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

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Introduction

The FDA’s guidance “How to Prepare a Pre-Request for Designation (Pre-RFD)” provides structured recommendations for sponsors seeking preliminary feedback from the Office of Combination Products (OCP) on how their product should be classified (drug, device, biologic, or combination product) and to which FDA centre (e.g.,
Although this is a U.S. FDA document, its lessons and structure are of interest to global regulatory professionals, including MAHs in other jurisdictions, because it clarifies how regulatory authorities think about classification and regulatory pathways.

For MAHs (Marketing Authorization Holders) and other stakeholders (manufacturers, sponsors, regulatory affairs teams, combination-product developers) this guidance is relevant because:

  • It sets out best practices for interacting with an authority like the FDA when classification/centre assignment is unclear.
  • It helps manage the regulatory risk of mis-classification (which can cost time, money, and lead to regulatory delays or re-work).
  • For combination products especially, it shows what information the regulator expects with respect to constituent parts, primary mode of action (PMOA), marketing strategy, etc.
  • Even for purely drug or purely device products, if there is novelty or ambiguity, the Pre-RFD route is a helpful tool.

In what follows I summarise the key points of the guidance, then go deeper into implications for MAHs, practical checklists, issues to watch, and recommended next steps.

Key Elements of the Guidance

Below are the major sections of the guidance and their contents, with commentary.

Background (Section II)

  • The OCP has served since December 24, 2002 as the unit within FDA to help determine classification and centre assignment of medical products. U.S. Food and Drug Administration
  • The guidance explains that a sponsor may either submit a formal Request for Designation (RFD) under 21 CFR Part 3 (which results in a binding decision) or use the Pre-RFD process (which is informal, non-binding) to get preliminary feedback. U.S. Food and Drug Administration
  • The Pre-RFD process is intended to enhance transparency, consistency and efficiency by clarifying expectations for sponsors. U.S. Food and Drug Administration

What is a Pre-RFD? (Section III.A)

  • Defined as “a clear and concise written submission that a sponsor may make to OCP to request FDA’s preliminary, non-binding assessment of their product’s classification and/or center assignment.” U.S. Food and Drug Administration
  • The feedback is non-binding: the sponsor can still submit an RFD later, or proceed with the appropriate centre/sponsor path. U.S. Food and Drug Administration
  • It is available for either non-combination products (i.e., a drug alone, device alone, biologic alone) or combination products where classification or assignment is unclear. U.S. Food and Drug Administration

When should a Pre-RFD be submitted? (Section III.B)

  • The guidance states it may be submitted at any point during medical product development, but the ability of OCP to respond depends on whether sufficient information has been provided. U.S. Food and Drug Administration
  • However, the guidance warns that if the technology/concept is not sufficiently defined (i.e., no defined composition, proposed use, indication) then a Pre-RFD may not be appropriate. U.S. Food and Drug Administration

Meeting requests with OCP (Section III.C)

  • Sponsors may request an informational meeting (prior to submission) or an explanatory meeting (after the Pre-RFD response) with OCP. U.S. Food and Drug Administration
  • The guidance provides details on how to request the meeting, format (teleconference, virtual, in-person), and meeting package requirements. U.S. Food and Drug Administration
  • Timing targets: OCP generally aims to hold an informational meeting within ~6 weeks after receipt of a complete package. U.S. Food and Drug Administration

Submission and review of Pre-RFD (Section III.D & III.E)

What to include (Section IV)

This is arguably the core of the guidance for sponsors. The document outlines the basic and recommended information for submission:

A. Basic Information

Key items include:

  1. Sponsor’s name and contact details (including authorised representative if applicable). U.S. Food and Drug Administration
  2. Complete description of the product: name, regulatory submission number (if applicable), marketing history, etc. U.S. Food and Drug Administration
  3. Proposed use/intended use/indication for the product. U.S. Food and Drug Administration
  4. Instructions for use/conditions of use. U.S. Food and Drug Administration
  5. Listing of all components (active and inactive), including materials, concentrations, purpose of each component. U.S. Food and Drug Administration
  6. If biologically-derived materials are included: detailed description of processing, source, characterization. U.S. Food and Drug Administration
  7. Explanation of how the product works (mechanism of action) and basis for that explanation (studies, data). U.S. Food and Drug Administration
  8. For combination products: information on relative contributions of constituent parts to the overall therapeutic/diagnostic effect (i.e., primary mode of action) and supporting tests/studies. U.S. Food and Drug Administration
  9. Explanation of how the product will be marketed: whether components are separately marketed, co-packaged, physically combined, etc. U.S. Food and Drug Administration

