On November 1, 2010, the Deputy Administrator of the Drug Enforcement Administration published for the second time in three years a proposed rule to modify the listing of approved drug products containing dronabinol as Schedule III controlled substances under the Controlled Substances Act (“CSA”). See 75 Fed. Reg. 67054 (Nov. 1, 2010) (Listing of Approved Drug Products Containing Dronabinol as Schedule III). Dronabinol is commonly known as delta-9-tetrahydrocannabinol (“THC”), and is a federally-controlled Schedule I substance --- in all but one if its formulations. Marinol®, which is an FDA-approved synthetic formulation of THC in sesame oil encapsulated in a soft gel capsule, is regulated as a Schedule III controlled substance. See 21 U.S.C. § 1308.13(g)(1) (specifically, “Dronabinol (synthetic) in sesame oil and encapsulated in a soft gelatin capsule in a U.S. Food and Drug Administration approved product”). All other forms of THC, either natural or synthetic, and in whatever formulation (i.e., hard tablets, capsules, or other gel suspensions), are regulated as Schedule I controlled substances. Marinol® is the only drug product containing any form of THC that has been approved by the FDA.
The issue of universally reclassifying dronabinol in Schedule III is not a new one. The DEA first attempted to modify the listing of dronabinol back in 2007 (see blog entry dated October 1, 2007) (see 72 Fed. Reg. 54266 (Sept. 24, 2007) (Technical Amendments to Listing in Schedule III of Approved Drug Products Containing Tetrahydrocannabinois – Notice of Proposed Rulemaking.)
In 2007, the DEA proposed expanding the dronabinol Schedule III classification to include forms of the product other than the Marinol® formulation. The purpose of the 2007 proposed rule was to ensure that the generic versions of Marinol® would be classified in the same schedule as Marinol®, and not as a Schedule I controlled substance. The FDA and DEA expressed concern that the Marinol® formulation listed in Schedule III was (and still is) the only DEA listing in the CSA that has the (unintended) effect of excluding all generic versions of the brand name formulation. The DEA stated that listings of drugs based on differences in formulation is inconsistent with the structure and purpose of the CSA, which schedules drugs regardless of their formulation, and would result in a generic version being scheduled separately from the innovator drug. See generally 72 Fed. Reg. 54228-29.
Based on industry comments, the 2007 proposed rescheduling rule hit a road block in 2008. The DEA opted instead to require the application of the formal eight-factor statutory analysis set forth in 21 U.S.C. §811(c) for each generic version of dronabinol approved by FDA, and for transferring each approved dronabinol product from Schedule I to Schedule III based on that eight factor analysis. DEA also withdrew the 2007 proposed rule out of a concern that administrative appeals of any final rule could take years to resolve -- with no final regulation ever taking effect until well after the approval of generic forms of Marinol®. DEA believed the simpler form of action would be to continue to require the formal statutory rescheduling process for each individually FDA-approved generic form of the branded substance. See 73 Fed. Reg. 56533 (Sept. 29, 2008) (Technical Amendment to Listing in Schedule III of Approved Drug Products Containing Tetrahydrocannabinois; Withdrawal of Proposed Rule).
Now faced with four petitions from companies whose products are currently the subject of ANDAs under FDA review for a generic equivalent of Marinol®, the DEA is actively revisiting the issue of whether to amend the CSA regulations to expand the Schedule III classification of dronabinol to include generic versions of Marinol®. The 2010 proposed regulations seek to expand 21 C.F.R. § 1308.13(g)(1) to include: (1) both naturally-derived or synthetically-produced dronabinol; and, (2) hard or soft gelatin capsules. Contrary to the first attempt to reschedule dronabinol, this time the Assistant Secretary of Health, Department of Health and Human Services (“DHHS”), has chimed in by providing to the DEA Administrator supporting documentation, dated March 17 and June 1, 2010, recommending that FDA-approved, naturally derived, and hard- and soft-gelatin encapsulated dronabinol be placed in an expanded Schedule III definition of dronabinol.
The DHHS’s supporting documents contain a detailed review of the eight statutory factors set forth in 21 U.S.C. § 811(c). The DHHS’s recommendation of March 17, 2010 concluded that “drug products containing synthetic dronabinol in sesame oil and encapsulated in a hard gelatin capsule, have a similar potential for abuse as Marinol.” 75 Fed. Reg. 67057. (Emphasis added.) The FDA and the National Institute for Drug Abuse (“NIDA”) also reviewed available information and concluded that the hard capsule formulation of synthetic dronabinol should be a Schedule III controlled substance. Similarly, the DHHS’s scheduling recommendation of June 1, 2010 considered data and concluded that the naturally-derived form of dronabinol should be included in Schedule III. The DHHS’s scheduling recommendations for dronabinol are available for review on the DEA’s website. The DEA noted, as it did in 2007, that Congress structured the CSA so that there would be no distinction, for purposes of scheduling controlled substances, between the brand name and their generic counterparts. Thus, the 2010 proposed rule is yet another attempt to ensure that this principle holds true for generic versions of Marinol®.
In addition to the above analysis (and adopting a “belts and suspenders” approach not present in the 2007 proposed rulemaking) this time around the DEA also includes in the proposed rule a specific finding by the DEA Administrator that, “FDA-approved generic dronabinol products, both naturally-derived or synthetically produced, in sesame oil encapsulated in both hard gelatin or soft gelatin capsules meet the criteria for placement in schedule III set in 21 U.S.C. § 812(b).” The proposed rule next specifically details, factor by factor, why generic dronabinol formulations meet the eight-factor statutory test in 21 U.S.C. §811. The intended effect of the final rule will obviate the need for DEA to make a case-by-case determination, pursuant to 21 U.S.C. §812(b), whether a specific FDA-approved generic formulation of a dronabinol product will be listed as a Schedule III drug product. Those that meet the amended definition of 21 C.F.R. § 1308(g)(ii) will automatically be listed in Schedule III.
All comments on the proposed rule must be received by DEA on or before January 3, 2011.