The Drug Enforcement Administration (DEA) issued a Notice of Proposed Rulemaking (NPRM) seeking to “revoke the exempted prescription product status for all butalbital products previously granted exemptions.”

If finalized as proposed, the significant impact of this change will be felt throughout the pharmaceutical supply chain.

The Controlled Substances Act and DEA’s regulations provide the agency with authority to exempt a prescription drug product containing a controlled substance from regulatory requirements and administrative, civil, and criminal sanctions.  DEA is authorized, among other reasons, to exempt nonnarcotic prescription drug products from application of all or any part of the CSA if the product also contains one or more active ingredients which are not controlled substances and in such quantities “as to vitiate the potential for abuse.“

The current list of Exempt Prescription Products (“EPP”) can be found here.

Butalbital prescription products, specifically those containing sufficient “quant[ities] of acetaminophen in the formulation, which was believed at the time to vitiate the potential for abuse[,]” have long been the poster child of the EPP (as opposed to the butalbital products containing caffeine and aspirin, which DEA has refused to exempt over the years). DEA states that there are 189 products on the EPP list that contain butalbital. This is slightly less than half of all the products on the list. DEA believes that all but 49 of the 189 butalbital products on the EPP have been discontinued. The NPRM also indicates that butalbital/acetaminophen products have enjoyed exempted status going back to 1967.

That is all about to change.

According to the NPRM, the agency

“has observed a pattern of diversion, online distribution, and abuse of exempted butalbital products. In particular, DEA has observed exploitation of the exempted prescription product status of butalbital combination products to enable abuse. Therefore, because the inclusion of acetaminophen has not vitiated the abuse potential of these products, DEA has concluded that these products do not meet the exemption criteria found in 21 U.S.C. 811(g)(3)(A).”

Specifically, DEA notes an increase in the illegal sale of these products over the Internet. In support of the NPRM, DEA also reminds us that at least 15 states treat all products containing butalbital as Schedule III controlled substances.

What does all of this mean for the pharmaceutical supply chain if the proposed rule is finalized? Here are a few areas for industry to noodle on when considering whether to comment on this rule:

  • By removing the exempted status, DEA will have the Ryan Haight Act as a tool to combat the sale of these products via the Internet. Practitioners, in most circumstances, will have to conduct at least one in-person medical examination before prescribing butalbital products and online pharmacies “will be required to cease the sale and distribution of the products containing butalbital,” unless they are in compliance with the Ryan Haight Act;
  • All butalbital products will need to be properly labeled with the CIII designation;
  • A DEA registration will be required for anyone who manufactures, distributes, dispenses, etc., products containing butalbital;
  • DEA registrants will be required to store butalbital products as they would other Schedule III products, maintain complete and accurate records and inventories (including an initial inventory when the rule takes effect) of all butalbital products, and prescriptions for butalbital products would be required to comply with the CSA and DEA’s regulations; and
  • Distributors will be required to include all butalbital products in their respective suspicious order monitoring programs.

As this is just a proposed rule, the public still has an opportunity to impact what is included in the final rule.  Comments must be submitted on or before May 12, 2022.