Many people working in drug development have expressed the frustrated wish that regulators would just go ahead and tell them exactly what they must do in order to move their drug through the development and approval process. The level of exasperation with the regulatory process is understandable. But the fact is, many of the questions that get routinely asked, have already been answered, by FDA and other regulatory bodies. The key is knowing where to look.
For example, the FDA has put out a large number of guidances on everything from how to evaluate the effectiveness of a drug for treating acne, to what to include in an IND submission. The FDA’s Guidance Page is a treasure trove of written guidance on all sorts of drug development topics.
It is important to remember just what an FDA Guidance actually means and how it fits into the overall regulatory landscape. The base of the regulatory pyramid is the Food, Drug, and Cosmetic Act as amended. The FD&C Act is the law. It tells you what must be done. Since there are so many possible scenarios, the Act is, out of necessity, broad and general. It will tell you that you must file an Investigational New Drug application (IND) in order to test your drug in humans, but it won’t tell you how to do that in any detail. The next level of the regulatory pyramid is the Code of Federal Regulations (CFR). In Title 21 of the CFR is found an extensive list of regulations which covers Food, drugs, biologics, and medical devices. Regulations are more specific than the FD&C Act, but you still won’t find the detailed step by step list of regulatory expectations here. Both regulations and the FD&C Act use language like must or shall, clearly indicating that they are requirements.
Guidances, on the other hand, represent recommendations as I have written here in an earlier blog post. Every guidance document FDA publishes has the following disclaimer, “Guidance documents represent FDA’s current thinking on a topic. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.” In practice, this means that if you follow the recommendations of the guidance, the FDA is very likely to accept your approach. In the unlikely event that they do not, the onus is on the FDA to explain why your situation is special and not covered by the guidance. The other thing to be aware of is that guidances represent a snapshot in time. Knowledge increases, current best practices change and, if the guidance is not recent, it may provide somewhat out of date recommendations. Regardless, it is the guidances that you will find detailed information of what regulators expect to see from you.
And that, of course, is why you should consider meeting with FDA to share your plans and get their buy-in, whether you are following the guidance exactly or are taking an alternative approach. Even the most up to date guidance still can’t address every possible situation. I have written before about meeting with FDA and how to ask FDA questions. So where do you start? Here is the path that I would recommend:
- Check to see if FDA has published a guidance on the medical condition or topic about which you have questions. Knowing what endpoints the Agency expects to see in a clinical trial is of enormous value.
- Take a careful look at guidances on what to include in IND submissions, whether the initial Phase 1 study or amendments to allow for Phase 2 or Phase 3 clinical trials.
- Seriously consider meeting with FDA to raise questions about your planned approaches in the areas of clinical trial design, chemistry, manufacturing, and controls, and pre-clinical animal studies.
It turns out that the FDA has gone a long way to telling you exactly what hoops they expect you to jump through—it’s just a matter of finding the information, understanding it, and putting it into action in your drug development program. That’s where Pearl Pathways comes in, we have the experience and know how to serve as your guide locating the hoops and, more importantly, getting past them. Contact us today to discuss your drug development plan.