Information Requests and Deficiency Letters: Answering Well

FDA's questions during review range from an informal reviewer request to a formal letter. Once the file is in, the answers are one of the few things a sponsor can still change about the outcome.

Types of request

Information Request (IR). The everyday one. A reviewer needs a clarification, a reanalysis, or a document you did not include. Often informal, often with a short response window measured in days or weeks.

Discipline Review Letter (DRL). Conveys deficiencies from one review discipline before the overall review is complete, so you can begin addressing them.

Complete Response Letter (CRL). FDA's decision not to approve the application in its present form, with different consequences, covered in the CRL entry.

For devices, the equivalent during a 510(k) or PMA review is an Additional Information (AI) request, and it stops the review clock until you respond.

Effect on the review clock

For device submissions an AI request places the file on hold. The review clock stops, and you have a defined period, commonly 180 days, to respond before the submission is considered withdrawn. Time on hold does not count against FDA's review goal.

For drug applications, a major amendment in response to a request can extend the goal date by three months. Weigh that before deciding how much new data to include.

Answering well

Answer the question asked. A response that reframes the question to one you would rather answer reads as evasion and produces a second request.

Answer completely the first time. A partial answer buys another round. Each round is elapsed time on a review clock and another reviewer context switch.

Do not volunteer new problems. Unrequested analyses that raise fresh questions lengthen review.

Be consistent with the file. The answer has to agree with what is already in the application. Where it does not, say so explicitly and explain, because a reviewer noticing the discrepancy themselves is much worse.

Say when you disagree, with data. A reviewer's premise can be wrong, and saying so with evidence is legitimate. Silence reads as agreement.

Before answering

Read the question against your own file first. Frequently the answer is already in the submission and the real problem is that it was hard to find, in which case the response is a pointer plus a clearer presentation rather than new work.

Where the answer is not in the file, the same gap probably exists elsewhere in the submission.