We have all experienced them: those moments when all you can say is, “Oh, No!” or perhaps, “Oh $%&@!” Such moments happen in the development lifecycle of a drug or device all too often. What you do and say next can have huge impact on your product. So, what actions do you take? What can you say? This blog entry is the first in a three-part series intended to provide some guidance.

We’ll take a look at four “Oh, $%&@!” situations that commonly occur when interacting with regulators and examine the best approach to dealing with them. We will assess the situations by order of increasing difficulty:

1. Handling questions generated in response to a regulatory submission
2. The FDA inspectors have arrived at your facility
3. Receiving and responding to FDA 483s
4. Warning Letters

Answering questions from regulators regarding your regulatory submission

“A key step in preparing any regulatory submission is to anticipate possible questions that you may receive and strategize how you will respond.”

You have sent your submission off to regulators. And now, they have questions for you. For drugs, these tend to come in the form of emails from the Project Manager to the person you identified as your contact when you sent in the submission. They will typically say something like, “In order to complete the review of your submission in a timely fashion we will need answers to the following questions.” Then, they will give you a deadline. For marketing applications (NDAs, BLAs), you may be granted a wide response window, anything from 24 hours to two weeks to respond. For clinical submissions (INDs, IDEs, IMPDs) you will likely have only a very short time to answer, typically a day or two, at most about a week.

For device submissions, the communication comes from the reviewer. Communications may come via email in the form of an Interactive Review, to which you can respond in the same way. Alternatively, you may receive a Major Deficiency letter, putting your application on Hold until the outstanding issues are resolved. Response times for Interactive Review questions tend to be short, while you typically have 180 days to respond to a Major Deficiency Letter. However, since the latter results in a hold on your application, preparing and submitting responses as quickly as possible will be important.

Anticipating the questions that regulators may pose

So, what do you do when you receive questions? Ideally, any questions you receive do not come as a surprise. A key step in preparing any regulatory submission is to anticipate possible questions that you may receive and strategize how you will respond. I emphasize the importance of this step as I work with clients to prepare their submissions. It has several benefits. First, when you think of a potential question before submitting your application, you can modify your submission to provide information, or make your argument clearer or stronger and avoid the question altogether. Alternatively, you may decide to wait and see if regulators raise a particular issue and the specific manner in which they do so. Then, with the exact wording of the question in hand, you identify the person or persons on your team with the technical knowledge to respond.

But what if you do receive a surprising question? Stop. Take a deep breath and read the question over several times. Pull in the technical members of your team. Identify exactly what information the regulators are requesting. Ask yourself: Why are they asking us about this? The answer will go a long way to ensuring that your response actually addresses the concern that caused regulators to ask the question. Once your team has prepared the response, compare it against the question one more time and ask yourselves, “Does this answer what the regulators are asking?”

What do you do if you receive a lot of questions? I mean a lot of questions. I have seen regulators send lists of dozens of questions, each with several sub-questions. The approach should not be different than what I described above. Work through the questions with your team, identifying the questions for which you have already prepared responses and prioritizing those that you did not anticipate (there will always be some of those). Next, assign members of your team to each question and provide a timeline for preparing responses. Then, check the responses against the questions to be certain that you are answering what regulators actually asked.

What do you do if you are not sure what it is the regulators want to know? Sometimes, a question will confuse you to the point where you do not know how to begin to address it. In such cases, it is appropriate to contact the project manager or reviewer who sent the question and just tell them, “We will be happy to respond to your question, but first, we need your help to be sure that we understand what is needed here.”

At Pearl Pathways, we partner every day with companies to answer their questions about the path to regulatory approval and to help answer regulators’ questions too. The next blog in this series will deal with what to do when the FDA inspectors show up at your facility. Check back to the Pearl Pathways blog soon to find out.