|A combination product 's regulatory |
pathway can go through one of three
primary review jurisdictions.
by Winston Brown,
VP of Global Quality & Regulatory Affairs Phillips-Medisize
Determining Your Product’s Regulatory Pathway
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While a product could feasibly have more than one mode of action, which is how it achieves its intended therapeutic effect or action, the FDA wants the sponsor company to define the single-most important (or) primary mode of action. This key piece of information determines the product’s regulatory pathway, and allows the sponsor to begin the process of submitting its drug device combination product for approval. Should the wrong PMOA be identified, the application may be delayed by the Office of Combination Products (OCP). The delays could be in the form of not going to the correct review jurisdiction, eliciting questions back from the reviewing agency that will need to be answered by the sponsor, or a combination thereof.
Companies that know their products well or have a product that is comparable to a proven drug product already on the market may file a 503(b)(2), which allows them to take an abbreviated product regulatory pathway for drugs. However, in cases where a PMOA cannot be defined with certainty, the sponsor should seek assistance from an experienced retained consultant and the OCP.
When In Doubt, Turn To OCP
One of the primary responsibilities of the OCP is to assign the appropriate review jurisdiction to a sponsor’s combination product, through the sponsor company filing for a Request for Designation (RFD). It is important to note that the OCP establishes policy and guidance specific to combination products, but does not review the actual products for safety, effectiveness, efficacy, superiority claims, and like criteria. The latter is the job of the actual reviewing office whereby the product is actually assigned by OCP. In the FDA guidance document, How to Write a Request for Designation, the agency outlines all of the information necessary to file the RFD. This includes the PMOA for each constituent of the product as well as the PMOA for the overall combination product “system.” Other useful resources can be found on the OCP website, such as Capsular Descriptions of Jurisdictional Determinations, which provides pre-decisions for jurisdictional review for certain types of products.
Some of the factors OCP will consider when reviewing the RFD are:
- Why would the product be used?
- How does the product work?
- If any preliminary, pre-clinical exploratory studies have been done, what data is available?
- What is the intended use of the product, based on advertising and promotional materials?
- Are there any precedents currently on the market or pending final approval? (if it’s a first-in-kind product, there may not be)
- What safety and effectiveness issues are raised because of the uniqueness of the product?
A sponsor should anticipate these questions when going through the early-stage development process, in order to have a firm grasp on the answers prior to filing. Without doing so, the process of completing the RFD could be delayed or the company could face these questions later on from the OCP.
Once the RFD has been submitted, the OCP responds within five calendar days to indicate whether or not additional information is needed. If there are questions, a sponsor may receive an inquiry from the OCP. Inquiries or questions should be answered as quickly and completely as possible, so as not to delay the process. The OCP then has 60 calendar days to respond back to the sponsor company regarding next steps.
If the OCP is not able to make a determination of the product PMOA (or) cannot do it with certainty, the PMOA will then be determined based on the agency algorithm. If the algorithm is applied, the OCP first attempts to determine which of its offices has the most experience with similar products that present the same questions of safety and efficacy. If so, the sponsor’s combination product is assigned to the same office as that product. If OCP is unable to identify a similar product, then the sponsor’s product is assigned to the office with the most expertise related to the most significant safety and effectiveness questions presented by the combination product. There are several other factors relevant to the application of the algorithm outlined in the guidance document.
After The Request for Designation
One hypothetical example would be for the manufacturer of a novel device that delivers an already known drug product. The route of delivery to the sponsor company (the device) might be the single most important mode for therapeutic effect. However, without a sufficient case being provided by the sponsor, the agency may categorize the product as a drug. Thus, the proposed reviewing office, the CDER in this case, may require extensive clinical data studies based on unfamiliarity with the device portion of the product. Conversely, were the product to have been assigned to CDRH, the required clinical studies would in theory be more specific to the device in proving out an already existing drug. The information provided in the response cannot merely repeat the information that was provided in the RFD. Any new information should be summarized in the response and provided as an addendum to the original request. An RFD application also may not exceed 15 pages in submission.
- Transparency Market Research: Drug Device Combination Products Market (Drug Eluting Stents, Infusion Pumps, photosensitizers, Orthopedic Combination Products, Wound Care Combination Products, Inhalers, Transdermal Patches, Intraocular Implants and Drug Eluting Beads) - Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2013 – 2019. December 24, 2013.
- U.S Food and Drug Administration, Code of Federal Regulations (CFR). 21 CFR Chapter 1: Part 3, Sub-section 3.2 (e).
- FDA Performance Report To Congress: FY 2014: Office of Combination Products.
Reprinted with author's permission.
Winston R. Brown works for Phillips-Medisize Corporation, as their Vice President of Global Quality & Regulatory Affairs. Winston has worked in the pharmaceutical, medical device and bio therapeutics industries for 20+ years. Subsequent to serving in the United States Army, he has held positions of increasing responsibility in quality, regulatory, and operations at Johnson & Johnson Consumer Pharmaceuticals, Holopack, USA, Bausch & Lomb, Baxter Healthcare and Alcon, a division of Novartis. Winston earned undergraduate degrees in Microbiology, Operations Management, and Medical Technology. His graduate degrees include an MBA and MS Degree in Pharmaceutical Engineering, and has completed post graduate work at the University of Southern California.