B. Format

Additional/Other Considerations

  • The guidance reminds sponsors that OCP’s assessment is non-binding. If the product changes significantly (e.g., indication, ingredients, manufacturing) after Pre-RFD feedback, the feedback may no longer apply. U.S. Food and Drug Administration
  • Guidance also includes the paperwork burden estimate under the Paperwork Reduction Act. U.S. Food and Drug Administration
  • History section: This document replaces the February 2018 version and is the “Level 2 Final Guidance” (November 2025). U.S. Food and Drug Administration

Implications for MAHs and Other Stakeholders

While this is a U.S.-FDA guidance, many MAHs (Marketing Authorization Holders) and regulators in other jurisdictions can derive value from the structure and principles. Below are key implications, challenges, and “what to keep in mind” for MAHs, regulatory affairs professionals, manufacturers and combination product sponsors.

For MAHs (Marketing Authorization Holders)

If you are an MAH (or will be) for a product that may have classification ambiguity (e.g., drug-device combination, biologic-device combination, novel modality) then the following are important:

  1. Know whether classification is clear: Many products have well-understood regulatory pathways (e.g., a generic small-molecule drug, a standard medical device). But if your product has novel mechanism, or combines device + drug, or uses new materials, then classification/centre-assignment risk is real. The Pre-RFD process is designed for such scenarios.
    • If you wrongly assume your product is a device when the regulator sees it as a drug (or vice-versa), you may choose incorrect submission route, face delays, additional data requests, or even re-work.
    • Thus, for a product under development, early engagement (e.g., via Pre-RFD) can save time and cost.
  2. Inclusion in early regulatory strategy: As an MAH you should incorporate classification/centre-assignment assessment into your regulatory planning. When drafting dossiers, interacting with regulatory authorities or preparing filings, you need to know:
    • Which centre/regulator you will deal with (in FDA’s case, CDER, CDRH, or CBER).
    • Which regulatory pathway applies (e.g., NDA, ANDA, 510(k), PMA, BLA, etc).
    • If combination product: who is primary centre, what additional device regulation applies, what device standards/testing apply, etc.
    The guidance places emphasis on providing mechanism-of-action, component contributions, marketing plan (components separately/combined) etc. This is helpful for regulatory strategy under your umbrella as MAH.
  3. Document management & internal alignment: The guidance sets out what information to include and how to format. For MAHs this means:
    • Ensure all internal documentation (product description, components, materials, indications, marketing plan) is consistent and ready for submission.
    • If you later change composition, indication or manufacturing, you must note that the Pre-RFD feedback may not apply, so you need to re-assess. (Good internal change-control practice).
    • Records: The Pre-RFD response from FDA should be filed, and used when interacting with FDA or when submitting formal regulatory filings. The guidance recommends sending the Pre-RFD response to the appropriate Centre. U.S. Food and Drug Administration
  4. Global regulatory alignment: Although the guidance is FDA-specific, many jurisdictions follow similar logic for combination products or ambiguous classification. MAHs operating globally should:
    • Map whether classification ambiguity exists in each jurisdiction (India, EU, etc).
    • Use the structure of Pre-RFD (or equivalent) as checklist for what information to gather early.
    • Internal regulatory affairs teams should benchmark processes: e.g., component list, mechanism of action, marketing plan, etc.
  5. Risk mitigation: Engaging early and ensuring classification/centre assignment is resolved is a risk mitigation measure. If you wait until later (e.g., just before submission) and classification is contested, you may face delays, rework, uncertainty, and added cost.
  6. Change management: As mentioned, if product changes significantly after the Pre-RFD, the earlier feedback may no longer apply. MAHs should maintain a change-control log indicating any substantial changes to indication, composition, manufacturing, etc and assess whether re-submission or updated engagement with regulator is needed.

