On September 28, 2018, FDA issued draft guidance on contents of a complete submission for threshold analyses and human factors (HF) submissions to drug and biologic applications that remains open for a 60-day comment period. The draft guidance illuminates the proper contents and submission procedures to facilitate efficient FDA review. It applies to human prescription drugs, including biologics, that are the subject of an IND, NDA, BLA, or ANDA, and human nonprescription drugs that are the subject of an IND, NDA, or ANDA.

To ensure that drugs and biologics are safe and effective, FDA reviews each product’s user interface. The user interface is the part of the product that the user interacts with, such as the packaging, labels, and any controls or displays. Threshold analyses compare combined drug products to identify any differences between the combination product itself and the product’s labels, packaging, and controls. By contrast, the various HF submissions study the interaction between the user and the user interface to determine if the product is used properly and any risks associated with improper use.

The draft guidance identifies the following six submissions and offers proper content detail for each: User-Related Risk Analysis, HF Validation Study Protocol, HF Validation Study Results Report, Threshold Analyses, Comparative Use HF Study Protocol, and Comparative Use HF Study Results Report.

While the draft guidance does not comment on exactly when threshold analyses or HF submissions are warranted, it notes that each regulatory pathway will generally require certain submissions. For example, IND sponsors should expect to submit an HF validation study protocol and ANDA sponsors should expect to submit threshold analyses. For Commercial IND, NDA, BLA, or ANDA, sponsors should send their submission in Electronic Common Technical Document format. Submissions connected to a Research IND may be submitted in either electronic or paper format, with at least three copies of the paper submission sent to one of the appropriate addresses listed in the draft guidance.

Finally, the draft guidance spells out the review timeline for complete submissions. For HF validation study protocol submissions, FDA intends to review 50% of the submissions by 2019, 70% by 2020, and 90% by 2021. If a sponsor submits an improper question or response after submitting an HF validation protocol, FDA will consider the protocol submission withdrawn. For threshold analyses and comparative use HF submissions, FDA will use good review management principles and practices to timely review and respond to each submission.