No one wants a regulatory question. We try to ensure our regulatory submissions are completed with high quality and in line with guidelines. We try to anticipate reviewer concerns. We try our best to provide a comprehensive submission document but who can account for different perspectives on review? Sometimes questions come back after a submission is made. There is no choice but to deal with the responses quickly. Moreover, we must respond so that we don’t generate more questions. The rest of the team is watching, CMC can't torpedo the timeline.
Ok, let's get to it: First, let's assign a Response Leader. Who is that? It should be someone who has an in depth knowledge of the project (a key stakeholder), who is clear thinking, can manage timelines, and is senior enough to make decisions. She/he understands the risk vs reward. Then, let's read through the full document with the key team players and anyone whose perspective could be helpful in the room (or zoom room as the case may be). Let's discuss each question from the point of view of the Reviewer. We'll listen to everyone's point of view. This is when we need to be the most collaborative and focussed.
Next, we will assign each question to a team member. The responders will have the most knowledge of the issue and can find the data quickly. We'll set a deadline of no longer than 24 hours to draft a response. Each responder will break off with additional people as necessary to craft their answer in a smaller, more focussed team. Key here is to communicate with service providers or CMO's whose work is involved. Suppliers need to be made aware, right away. Their input, whether it be additional data or experience in answering similar questions, can be critical. Once the drafts are done, even if not perfect yet, we get them over to the person collating the response and the rest of the team. The drafts, however raw they may be, will get the ball rolling and the thinking moving. We'll set a time to meet again in 24hours or less. We’ll look at the other responses when ours are done to be ready to discuss and add input in the next meeting.
The Response Leader or a regulatory team member collates the draft responses on a response template to keep the style the same. It is critical to indicate the full question above each response and number the questions. Then to ensure each response is exactly what the Reviewer is asking for, we repeat the question as the introduction to the response. The repeated wording is done in a manner that leads right into the beginning of the answer. This repetition of the question really focusses the answers and, most importantly, ensures the question is understood and fully responded to.
In the second meeting, we'll all get a chance to go line by line, led by the Response Leader, to discuss the answers. More brainstorming happens to complete the drafts. We agree to a finished product or generate additional data requests. Once again, individuals are assigned to complete the updated drafts. This time, each are given a very a short deadline (hours), commensurate with that short window given by the Regulatory Agency. We look at the question, we read it back as we answer the question and we ensure all of question is dealt with.
In the final stages of the response, the Response Leader, and the key senior stakeholder (if they are different) work together with CMC Regulatory to painstakingly review each question and response. We must pull the reponses together in a way that makes the document succinct and on point without extraneous information. Each response cannot result in further questioning. This takes real skill and intimate knowledge of the project and this step may end up in one or more all-nighters. We do that if we have to. We read, re-read, think like a reviewer, read, re-read again over as many cycles as it takes to get this document tight.
We do a QA review of any data or key facts within the document. We ensure that all stakeholders sign-off before CMC Regulatory takes the document and moves to the final step. Boom, response filed. Fingers crossed. Well, not necessarily because you read and re-read, checked the response against the question and thought and read and re-read and thought and gave it your best and then you pushed the ball across the finish line. Phew!