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
Conrad J. Heilman, Jr.,PhD
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.