Last month I published an essay that analyzed the exemption language related to combination products contained in the old California pedigree law and in H.R. 3204, which was later signed into law as the Drug Quality and Security Act (DQSA) (see “Drug-Device Combo Products Under State And Federal Pedigree Laws”). In that essay I showed how these exemptions were very similar because both were based on the existing definition of a “combination product” from 21 CFR 3.2(e). My assessment of the effect of the wording in the old California pedigree law is still valid, in my opinion, but I now believe my analysis of the language in H.R. 3204 was incorrect. Here is why.
Of course, in the ensuing weeks the California law has been preempted by the enactment of the DQSA, the official designation for what was formerly referred to as H.R. 3204 (see “It’s Official, President Obama Signs H.R. 3204, DQSA, Into Law” and “Preemption: What Does It Mean?”). What a difference a month can make. We are now looking at a slightly familiar but definitely different regulatory landscape.
COMBINATION PRODUCT EXEMPTION LANGUAGE. WHAT CHANGED?
The combination product exemption language did not change from last month’s version of H.R. 3204 to the final language of the DQSA, but my interpretation of it has. In my previous essay I focused on the language that closely matched that contained in the old California law, but in the DQSA that isn’t the whole exemption clause. The full clause from Section 581(24)(B) of the DQSA is extracted here:
“(xii) a combination product that is not subject to approval under section 505 or licensure under section 351 of the Public Health Service Act, and that is—
(I) a product comprised of a device and 1 or more other regulated components (such as a drug/device, biologic/device, or drug/device/biologic) that are physically, chemically, or otherwise combined or mixed and produced as a single entity;
(II) 2 or more separate products packaged together in a single package or as a unit and comprised of a drug and device or device and biological product; or
(III) 2 or more finished medical devices plus one or more drug or biological products that are packaged together in what is referred to as a ‘medical convenience kit’ as described in clause (xiii);”
The part that closely matches the old California law are the sub-clauses (I) through (II). But, obviously, to fully understand the meaning behind the exemption you need to analyze the full clause. Before you even get to the meaning of the sub-clauses, you first have to have a product that fits the first part of the full clause. That is, a product that meets the following:
“…a combination product that is not subject to approval under section 505 or licensure under section 351 of the Public Health Service Act…”
Because of the “or” in this sentence fragment, the exemption applies to “a combination product that is not subject…” to one of two things:
- approval under section 505
- licensure under section 351 of the Public Health Service Act
A product that does not fit either of these two conditions might be exempt from the DQSA. To know for sure you have to continue analyzing the sub-clauses (I) through (III)—including the analysis that my earlier essay focused on exclusively.
BUT MOST OF YOU REALLY DON’T EVEN NEED TO LOOK AT THE SUB-CLAUSES
There are quite a few exemptions itemized in the Drug Supply Chain Security Act (DSCSA) that is Title II of the DQSA. Each exemption has a specific reason, I’m sure, but those reasons are not articulated in the law itself. All of them are carefully designed to exclude a small set of products from the rigorous implementation of the law. The vast majority of drugs and biologics will not fit into any of these exemption clauses. So, if you are trying to figure out if this combination product exemption definitely does NOT apply to a specific product, you may not even need to analyze those three sub-clauses, because most drugs and biologics will not even make it past these two first parts.
If a combination product is subject to “approval under section 505”, that means the FDA regulates it as a drug. That means the combination product’s “primary mode of action” or PMOA, is as a drug. If a combination product’s PMOA is not a drug, then it is regulated by the FDA as either a biologic or a device, in which case it is not subject to “approval under section 505”.
If a combination product is subject to “licensure under section 351 of the Public Health Service Act”, that means the FDA regulates it as a biologic. That means the combination product’s “primary mode of action” or PMOA, is as a biologic. If a combination product’s PMOA is not a biologic, then it is regulated by the FDA as either a drug or a device, in which case it is not subject to “licensure under section 351 of the Public Health Service Act”.
Putting these two together in the same form as the first part of the DQSA combination product clause, if a combination product is not subject to “approval under section 505” or “licensure under section 351 of the Public Health Service Act”, that means the FDA does not regulate it as a drug or a biologic. By default, that means the combination product is regulated by the FDA as a device. Its “primary mode of action” or PMOA, is a device, even though it may also contain a drug and/or a biologic component.
By this logic, it appears that this exemption only applies to combination products that are regulated by the FDA as devices, or at least only those that are not regulated as drugs or biologics. That makes sense to me because it greatly reduces the number of products in the market that fall into this exemption category compared to the similar exemption in the old California law.
So, to be clear, my current interpretation of this whole exemption is that most combination products that have a PMOA of a “device” do not have to follow the DQSA, and thus, all combination products that have a PMOA of a drug or biologic are not exempt from the DQSA (by this particular exemption anyway).
WHY DIDN’T THEY JUST SAY THAT IN THE FIRST PLACE?
I think the reason they did not say it that way is to make it clear that, even though device PMOA combination products can contain one or more drugs and/or biologics, they are still exempt. If they didn’t say it, people would wonder if those embedded drugs and/or biologics might need to comply with the DQSA. According to my interpretation of this exemption, they don’t.
What’s really interesting is how similar the exemptions seem between the old California pedigree law and the DQSA, but how different they turn out to be in implementation. The California law would have exempted pretty much all combination devices regardless of PMOA but it appears that the DQSA only exempts those with a PMOA of a device. In those products, the drug and/or biologic components play only a secondary role.
This is my interpretation. Make your own determination before you take action. If you aren’t sure if your combination product falls into this exemption, I suggest you have a conversation with the FDA Office of Combination Products.
Shortly after this current essay is published I will modify the old essay to direct readers who stumble upon it to this new essay so they are not potentially confused.
Do you agree with my new interpretation of this exemption or do you have a different interpretation? Leave a comment below.
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