For Combination Product Sponsors

Sponsors developing combination products (i.e., products comprised of two or more regulated components such as drug + device, or device + biologic) have additional complexity. This guidance is particularly relevant for them.

Key points:

  • The guidance emphasises the importance of identifying the Primary Mode of Action (PMOA) of the combination product to determine which centre will have primary jurisdiction. U.S. Food and Drug Administration
  • You must provide information on the relative contributions of constituent parts to the therapeutic/diagnostic effect. U.S. Food and Drug Administration
  • The marketing strategy matters: Are components separately marketed? Are they co-packaged? Are they physically or chemically combined? These distinctions affect classification and regulatory pathway. U.S. Food and Drug Administration
  • For combination product sponsors, preparing a good Pre-RFD can help clarify regulatory expectations, reduce surprises, and align internal development plans (clinical, manufacturing, regulatory) accordingly.

For Regulatory Affairs Teams & Consultants

For professionals in regulatory affairs (including those consulting pharmaceutical/medical device companies, such as yourself), this guidance provides a structured framework you can adapt for your clients:

  • Use the checklist in Section IV as a template for client submissions or internal dossier planning.
  • Where classification or centre assignment is unclear, recommending a Pre-RFD (or equivalent in jurisdiction) is a prudent approach.
  • Be ready to advise on meeting strategy (informational/explanatory) with regulator, preparation of meeting package, timing, etc.
  • Integrate this with global regulatory strategy by comparing how other jurisdictions handle classification/combination products.
  • For clients with product change events (e.g., manufacturing change, new indication, combination product upgrade), advise re-assessing classification/centre assignment and perhaps re-engaging regulators.

Other Stakeholders: Manufacturers, R&D, Clinical Teams

For manufacturing, R&D, clinical development teams, the guidance reminds us that classification/centre assignment affects:

  • The type of regulatory submissions required (e.g., device standards, device testing, human factors, biocompatibility, etc).
  • The type of clinical trials or non-clinical testing needed. For example, a device-dominated combination likely has device-type testing; drug-dominated might follow drug type trials.
  • Manufacturing requirements, documentation, component testing (especially for biologic materials or device materials).
  • Labeling, instructions for use, marketing claims—all tied to how the product is classified.

Practical “What to Keep” Checklist for MAHs and Sponsors

Here is a practical checklist based on the guidance, tailored for MAHs/sponsors, to use internally. This can help ensure you are prepared for classification/centre-assignment considerations.

Pre-Submission Stage

  • Confirm if classification and/or centre assignment is unambiguous. If unclear → consider Pre-RFD (or equivalent).
  • Gather sponsor contact details (name, address, authorised representative, email, phone).
  • Prepare full product description: product name, regulatory submission numbers (if any), marketing history.
  • Prepare proposed use/intended use/indication for the product.
  • Prepare instructions for use/conditions of use.
  • For each component (active & inactive): list name, source, composition (materials, concentrations), purpose of inclusion.
  • If biologically-derived materials: record source, processing steps, characterization of material.
  • Prepare mechanism of action explanation: how product works, how each component contributes (especially for combination products). Include study data/supporting information.
  • For combination products: map out constituent parts, marketing plan (are components separately marketed, co-packaged, physically/chemically combined?), and relative contributions.
  • Prepare diagrams/photos of the product (device images, co-packaging layouts, component schematics).
  • Prepare short, focused background document—non-redundant, clearly written.
  • Ensure internal alignment: R&D, manufacturing, regulatory affairs, marketing are consistent in description of the product.
  • Plan for meeting strategy with regulator (informational or explanatory), prepare meeting package and suggestions for timing.
  • Understand potential ‘change’ risk: document how changes post-feedback might impact classification/centre assignment.

