In an attempt to delay private-label competition for Mucinex OTC cough products, Reckitt Benckiser asks FDA to ensure potential generics meet the same bioequivalence across the 12-hour dosing interval as the branded product.

Reckitt Benckiser argues in a July 14 citizen ¹ petition that "FDA should carefully examine" the pharmacokinetic profile of any generic product that references Mucinex (guaifenesin) in an abbreviated new drug application because the agency "carefully reviewed the PK profile" of Mucinex prior to the product's approval.

Specifically, Reckitt says FDA should ensure generic products have the same time to maximum plasma concentration (Tmax) and maximum plasma concentration (Cmax) as Mucinex, and are therapeutically effective for 12 hours -- or have the same area under the plasma concentration time curve (AUC) -- as Mucinex.

FDA should consider generic Mucinex products that fall short of these standards "misbranded" and inappropriate to market, Reckitt adds in the petition.

If accepted, the petition could substantially delay generic competition if private-labelers take as long to develop their modified-release guaifenesin products as development took Adams Respiratory Therapeutics, the Mucinex originator acquired by Reckitt in 2008 (² Also see "Reckitt Benckiser Looks Overseas To Double Adams’ Revenue" - Pink Sheet, 17 December, 2007.).

Mucinex Originator Set The Standard

According to the petition, it took four years of "considerable development work" to create Mucinex MR and to assure FDA the modified release formulation's Tmax was as fast as and the Cmax was equal to immediate release Mucinex's, and its AUC supported a 12-hour dose.

Adams reached these requirements by creating a tablet with immediate- and sustained-release layers that "provided an early Cmax boost (like an IR product) necessary for efficacy soon after dosing and also provided a sustained release form of guaifenesin."

To bolster its argument, Reckitt points to a precedent FDA set in May 2009 when it told prescription drug Doryx manufacturer Warner Chilcott that "ANDA applicants must demonstrate bioequivalence under the dosing conditions described in the labeling" of the branded product.

Like Reckitt, Warner Chilcott asked FDA to require ANDA applicants that reference Doryx to conduct bioequivalence studies under all dosing conditions in the label.

FDA agreed and added in the Doryx ³ decision that the agency "carefully reviews Tmax during its review of generic products," according to Reckitt's petition.

"The need to review Tmax was based presumably on FDA's desire to ensure that the generic product have a comparable PK profile to that of the reference listed drug," Reckitt explained.

Extending OTC Exclusivity

The petition is the latest attempt to delay rapidly approaching generic competition for Mucinex.

The U.K.-based firm's patents for Mucinex expire in April 2020, but United Research Labs/Mutual Pharmaceuticals, Perrigo and Watson Pharmaceuticals already filed ANDAs for the generic single-ingredient Mucinex. Watson also filed an ANDA to market a private-label version of Mucinex DM (guaifenesin and dextromethorphan) and Mucinex D (guaifenesin and pseudoephedrine) (⁴ Also see "Watson Files ANDA For Mucinex DM, Gets In Line For Generic Guaifenesin" - Pink Sheet, 27 April, 2009.).

Adams sued the ANDA sponsors, alleging the firms committed patent infringement by certifying to FDA in their applications that the Mucinex patents are invalid and unenforceable.

Under a settlement with Adams, URL/Mutual could sell generic Mucinex as early as July 2012, if approved by FDA (⁵ Also see "Adams Reinforces Mucinex Patents In Settlement Agreement With Mutual" - Pink Sheet, 26 March, 2007.).

Patent litigation with Perrigo is pending still, but "the next key milestone event in the suit is the judge determining claim construction," a Perrigo spokesman said.

Patent litigation with Watson also is pending, according to court documents in the U.S. District Court for the Southern District of New York.

-- Elizabeth Crawford (e.crawford@elsevier.com)

Reckitt Bids To Delay Mucinex Competition With Bioequivalance Petition

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