Welcome back to our blog series on navigating the intricate regulatory landscape of bringing your innovation to market. In Part 1, we explored the distinctions between a medical device and a drug, the classification of which may be challenging to define for some products. Now, we turn our attention to a crucial tool that Sponsors may use to have the FDA classify your product: the Request for Designation (RFD). In this installment, we’ll describe what an RFD entails and its significance in the regulatory realm, providing a comprehensive overview of the process.

An RFD is a formal submission made to the FDA to seek a determination or clarification on how a product will be categorized in terms of regulatory oversight.  While an RFD is not required for all products, you should consider submitting an RFD if your product’s classification is in dispute or unclear, and the submission should occur prior to filing any investigational or marketing application for the product. An RFD is submitted to the Office of Combination Products (OCP), which determines whether the product is a device, drug, biologic, or some combination thereof and, therefore, determines the FDA Center with jurisdiction for the product. Importantly, FDA’s formal response to an RFD is a binding determination on the classification of a product.

Before you submit an RFD for your product, you should ensure you have sufficient information for FDA to be able to decide on the appropriate assignment of your product. Your submission will include the following:

• name of the product
• its chemical, physical, or biological composition
• a description of the manufacturing process
• a brief review of the developmental work, including in vitro and in vivo nonclinical testing that is completed, ongoing, or planned
• a proposed use or indication of the product
• the proposed dosing schedule and route of administration.

The cornerstone of the RFD submission is the discussion on the primary mode of action (PMOA), which defines the classification of device versus drug. As a reminder from the previous blog in this series, drugs act via a chemical or pharmacological action within the body whereas devices use mechanical or technological mechanisms to elicit their therapeutic effect.

If your product employs multiple modes of action, you should describe each in your RFD and identify which is the PMOA, or the mode of action your product employs to provide the most important therapeutic action of the product. It is crucial to include as much test data as possible to support your PMOA designation. More details on the contents of a complete RFD can be found in the FDA guidance entitled Guidance for Industry. How to Write a Request for Designation (RFD) (April 2011).

Importantly, an RFD is limited to 15 pages in total. This constraint presents a challenge for Sponsors, as they must effectively convey all the above information as well as a comprehensive and compelling rationale for designation within a limited space.

Per regulation (21 CFR 3.8(b)), FDA must make a decision and assign a Center jurisdiction 60 days after submission of the RFD. If a designation letter is not issued within 60 calendar days, the Sponsor’s recommendation will become the designated classification or assignment. Importantly, the letter of designation constitutes an Agency determination and can only be changed by requesting reconsideration of the decision within 15 calendar days of receipt of the letter. Reconsideration requests are limited to 5 pages and cannot contain new information. A new RFD must be submitted if there is additional data to present to OCP.

If a Sponsor is not ready to submit a formal RFD, an alternative is to submit a Pre-RFD. A non‑binding determination will be issued by OCP and provide insight into OCP’s thinking regarding the basis for its determination. The Pre-RFD contains similar content to an RFD but does not require the Sponsor to recommend a classification and provide rationale for the recommendation. Key similarities and differences between the RFD and Pre-RFD can be found in the guidance entitled How to Prepare a Pre-Request for Designation (Pre-RFD) (February 2018). The review process for a Pre‑RFD is the same length (60 days) as an RFD. It is important to note that neither Pre-RFD nor an RFD is required for any product; these are optional opportunities for input from the FDA on a product that the Sponsor is unsure whether CDER, CBER, or CDRH will be the lead for the product’s review. The Pre-RFD feedback could be very useful to the Sponsor to ascertain any issues identified by OCP in a non-binding review and then be able to address any items raised by FDA in a subsequent formal RFD submission, the Investigational New Drug application for a drug or biologic product, or an Investigational Device Exemption submission or the marketing application for a device.

In conclusion, the RFD process determines whether a product is classified as a drug or a device. By submitting an RFD and/or a Pre-RFD, a Sponsor will gain clarity on product classification and lead Center for review. Armed with such information, you will be better informed regarding the regulatory requirements applicable to your product and can ensure moving forward with the appropriate regulatory pathway for your development program.

Have questions about the RFD process? Contact us to speak with one of our Regulatory Experts. 

Sources:

United States Food and Drug Administration. Guidance for Industry. How to Prepare a Pre-Request for Designation (Pre-RFD). February 2018.

United States Food and Drug Administration. Guidance for Industry. How to Write a Request for Designation (RFD). April 2011.

Sarah Dulson, PhD, Regulatory Scientist, has over 10 years of experience in scientific research and writing, complemented by a year in Regulatory Strategy and Biometrics at Rho. Her work in regulatory strategy includes authoring and assisting in the development of modules for regulatory submissions (IND, NDA, BLA, etc.), documents crucial for FDA meetings, clinical study protocols and reports, and regulatory guidance memos. Dr. Dulson has supported regulatory activities for drug and device products across a diverse range of indications from general anesthesia to vaccines to hair growth, and she functions as a valuable resource for clients navigating product development to bring their product to market.