You made it! The commercial team finally agreed to the proposed draft labeling, the regulatory operations team graciously accepted those last-minute changes, and FDA acknowledged receipt of the marketing application through the Electronic Submissions Gateway (ESG). Two months later, FDA accepted the application for filing, which may or may not have been packed with information requests; we hope the latter. Time to take a vacation while FDA begins their review…not exactly. Then you receive an email from the regulatory project manager asking for a new treatment-emergent adverse event (TEAE) analysis…

Responding to information requests (IRs) from FDA during review of a marketing application can be stressful. The requests arrive without warning, and the timelines rarely leave time to breathe. How do you survive the rollercoaster of requests? Outlined below are useful tips and best practices for managing responses to IRs during FDA review of your marketing application.

Rapid Response Team (RRT):  Key to responding to requests quickly is proactively identifying the team that will address any questions from FDA.  Who is the lead for each discipline?  Are any necessary contracts in place if vendors are providing subject matter expertise or completing the analyses?  The best-case scenario is to rely on those who contributed to the original submission.  They are the most familiar with the dossier and datasets.  If that is not possible, ensure any new team members have access to the submitted application and supportive information BEFORE the requests begin.  This allows time to review the information prior to needing a deep dive with a quick turnaround for response.  In any case, all members of the RRT should have access to Word (.docx) versions of the submitted documents.

              Rapid Response Team Members

Leadership: Who will organize the RRT? A person familiar with the dossier should act as the conductor for the RRT, facilitating communication, setting a timeline, and identifying the appropriate RRT members for each request. This individual can use their knowledge of the submission to locate the appropriate source documents and curate the response strategy. The leader should also have knowledge of the publishing and submission process to inform development of the timeline for the response.

Communication: As soon as an IR is received, alert the appropriate RRT members. Is the request straight forward? Email communication between the RRT members may be appropriate. Depending on the request, clarification from the FDA regulatory project manager may be needed. Does the request require discussion amongst the RRT to strategize on the best way to approach the question? Is the requested response time feasible? Schedule a meeting with the necessary team members to align on a response strategy and timeline. A teleconference can lead to consensus more quickly than a never-ending chain of emails. Assign action items to specific people and confirm when a draft response will be ready for review by the team. (Hint: not at 5:00 pm on the day the response is due.)

Organization: Create a space where all IRs and their responses can be saved. A draft response template will make it easier to plug in the information instead of starting from scratch each time. Utilizing a document collaboration platform facilitates version control and allows for expedited authoring and reviews as all appropriate RRT members can work in the document at the same time. For ease of reference, each IR should have its own organizational home (bonus: number these so they sort chronologically) where the original request is saved as well as any draft responses. Including the submission number and date for the formal response will help when IR#20 refers to the table in the SN0018 response that does not match the table in SN0015. Maintaining a correspondence log specific to FDA correspondence pertaining to the review of the marketing application can be a quick reference and will help keep the responses organized.

Response Flow Diagram

And that’s it!  Effectively responding to IRs during FDA review of a marketing application is essentially project management skills on steroids: identify your team early, communicate, and stay organized. As the IRs shift to topics that clearly inform labeling, the light at the end of the tunnel gets brighter, and before you know it the next email is an approval letter, pending no hiccups.

Need help? Rho is highly experienced in preparing marketing applications and supporting regulatory agency review, including rapid responses to IRs, both on the project management side as well as providing subject matter expertise (eg, nonclinical, clinical including clinical pharmacology, CMC) extending to biometrics support. We also support the publishing and submission of files to the FDA and other regulatory authorities. Contact us for more information.

Lauren E. St. Louis, PhD, Regulatory Scientist, has over 8 years of experience writing and editing scientific documents and publications across a variety of chemistry, scientific, and regulatory fields. At Rho, she leads and manages multidisciplinary teams as well as authoring documents to support various regulatory submissions including INDs, NDAs, BLAs, PIPs, briefing packages to support regulatory meetings (Type B/C/D and European scientific advice), clinical study reports and protocols, and other regulatory documents.