Reckitt Benckiser's petition seeking to define specific bioequivalence standards for private-label versions of Mucinex OTC cough products, if followed, would push FDA to violate generic drug law, Perrigo argues.

In a Dec. 7 ¹ letter to FDA, the private labeler says Reckitt makes an "anticompetitive" and "baseless" argument to subject abbreviated new drug applications for extended-release guaifenesin products requirements that go beyond the Hatch-Waxman definition of bioequivalence.

Allegan, Mich.-based Perrigo, which filed an ANDA for extended-release guaifenesin products, says the request in Reckitt's July 14 citizen ² petition "is nonsense and cannot lawfully be granted."

Perrigo notes that by law, generic applicants are subject to different approval requirements than sponsors of new drug applications, who need only show a generic product is bioequivalent "to the reference listed drug and has the same active ingredient, dosage form, dosage strength, route of administration and labeling" as the branded drug.

Reckitt's petition framed its argument as defining bioequivalence in the case of Mucinex, not as seeking requirements beyond bioequivalence.

Reckitt asks FDA to "carefully examine" the pharmacokinetic profile of any generic product that references Mucinex (guaifenesin) in an ANDA to ensure the product has the same time as Mucinex to maximum plasma concentration (Tmax) and the same duration of maximum concentration (Cmax).

The petition also asks the agency to ensure ANDAs for generics of the branded drug have effective plasma concentrations - or therapeutic effectiveness - to justify a 12-hour dosing interval (³ Also see "Reckitt Bids To Delay Mucinex Competition With Bioequivalance Petition" - Pink Sheet, 27 July, 2009.).

One apparent implication of Reckitt's request is that generic drug makers for this product might have to study the product in sick patients to show, for example, efficacy at 12 hours, which is extraordinarily expensive, time-consuming and "essentially eviscerates the whole Waxman-Hatch ANDA scheme," said Irving Wiesen, a lawyer in the Law Offices of Irving L. Wiesen in New York.

Wiesen is not employed by Perrigo but worked for the firm several years ago on an unrelated matter.

"The whole point of Waxman-Hatch was to allow generic drugs on the market, which for most products means simply showing" a generic product has a similar rate and extent of active ingredient plasma concentrations to the branded product, he said. "Ipso facto, the product will have the same therapeutic profile."

"FDA, Congress, the courts and the whole world" know this is how to get an ANDA for most products, he said.

Reckitt Points To FDA Precedent

However, Reckitt argues generic drugs should meet the same requirement its branded drug needed to meet - mainly that the extended-release formula's Tmax was as fast as and the Cmax was equal to immediate-release Mucinex.

For support, Reckitt points to a precedent FDA set in May 2009 when it agreed with prescription drug Doryx manufacturer Warner Chilcott that ANDA applicants must demonstrate bioequivalence under the dosing conditions in the branded drug's labeling, and said it would review closely the applicants' Tmax.

If FDA agrees, generic competition likely will be significantly delayed, given that it took Mucinex originator Adams Respiratory Therapeutics four years to demonstrate the standards. Reckitt acquired Adams in 2008.

Perrigo argues, however, that the Doryx case does not support Reckitt's request because it "did not create a new statutory or regulatory Tmax requirement."

Rather, Perrigo says, the Doryx decision relied, in part, on the food-effect guidance, "which explicitly states that when assessing bioequivalence, 'no criterion applies to Tmax.'"

Perrigo also argues FDA should deny the petition because "Reckitt offers no scientifically valid reason to believe that FDA's current criteria are insufficient to demonstrate the bioequivalence of generic guaifenesin products or to deviate from FDA's existing bioequivalence requirements."

Nor does Reckitt explain how the additional bioequivalence standards, such as an "early Cmax," relate to safety or efficacy concerns, Perrigo says.

Perrigo Says Petition Is Merely A Delay Tactic

In light of these missing data, Perrigo says the sole purpose of Reckitt's petition is to delay market entry of competing generic products.

Perrigo calls the petition "the latest in a long string of anticompetitive brand petitions aimed at delaying the introduction of lower-priced generic products."

Wiesen agrees the petition is likely a delay tactic and believes it has little real merit.

"It appears that Reckitt is hoping here that the FDA will, on the basis of this petition, put a halt to the [ANDA] approval proceedings until it can address the petition," he explains, adding, "but what the FDA does, no one can predict."

Perrigo invokes in its letter provisions of the FDA Amendments Act of 2007 that, it says, "expressly reiterated that the agency cannot lawfully delay ANDA approvals because of a pending citizen petition" unless FDA determines, upon reviewing the petition, a delay is necessary to protect public health.

Perrigo adds, "Reckitt's three-page petition raises no valid safety or efficacy concerns."

Perrigo also argues the petition is an attempt to "assist Reckitt in patent litigation it has brought against ANDA filers," including Perrigo.

Other private label firms currently or previously embroiled in patent litigation related to guaifenesin products are Watson and United Research Labs/Mutual (⁴ Also see "Watson Files ANDA For Mucinex DM, Gets In Line For Generic Guaifenesin" - Pink Sheet, 27 April, 2009.).

URL/Mutual resolved the litigation with Adams in 2007 and under the settlement could sell generic Mucinex as early as July 2012 even though the patents expire in 2020.

In the context of these hurdles Reckitt tried to erect in front of generic competition, Perrigo urges FDA to deny the petition, noting, "Reckitt has enjoyed a monopoly over the extended-release guaifenesin market long enough."

- Elizabeth Crawford ( ⁵ e.crawford@elsevier.com )

Perrigo Claims Reckitt's Bid To Block Generic Mucinex Is "Baseless"

More from Archive

More from Pink Sheet