Quality regulatory submissions to FDA are hard work. A successful NDA or PMA is the result of dedicated teams of people working under stressful conditions. Time-frames can be demanding with anxious investors at one end and the scrutiny of FDA at the other. How do you keep your sanity through it all? Good question. The same formula can be used whether you are working on an IND for a promising candidate or a PMA or NDA for final approval.
We have a Guest Commentary by veteran regulatory consultant Louise Johnson to help provide some clarity.
Ten Things I’ve Learned to Make Regulatory Submissions Effective and Maintain My Sanity At the Same Time
1. Write the Table of Contents (TOC) first. While you may already have a detailed project plan, there is no better way to ensure your submission is complete than to write a detailed TOC. This should be sufficiently detailed to include each individual document.
2. Know the purpose of each document. I once received a draft pharmacokinetic (PK) study report that did not include the PK data! Obviously, this document did not meet its purpose and is an extreme example. Keep in mind that each document makes a unique contribution to the submission. When a document is written without an understanding of its role, the submission may be incomplete and could result in more questions from reviewers.
3. Create submission timelines with the entire team in person.Discussion of detailed timelines allows team members to explain their timing needs and the impact of other team members’ activities on their work. Allowing team members to have input into timelines increases their commitment to reach their goals and to support others reach their goals. If the team finds there is a risk of not meeting corporate goals, that information can be communicated upward to discuss alternative approaches (identifying additional resources, refinement of the goal, etc.). I’ve been on teams that had impossible timelines assigned to them by upper management – nothing kills morale faster than believing you have been put in a position to fail.
4. Define what final means – there is no such thing as a final draft. Believe it or not, final can mean very different things to different people. Some authors think that drafting a document makes it final since they’ve done their part. A regulatory person defines final as a complete, approved document that is ready to be inserted into the submission. Since a fair amount of time can transpire between a draft document and the approved version, make sure the team has a common understanding of when a document is final.
5. Limit the number of draft versions of a document.It can be tempting to add just one more piece of information after a document has been circulated for review. Do not do it! You run the risk of reviewers commenting on different versions, which confuses everyone and increases the chance of errors. Reviewers have limited time and the quality of their review decreases the more times they’ve seen the same document with only minor tweaks between versions. It’s also much more difficult to track 6 drafts than 2 drafts. Spend the time to make each draft as complete and accurate as possible and you will spare yourself the misery of trying to keep track of different sets of comments and different draft documents.
6. Know when to stop editing a document. When a document meets its purpose in the submission, is correct, and is easy to understand, it is complete. When comments or switch back and forth between alternate ways of saying the same thing or are predominantly changes to writing style, you are no longer adding quality to the document.
7. Do it right the first time. In the long run, shortcuts will cost more time than they save. Even something as simple as running a spell check before distributing a document for review makes a big difference. Do you really want highly trained scientists spending their time correcting spelling errors? In extreme cases, a clinical study may need to be repeated if adequate time and thought was not put into the study design. For some small companies, the failure of a clinical study has meant the failure of the company. In most cases, though, you can reduce the number of review cycles for documents, avoid duplication of small studies, and decrease costs if you invest appropriate time at the beginning.
8. Identify team member absences ahead of time. I’ve worked on submissions where a critical team member was needed for a last-minute approval and no one could get in touch with him. We were able to get approval from another manager, but it required time and energy to identify that backup person. Any absences are critical close to the filing date, when the team is scrambling to finish the submission. If you have identified team members who will be absent and have identified their backups at the beginning, you’ll be able to efficiently complete the submission without wasting time and energy looking for people.
9. Know when to take a break.It can be tempting to think that the more you work, the better the submission will be. However, as you tire, your ability to think strategically and creatively decreases. I’ve found I often come up with a solution to a problem after a good night’s sleep. I’ve also quickly found errors from the previous day by getting sufficient rest. In my worst experience, we submitted a briefing package for an Advisory Committee meeting that included a discrepancy in the number of people who died during the clinical development program. The next morning, the error practically leapt off the page at me. While it was easy to correct the error, I would have much preferred to delay the submission by a day and submit an accurate document.
10. Keep a sense of humor.Important submissions can be stressful and it’s possible to see people behaving in less than ideal ways. If you can keep your focus on the big picture and see humor in everyday challenges, you can actually enjoy working closely with the team and develop trust and respect for each other. I worked on one submission that was very important to corporate headquarters; we were asked to provide daily updates. This seemed burdensome because we were so busy, but we decided to send photos of different people working on the submission each day. This made the updates fun for us. Headquarters loved the photos and developed a better understanding of the challenges we faced.
By Louise Johnson
There is more Guest Commentary at the page at the top of the Blog. Read about protocol deviations, CAPA Basics, and informed consent.
The blog, FDA Matters has another interesting post, I now subscribe to weekly updates, on 12 years of exclusivity. He says he “asked Congressional staffers: how many of the Senators and Representatives understand that the follow-on biologics debate is about the amount of data exclusivity, not market exclusivity?”
I certainly didn’t know. Check it out: