Drug or Device? – FDA provides more clarity – or does it?
Industry has complained for years, and for good reasons, that it is difficult to understand FDA’s determination of whether a combination product would be reviewed as a device or a drug. So, in response to the signing into law of Section 3038 of the 21st Centuries Cures Act (primarily found at 21 USC 353(g)), FDA recently issued a final guidance “Classification of Products as Drugs and Devices & Additional Product Classification Issues: Guidance for Industry and FDA Staff.” Section 3038 codified changes in the way FDA is to handle combination products, specifically addressing the definition of “Primary Mode of Action.” (PMOA) Among other items, the statute specified that FDA cannot determine that a combination products PMOA is a drug or biologic solely because the combination product has any chemical action within or on the body. (emphasis added)
The new guidance consists of five primary sections:
II. What is the Process for Obtaining a Formal Classification Determination for a Product?
III. What does FDA Consider In Determining Whether To Classify A Product As A Drug Or Device?
IV. Additional Information, followed by a brief FAQ list
V. Illustrative examples
The first two sections are pretty much as described. Section II lays out the mechanics of obtaining a classification for a product, including how to handle a request for reconsideration should the Sponsor desire one, as well as FDA’s option to reclassify should, e.g., the indication for the product change. Worth noting is the statement that FDA intends to respond in writing to requests for classification in sixty days, but if it does not, citing 21 USC 360bbb-2(b) and (c) “…the sponsor’s recommendation respecting the classification of the product is considered to be the final determination.”
Section III contains the core of the guidance. The focus of the whole guidance, by FDA’s own admission, is whether a product is a drug or a device; there’s the title of the guidance, the title of the Section and, for emphasis, footnote 6: “This section generally focuses on approaches for determining whether a product should be classified as a drug or a device, based on application of the statutory definitions for these terms under sections 201(g) and 201(h) of the FD&C Act (21 USC 321(g) and (h)), respectively.”
The Agency’s starting point for classifying a product as a drug or device is, unsurprisingly, the statutory definition of drug and device:
“FDA’s determination of whether to classify a product as a drug or device is based on statutory definitions, as set forth in sections 201(g) and 201(h) of the FD&C Act, respectively. We apply these definitions to products, relying on the scientific data that are available to FDA at the time of the classification determination concerning the product for its proposed use(s)/indication(s).”
Section 201(g) of the FD&C Act (21 USC 321(g)) provides that the term “drug” means: (A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any articles specified in clause (A), (B), or (C). . . .
Section 201(h) of the FD&C Act (21 USC 321(h)) provides that the term “device” means: an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is–
(1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
(3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. (emphasis added)
Next, Section III(B) opens with a statement which begins to get at the central problem both FDA and industry confront for classification issues:
“Conceptually, all FDA-regulated medical products meet the definition of “drug” under section 201(g) of the FD&C Act, due to the broader scope of the drug definition. For a medical product also to meet the more restrictive device definition under section 201(h) of the FD&C Act, it must (i) be “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article,” and (ii) “not achieve its primary intended purposes through chemical action within or on the body of man or other animals” and (iii) “not [be] dependent upon being metabolized for the achievement of its primary intended purposes.” (emphasis added).
So, one way of looking at it might be that a product which is either a drug or device conceptually starts out as a drug, sort of by default, unless and until it’s demonstrated that the product meets the specific classification requirements of a device. And that’s fairly consistent with the apparent thrust of the changes instituted by the 21st Centuries Cures Act described above, i.e., changes designed to dial back the (at least perceived) tendency to lean towards defining products as drugs. FDA goes on to say that “…the focus of FDA’s classification analysis is on how the product would be expected to achieve its primary intended purposes, assuming it is capable of achieving its primary intended purposes at all.”
The guidance then narrows its focus to what FDA considers four key phrases in the definition of a device for determining a product’s classification:
- “Similar or related article” in the definition of device
- “Primary intended purposes” in the definition of device
- “Chemical action” in the definition of device
- “Within or on the body” in the definition of device
Similar or Related Article
This phrase comes at the end of the initial definition of a device, “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article . . .” In this section FDA seeks to clarify that products that may at first glance fall into the “drug” category, may qualify as a “similar or related article,” and thus be classified as a device. Not much specific rationale is provided. Instead, several examples are provided: gels or powders might act as barriers on the skin, gases might be used as space fillers and liquids might be used to clean surgical instruments or contact lenses. A useful clarification, but not groundbreaking.
Primary Intended Purposes
This phrase is part of the “exclusionary clause” providing that a device “…does not achieve its primary intended purposes through chemical action within or on the body of man or other animals . . ..” Here the FDA makes the distinction that while a product might have a chemical action, its primary intended purposes were not achieved through that action. Here again FDA illustrates with examples: When a hip joint replacement, designed to provide support and movement also elicits a foreign body response through chemical action, the chemical action is not the intended purpose, thus the exclusion does not apply. An absorbable suture is proffered as a second example.
FDA begins the section by pointing out that it frequently receives questions on this topic, and that the term “…must be read in the context of the statutory definition of “device” as a whole.” FDA reiterates the previously stated concept that a device may exert a chemical action so long the chemical action is not what achieves the primary intended purposes of the product. More specifically, the Agency states that in the context of interpretation of the device definition, “…a product exhibits “chemical action” if it interacts at the molecular level with bodily components (e.g., cells or tissues) to mediate (including promoting or inhibiting) a bodily response, or with foreign entities (e.g., organisms or chemicals) so as to alter that entity’s interaction with the body.” FDA further states that this definition is consistent with the term “pharmacological action” as understood in the “medical field”. The term is used throughout the remainder of the guidance.
Within or On the Body
Here FDA notes that a device can achieve its intended purposes via chemical action so long as the chemical reaction does not occur within or on the body. FDA considers this a “generally straightforward matter”. Two examples of devices which exert a chemical action to achieve intended purposes via chemical action but take place outside/not on the surface of the body are offered: a hemodialysis machine and transport solution, used to preserve a donated organ transportation.
In Section V FDA walks through a series of examples of products which do and do not exert their primary intended purposes through chemical actions within or on the body. The example descriptions are provided in fair detail, and provide a useful template of sorts illustrating FDA’s analysis of determining a drug v. device classification. The examples of products which “do not” achieve intended purposes via chemical action are the more useful here.
A brief discussion of how biologics fit into this scheme is also provided, followed by a very straightforward FAQ section.
Overall the guidance does not appear to signal a significant departure from FDA’s approach to classification, but offers some additional clarity for those considering development of a product whose classification might be an important consideration.
Premier Consulting has extensive experience in combination products, and can help navigate the classification, product development and product application process for clients in that arena. To learn more, contact us.
William Stoltman, J.D.
Senior Director, Quality Assurance and Regulatory Compliance