility with the agency on all counts. If you do the science right in the first place, you can avoid putting yourself in that position.

DOCUMENT AS YOU GO

Some first-time applicants wait until very late in the process to begin creating the IND application. You should write up each of the milestones required on the application as you complete them, instead of being forced belatedly to put together what is usually a voluminous document. The documentation will be fresh and you will have time to make sure that it is scientifically sound, addresses a medical need, and has a safety profile appropriate for the clinical indication. If your organization does not have prior experience with writing INDs, hire a professional contractor who understands the types of issues that the FDA often raises. This will be money well spent, because your IND document will be professionally prepared according to FDA expectations.


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