Both the California ePedigree law and the potential federal pedigree law that currently exists within the womb that is H.R. 3204 contain an exemption for drug-device combination products. This is an expanding category of products so this exemption is worthy of a closer look.
The drug-device combo product exemption language included in the California Business and Professions Code, 4034(g)(9), is almost identical to the language in H.R. 3204, 581(24)(B)(xii). There is a reason for that. They are both based on part of the FDA’s definition for a drug-device combination product, found in 21 CFR 3.2 (e).
Here is the text from the drug-device combo product exemption from the California law, 4034(g)(9):
“(A) A product comprised of two or more 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.
“(B) Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products or device and biological products.”
Here is the text from the drug-device combo product exemption from H.R. 3204, 581(24)(B)(xii):
‘‘(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;…”
Finally, here is the source text from 21 CFR 3.2 (e) that represents part of the definition of a “combination product”:
“(1) A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity;
“(2) Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;”
START WITH THE PRIMARY MODE OF ACTION
Since at least 2005 the FDA has regulated combination products in a special way. Drug-device combinations are evaluated to determine the “primary mode of action” (PMOA). The PMOA can be either the device or the drug. An example of a device PMOA combination product is a drug-eluting stent. In that case, the primary therapeutic value comes from the physical device—the stent—and the drug only provides an enhancement, or a secondary therapeutic value. An example of a drug PMOA combination product is a metered dose inhaler. In that case, the primary therapeutic value comes from the drug and the device merely provides an easy-to-use way to allow the patient to self-administer the proper dosage of the drug every time.
In a few cases it is not obvious whether a combination product’s PMOA is the drug or the device—even to the applicant or to the FDA. In those cases the FDA just flips a coin to decide which way to designate the product (just kidding, I’m sure there is some laborious and time-consuming process to make the determination).
The important thing for our purposes is that drug-device combination products are only required to be identified by either a National Drug Code (NDC) when the PMOA is the drug, or a Unique Device Identifier (UDI) when the PMOA is the device, not both. That eliminates device PMOA combo devices from these pedigree regulations right away because they would not have an NDC. They are regulated as “devices”, not “drugs”.
But the drug-device combination product exemptions built into the California law and H.R. 3204 ensure that even most drug PMOA products are exempt. You don’t have to guess whether or not your product fits into one of the categories listed in the exemptions—and the California Board of Pharmacy is not going to tell you because it is not up to them. The FDA should have classified your product as a combination product as part of your product registration. If your product was registered prior to 2005 and you don’t have a subsequent classification, contact the FDA Office of Combination Products (OCP).
However, be aware that there are two additional clauses (3 and 4, not included above) that open up the definition of combination products in the 21 CFR 3.2 text but which are not included in either of the two pedigree law/bill texts. Some thinking may be required to determine if those extra clauses are the only reason your product is classified as a combo product. When your product is close to the line, I recommend that you contact the FDA.
One way to help figure out if your product fits in to the first two clauses is to compare it to some product types that are known to be covered by them. Examples listed on the FDA website of the type of products that meet the first clause of the combination product text include:
- Monoclonal antibody combined with a therapeutic drug,
- Prefilled syringes,
- insulin injector pens,
- metered dose inhalers,
- transdermal patches
Examples listed that meet the second clause include:
- Drug or biological product packaged with a delivery device
- Surgical tray with surgical instruments, drapes, and lidocaine or alcohol swabs
More general examples of actual types of combination products, although without the all-important identification of which clause triggered their classification, can be found here.
SO YOU ARE EXEMPT. ARE YOU DONE HERE?
Apparently the California legislature and Congress (or at least the authors of these law/bill) believe that counterfeiters are less likely to counterfeit the drug plus the device necessary to administer it and so their exclusion reflects somewhat of a risk-based approach. Manufacturers of these products may be happy about that, or they may choose to voluntarily protect their products with serialization and pedigrees to elevate the barriers to illegitimate activity surrounding their combo products. That not only offers protection against counterfeiting, but enables additional protections against theft, diversion, reimbursement fraud and improper chargeback claims, among other potential benefits.
If you are thinking about following this path make sure you check with your wholesaler(s) to make sure they will commit to handling your product as if it were under a serialization and pedigree requirement. If your product is exempt from one of these laws they may not be interested in going through the extra business processes necessary for the distribution of serialized and pedigreed products. In that case, some of your projected benefits may not be attainable. Don’t assume they will handle your exempt products in any way beyond their legal obligation. If combo products are exempt for you, the manufacturer, they are exempt for the wholesalers too. I am sure you can work it out, but it may not happen without some prior agreement.
And remember, nothing is free in this supply chain.