Pending DESI Program Proceedings – The ListDecember 11, 2011
By Kurt R. Karst –
For years we’ve heard rumors of a relatively current list, compiled by FDA, of proceedings pending under the Drug Efficacy Study Implementation (“DESI”) program. At one time, in the early 1980s, the list was included as an addendum to the Orange Book, but was eventually removed from the publication. Since then, like the lost Ark of the Covenant, it has fallen into myth. But like the unwavering Indiana Jones, we initiated our own, FDA-type, archeological hunt, and were able to obtain a copy of FDA’s List of Pending DESI Proceedings. Fortunately, we didn’t have to deal with a large rolling boulder, dodge poison arrows, and wade through a sea of deadly asps, or battle with a guy named René Emile Belloq to get our prize. We just had to deal with the FOIA bureaucracy.
So what is the List of Pending DESI Proceedings and why is it of interest to some folks?
The DESI program, initiated in the wake of the 1962 Drug Efficacy Amendments, which amended the FDC Act to require that a new drug be proven effective, as well as safe, to obtain FDA approval, required FDA to conduct a retrospective evaluation of the effectiveness of the drug products the Agency had approved as safe between 1938 and 1962. That retrospective evaluation covered over 3,400 products that were approved only for safety between 1938 and 1962, as well as thousands more so-called “IRS” (identical, related, or similar, see 21 C.F.R. § 310.6(b)(1)) products that entered the market without FDA approval, for a total of 581 DESI reviews covering about 18,400 drugs.
Although FDA has completed most of the DESI proceedings initiated, a small number have remained unresolved for decades. These are the DESI proceedings termed “pending” and that are included in the list. The version of the list we obtained is as of August 2006 and lists seventeen items. Some of the DESI proceeding in the list have since been closed or are moving forward, such as various DESI cough/cold proceedings (see here) and the proceeding for Trimethobenzamide HCl Suppositories (see here).
Over the years, some companies have used the pending status of a DESI proceeding as a basis to market a particular drug product without obtaining approval of a marketing application from FDA. Indeed, although FDA states in the Agency’s most recent, September 19, 2011, iteration of its “Compliance Policy Guide: Sec. 440.100 Marketed New Drugs Without Approved NDAs or ANDAs,” (“Unapproved Drugs CPG”) that “any product that is being marketed illegally is subject to FDA enforcement action at any time,” the Agency also says that there is a general exception to this policy for marketed unapproved drugs subject to an ongoing DESI proceeding. FDA explains this exception in the Unapproved Drugs CPG as follows:
Some unapproved marketed products are undergoing DESI reviews in which a final determination regarding efficacy has not yet been made. In addition to the products specifically reviewed by the NAS/NRC (i.e., those products approved for safety only between 1938 and 1962), this group includes unapproved products [IRS] to those products specifically reviewed (see 21 CFR 310.6). In virtually all these proceedings, FDA has made an initial determination that the products lack substantial evidence of effectiveness, and the manufacturers have requested a hearing on that finding. It is the Agency’s longstanding policy that products subject to an ongoing DESI proceeding may remain on the market during the pendency of the proceeding. [Unapproved Drugs CPG at 10 (emphasis added).]
FDA also notes, however, that the pending DESI proceeding exception (like the so-called “grandfather” drug exceptions) is narrowly construed by the Agency:
Products first marketed after a hearing notice is issued with a different formulation than those covered by the notice are not considered subject to the DESI proceeding. Rather, they need approval prior to marketing. Under longstanding Agency policies, a firm holding an NDA on a product for which a DESI hearing is pending must submit a supplement prior to reformulating that product. The changed formulation may not be marketed as a related product under the pending DESI proceeding; it is a new drug, and it must be approved for safety and efficacy before it can be legally marketed. . . . Similarly, firms without NDAs cannot market new formulations of a drug without first getting approval of an NDA. [Unapproved Drugs CPG at 10, Footnote 15 (emphasis added).]
So, the List of Pending DESI Proceedings must be used with caution – caveat venditor! And keep in mind what happened at the opening of the Ark of the Covenant.