Finding the One Decision Here That Removes 100 Decisions
Many of the development activities leading to the filing of an Investigational New Drug Application (IND) are carried out in parallel.
For example, synthesis (small mol)/fermentation and cell culture (biologics), purification, and analytical testing and characterization and formulation are all moving onward at the same time. Sponsors often approach these activities sequentially: run the experiments, develop the process and assays, then prepare and test clinical supplies, saving all writing tasks until last.
But a sequential approach increases the difficulty of preparing an IND and is usually the cause for filing delays, or worse. Based on our familiarity working with smaller emerging biotechs and the FDA, we have found that by adhering to the following principles you can greatly enhance your probability of a timely and successful IND submission.
Ideally, even before the research phase, you should study the relevant FDA regulations/guidances and forms for an IND submission, which can be found on the FDA’s web site (and below), and determine how your organization can best meet those requirements. Companies that devote disciplined, systematic attention from day one move far more efficiently toward opening trials than companies who chose to delay.
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.
The failure to design, execute, and generate the right data from the outset can come back to trouble you and cause unwanted delay. To minimize the preparation time required for the chemistry, manufacturing, and controls (CMC) section of the IND especially, writing and document preparation should also be integrated with the other development activities and coordinated by experienced technical writers and editors.
The documentation will be fresh and most important accurate and you will have time to make sure that it is scientically sound, and addresses a requirement.
Regulatory agencies raise questions if appropriate content items are not present or are inconsistent throughout the documentation and if insufficient details or data are provided on the manufacturing process, sample testing, or container stability.
Unfortunately, when some companies find themselves before the FDA with inadequate data, they go into survival mode and defend the product, arguing that the agency should approve the IND anyway. Doing this runs the risk of losing credibility with the agency on all counts.
Some sponsors 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. 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 proficiently prepared according to FDA expectations.
The following links are relevant to filling an Investigational New Drug application in the US. Quality
Note: this provides excellent instructions if you’ve not led an IND before.