You have just been told by a regulatory consultant or trusted advisor that you have to perform a particular study to get your drug or device clinical trial or marketing application approved. And then you ask yourself, “Where does it say that I have to do that?” As we’ll see, you probably should start by asking the person who told you.
Developing drugs and devices is difficult. Most likely, you will encounter a number of gray areas as you move from an idea to an approved marketing application.
Without the right answers, you can easily spend time and money doing work just because someone told you that it was required when it turns out that the FDA may not accept it as supportive of the goal. So, how do you deal with what I like to call “hearsay requirements”?
There is a simple question that you should ask anyone who tells you that you must to do this or that study to meet FDA expectations: Where does it say in the law, the regulations, or the guidance, that this study is necessary?
Where does it say in the law, the regulations, or the guidance, that this study is necessary?
There are three levels of information related to FDA expectations:
1. The laws. Such laws include the Federal Food, Drug, and Cosmetic Act which states requirements for drugs and devices, and the Public Health Service Act which covers biologics (drugs, usually large molecules, derived from living organisms). These laws give FDA authority but are short on specifics.
2. The regulations. Title 21 of the Code of Federal Regulations (CFR) spells out in some detail the “What” aspects of development. The regulations explicitly state the things that you as a drug or device developer must do. Here are some highlights:
Part 11: Electronic records and signatures
Part 56: Institutional review boards
Part 211: Good manufacturing practice for finished pharmaceuticals
Part 312: Investigational new drug application
Part 314: Applications for FDA approval to market a new drug
Part 316: Orphan Drugs
Part 600: Biological products: general
Part 601: Licensing
Part 812: Investigational device exemptions
Part 814: Premarket approval of medical devices
3. The guidances. These represent the FDA’s current best scientific thinking. Guidances focus on the “How” of development. However, guidances are recommendations, and if you can provide solid scientific justification of an alternate approach, the FDA may accept it. There are guidances on a variety of topics including how to have a meeting with the FDA, detailed recommendations for research in specific disease states, detailed recommendations for specific kinds of devices, and more. Chances are, one of the guidances contains the answers to yoquestions.
So, when someone tells you that you must perform this or that study to meet FDA expectations, turn first to the FDA Guidance page. See if your question has already been addressed in the guidance. If not, then it is time to consider requesting a meeting with the Agency. I have already written about how to ask questions of FDA in the context of a formal meeting.
So, how do people get their wires crossed when giving you advice about FDA requirements? There are likely two main reasons:
1. People tend to provide the most conservative answer when asked about FDA requirements because they don’t want to be wrong.
2. You may receive advice based on someone’s experience with a drug or device for a different indication. FDA’s expectations are more flexible with oncology submissions, for example, because the patients in question often have no good options currently available. For a drug aimed at an indication for which there are already several useful treatments, the bar is higher. You need to consider what your drug or device offers relative to the current standard of care.
Posing this question directly to FDA
You may be wondering if this question works with FDA reviewers. If asked politely, it is perfectly reasonable to inquire about the written authority behind a particular requirement. Prior to working as a consultant, I served as an FDA reviewer, and yes, this question did work with me. In fact, on one occasion the Sponsor pointed out the exact section within a guidance which stated that they did not have to complete the study being discussed. I had to agree. It didn’t annoy me, because they were polite about it and, besides, you can’t know everything.
The earlier you look at your development program and identify what you need to know and understand about the development pathway in terms of regulatory expectations, the more likely it is that you will be able to obtain useful answers. Answers to your questions will be found within the written laws, regulations, and guidances. Alternatively, the answers you seek will be found by posing the right question to regulators. Pearl Pathways regularly communicates directly with FDA on behalf of our clients to obtain answers to the biggest questions impacting their drug or device development timelines. Contact us today for a free 30-minute consultation with your team to ensure you are on the right track.