Submission Stage

Post-Feedback Stage

  • Review the feedback letter/response: note the classification/centre assignment decision and rationale. U.S. Food and Drug Administration
  • File the feedback with your regulatory dossier and ensure it is referenced in subsequent communications with the regulatory centre. U.S. Food and Drug Administration
  • If you disagree with feedback: plan to request explanatory meeting or submit a new Pre-RFD with additional information. U.S. Food and Drug Administration
  • Monitor for internal changes: if the product’s composition, indication, manufacturing process, or marketing plan changes significantly, evaluate whether the Pre-RFD feedback remains applicable or whether you need to re-engage. U.S. Food and Drug Administration
  • Integrate classification/centre assignment into your regulatory submission planning, manufacturing strategy, clinical development plan, labeling/marketing claims.

Key Challenges & Pitfalls to Watch

Here are some “gotchas” and potential pitfalls that MAHs and sponsors should be aware of, based on the guidance and my regulatory-consulting experience.

  • Insufficient early information: The guidance emphasises that if the product is still at too early a concept stage (no defined composition, indication) the Pre-RFD may not be appropriate. U.S. Food and Drug Administration Sponsors who rush to submit without clear information may get requests for additional info, delays, or less useful feedback.
  • Over-complex or unfocused submissions: The guidance warns that large volumes of extraneous data may slow the review. Conciseness and clarity help. U.S. Food and Drug Administration
  • Changes after feedback: If you receive feedback then later change key product attributes (indication, composition, manufacturing, marketing plan) the feedback may no longer apply. This can cause misalignment or necessitate re-work. U.S. Food and Drug Administration
  • Marketing vs regulatory disconnect: The way you plan to market the product (co-packaged vs separately marketed) influences classification/centre assignment. If marketing strategy is changed after Pre-RFD, you must reassess.
  • Global vs U.S. regulatory divergence: While the FDA guidance is U.S.-specific, other jurisdictions may have different definitions or regulatory approaches (for combination products, drug vs device) so you cannot assume perfect equivalence. Make sure to carry out regional/regulatory-jurisdictional mapping.
  • Internal misalignment across functions: If R&D, manufacturing, labeling, marketing, regulatory are not aligned on product description, component list, mechanism of action etc, you may receive inconsistent responses or face issues later.
  • Timing: Waiting too late to engage with classification/centre assignment questions can lead to regulatory delays, especially for novel or ambiguous products. Early engagement is advisable.
  • Regulator’s non-binding feedback: Remember the Pre-RFD is non-binding (in the FDA context). Hence, while it is useful, it does not guarantee the final regulatory outcome. Prepare your internal strategy accordingly.

Strategic Recommendations for MAHs & Regulatory Teams

Based on the above analysis, here are strategic recommendations:

  1. Build classification/centre assignment assessment into your product development timeline—especially for novel or combination products. Don’t leave it until submission time.
  2. Use the guidance’s checklist to prepare your internal dossier early (component list, mechanism of action, marketing plan, diagrams/photos). This will improve efficiency and regulatory clarity.
  3. Engage with regulator early: Use an informational meeting if helpful (before submitting Pre-RFD) and plan for an explanatory meeting if you receive feedback and have questions.
  4. Ensure cross-functional alignment: R&D, manufacturing, regulatory, marketing must speak the same language about the product (composition, indication, marketing plan). Misalignment increases risk.
  5. Monitor for changes: Maintain change control over major product attributes (indication, composition, manufacturing, marketing) and assess if re-submission/updated engagement is needed.
  6. Document everything: The Pre-RFD response should be retained in your regulatory archive and referenced in future communications/submissions.
  7. Map global implications: While this FDA guidance is U.S.-specific, you should compare how your product would be classified/regulated in other jurisdictions (India, EU, etc). Use the structured approach to ask equivalent questions locally.
  8. Budget time and resources: Because classification/centre assignment impacts regulatory pathway, you may need additional testing (especially for device components) or documentation. Plan this into your budget and timeline.
  9. Be conservative about marketing claims: If classification is unclear, avoid marketing strategy that could trigger additional regulatory oversight (for example, device claims when you expect drug pathway).
  10. Use the Pre-RFD feedback to inform your formal submission strategy: Although non-binding, the feedback helps you choose the correct regulatory path, centre, and submission type (e.g., NDA vs PMA) and allows you to better prepare your regulatory submission.

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