FDA Denies ECR & Laser GRASE Petitions Following Voluntary Dismissal of Related Lawsuits

By Kurt R. Karst –      

FDA recently denied (here and here) two citizen petitions (here and here) submitted on behalf of ECR Pharmaceuticals (“ECR”) and Laser Pharmaceuticals, LLC (“Laser”) requesting that FDA, among other things, reconsider its determinations that certain marketed unapproved drug products containing brompheniramine maleate (alone or in combination with pseudoephedrine HCl) and methscopolamine nitrate are not Generally Recognized as Safe and Effective (“GRASE”), and that FDA reconsider or stay taking enforcement action against companies marketing such drug products.  FDA’s petition decisions come on the heels of the voluntary dismissals of two separate but related Petitions for Review ECR and Laser filed earlier this year with the U.S. Court of Appeals for the District of Columbia Circuit. 

As we previously reported, ECR and Laser requested that the D.C. Circuit review and set aside FDA’s March 3, 2011 decisions that that their marketed unapproved drug products are not GRASE.  In a separate notice published in the Federal Register on the same day, FDA announced its intent to take enforcement action with respect to these and many other marketed unapproved cough, cold, and allergy drug products (see our previous post here).  The ECR and Laser lawsuits were voluntarily dismissed after FDA filed motions to dismiss the cases for lack of jurisdiction (here and here).

FDA’s petition responses, which are largely the same (but in the context of different drug products), first deny the petitions (interpreted by FDA to be petitions for stay and reconsideration) on procedural grounds.  “The Agency action you seek to stay – a Federal Register notice setting forth the Agency’s intent to take enforcement action – may not properly be the subject of a request for stay under the Agency’s regulations at 21 CFR 10.35,” FDA states in the Laser response (and echoed in the ECR response).  Moreover, FDA states that its regulation on reconsideration at 21 C.F.R. § 10.33 “does not authorize seeking reconsideration of other Agency actions, such as the ones that appear to be challenged in your Petition, namely FDA’s issuance of a Federal Register notice setting forth the Agency’s intent to take enforcement action against certain products determined to be unapproved new drugs and FDA’s determination in a Federal Register notice that certain products are not GRAS/E.”

Turning to the GRASE issues raised in both petition, FDA says that the products do not meet the applicable GRASE standards.  In doing so, FDA provides a nice refresher on what it means for a drug product to be GRASE, and therefore, not a “new drug” requiring approval of a marketing application. 

[U]nder section 201(p) of the FD&C Act, a drug is a new drug if its “composition” is such that the drug “is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof” (not GRAS/E).  Further under section 201(p), a drug that is so recognized is still a new drug if it has not “been used to a material extent or for a material time under such conditions.”

This definition includes two separate criteria, either of which is sufficient to make a product a new drug: (1) lack of general recognition of safety and effectiveness and (2) insufficient duration or extent of use.  In other words, evidence of use for a material time and to a material extent alone is insufficient to render a product not a new drug; it must also be GRAS/E.  Conversely, a GRAS/E drug that has not been used for a material time or to a material extent will be considered a new drug.

Citing decades of case law, FDA says that three criteria must be satisfied to support a GRASE claim:

First, the particular drug product must have been subjected to adequate and well-controlled clinical investigations establishing that the product is safe and effective.  Second, those investigations must have been published in the scientific literature so that they are available to qualified experts.  Third, experts must generally agree, based on those published studies, that the product is safe and effective for its intended uses.  A product’s general recognition as safe and effective must be evidenced by at least the same quality and quantity of data as are necessary to support approval of an NDA. [(Citations omitted)]

According to FDA, none of the products identified in the ECR and Laser petitions meet the criteria for GRASE status.  As such, the continued manufacture and shipment of the affected drug products past the deadlines FDA identified in its March 2011 notice “may result in legal action without further notice, including, without limitation, seizure and injunction.”