USFDA Guidance: How to Prepare a Pre-Request for Designation (Pre-RFD)

The U.S. Food and Drug Administration (FDA) has released its updated guidance “How to Prepare a Pre-Request for Designation (Pre-RFD)”, issued on November 6, 2025. This guidance provides companies with a clear roadmap for obtaining early, non-binding feedback on the regulatory classification of their products — especially combination products, which often sit at the intersection of drugs, devices and biologics.

The updated guidance strengthens transparency, clarifies expectations and helps sponsors make informed decisions early in development.

1. What the Pre-RFD Guidance Is About

This guidance helps sponsors understand how to prepare and submit a Pre-RFD, which is an informal request to FDA’s Office of Combination Products (OCP).Through a Pre-RFD, companies can ask FDA for preliminary feedback on whether their product will be regulated as a drug, device, biologic or a combination product, and which FDA center (CDER, CDRH or CBER) will take the lead.

The Pre-RFD is not a final decision, but it provides essential direction to help shape development plans, testing strategies and timelines.

2. Importance for Combination Products

Combination products have multiple components — for example a drug paired with a device, or a biologic integrated with a delivery system. Their classification depends on the primary mode of action (PMOA), which can be scientifically complex.

The guidance makes it easier for sponsors to explain how each component contributes to the therapeutic effect.This clarity helps FDA determine the correct regulatory pathway early, reducing uncertainty later in development.

3. Key Highlights of the Guidance

Early, Non-Binding FDA Feedback

A Pre-RFD gives sponsors the chance to understand FDA’s thinking before committing to costly studies or full Requests for Designation (RFDs).

Flexible Timing

Sponsors may submit a Pre-RFD at any stage, as long as they can describe the product, its components and its intended use.

Clear Submission Expectations

The guidance outlines what every Pre-RFD should include:

• A complete product description with images, diagrams or component breakdowns

• Intended use and clear instructions for use

• Ingredient lists or material compositions, including the role of each component

• A scientific explanation of the mechanism of action

• A discussion of why the product may be a combination product

• A description of how the product will be packaged, marketed or used together

These elements help FDA understand how the product works and what drives its therapeutic effect.

Meeting Opportunities

Sponsors can request:

• Informational meetings before submitting a Pre-RFD

• Explanatory meetings after receiving FDA feedback

These meetings support smoother communication and reduce back-and-forth delays.

Review Timelines

FDA aims to:

• Accept the submission within 10 business days

• Provide written feedback within 60 calendar days

Sponsors may withdraw the submission any time before the assessment is issued.

4. Structuring a Strong Pre-RFD

The guidance encourages sponsors to follow the order of the recommended structure to keep submissions clear and easy to review. It also recommends keeping the main document to 15–20 pages, using simple formatting and limiting appendices to only what is needed to explain the product.

The emphasis is on well-supported, scientifically grounded explanations — especially around mechanisms of action — rather than extensive safety or manufacturing data not related to classification.

5. Why This Guidance Matters

This updated guidance gives sponsors a more predictable, transparent and efficient process for engaging with FDA on product classification.For novel technologies and combination products, this early clarity reduces regulatory uncertainty and helps teams design development plans that align with FDA’s expectations from the start.

The guidance reflects FDA’s ongoing commitment to improving communication, supporting innovation and ensuring that products follow the correct regulatory pathway throughout their lifecycle.

FDA’s 2025 update to the guidance strengthens the agency’s approach to early product classification. By clarifying expectations, improving meeting pathways and focusing on the complexities of combination products, the guidance helps manufacturers move through development with greater confidence.

For more details, please refer to the "How to Prepare a Pre-Request for Designation (Pre-RFD)" guidance provided by the U.S. FDA.