Medicis Challenges FDA’s Policy on Hatch-Waxman Benefits for Combination Drugs Containing an “Old” Antibiotic

April 27, 2007

On April 20, 2007, Arnold & Porter submitted a citizen petition and a petition for stay of action on behalf of Medicis Pharmaceutical Corp. asking FDA to change the Agency’s policy with respect to Hatch-Waxman patent and exclusivity benefits for combination drugs containing a so-called “old” antibiotic.  “Old” antibiotics are antibiotic active ingredients (and derivatives of such ingredients) included in an application submitted to FDA for review prior to November 21, 1997, the date of enactment of the 1997 FDA Modernization Act (“FDAMA”).  The Medicis petitions concern the company’s combination drug product ZIANA (clindamycin phosphate; tretinoin) Gel, which the Agency approved in November 2006 for the treatment of acne vulgaris, and which contains the “old” antibiotic clindamycin. FDA’s decision on the Medicis petitions will determine whether such combination drugs are eligible for Hatch-Waxman patent and non-patent marketing exclusivities.

The Medicis citizen petition asks that FDA:

1. . . . .reconsider, as a matter of policy, its current position that any combination drug that has, as one of its active ingredients, a pre-1997 antibiotic ingredient is denied the incentives of market exclusivity and patent listing in that FDA reverse that position[; and]

2. . . . list the patent submitted for the Medicis product Zianaä and acknowledge the 3-year period of market exclusivity earned by that product.

The Medicis petition for stay of action asks that FDA:

1.  prevent the approval of any ANDA or Section 505(b)(2) application referencing the Zianaä NDA during the 3-year [period] of market exclusivity that would be earned by the Zianaä application if the citizen petition is granted, and

2.  provisionally list the patent submitted by Medicis for Zianaä in the Orange Book.

FDA’s policy on patent and exclusivity benefits for combination drugs containing “old,” pre-FDAMA antibiotics stems from the Hatch-Waxman Act, which excluded antibiotic drugs approved under FDC Act § 507 from such benefits. 

FDAMA repealed FDC Act § 507 and required all NDAs for antibiotic drugs to be submitted under FDC Act § 505.  FDAMA included a transition provision declaring that an antibiotic application approved under § 507 before the enactment of FDAMA would be considered to be an application submitted, filed, and approved under FDC Act § 505. 

Congress created an exception to this transition provision.  FDAMA § 125(d)(2) exempts certain antibiotic applications for antibiotic drugs from those provisions of § 505 that provide patent listing, patent certification, and marketing exclusivity.  Specifically, FDAMA § 125(d)(2) exempts an antibiotic application from Hatch-Waxman benefits when “the drug that is the subject of the application contains an antibiotic drug and the antibiotic drug was the subject of an application” received by FDA under § 507 of the FDC Act before the enactment of FDAMA (i.e., November 21, 1997). 

Thus, applications for antibiotic drugs received by FDA prior to November 21, 1997, and applications submitted to FDA subsequent to November 21, 1997 for drugs that contain an antibiotic drug that was the subject of an application received by FDA prior to November 21, 1997 are within the FDAMA § 125(d)(2) exemption and are not eligible for Hatch-Waxman benefits.  Applications for antibiotic drugs not subject to the FDAMA § 125(d)(2) exemption are eligible for Hatch-Waxman benefits.  A 1998 FDA guidance document explains the effects of FDAMA § 125 in greater detail. 

On January 24, 2000, FDA published proposed regulations in the Federal Register that include a list of “old,” pre-FDAMA antibiotic drugs not subject to Hatch-Waxman benefits.  The list includes clindamycin.  FDA has not yet promulgated final regulations.  In addition to the specific chemical substances listed, the list also includes “‘any derivative’ of any such [listed] substance, such as a salt or ester of the [listed] substance.”

The Medicis petitions claim that FDA’s interpretation of FDAMA § 125(d)(2) “requires unwarranted verbal gymnastics with respect to the meaning of ‘drug,’” and that it:

is not a sensible way to read a statute.  Instead, Congress clearly intended the reference to “contains” to follow the normal understanding of the term: when one asks “what does a combination of tretinoin and clindamycin contain,” the answer is “tretinoin and clindamycin,” not “clindamycin” . . . .  Thus, the drug product is in common parlance the active ingredient or ingredients it contains.  If the word “contains” is read as intended to mean “is,” the statute then parses: the statutory incentives are not available when the drug product that is the subject of the application is an antibiotic drug product and that antibiotic drug product was the subject of an application for marketing under Section 507 on the FDAMA effective date.

If FDA grants the Medicis petitions, it is unclear how the Agency might retroactively apply its decision to approved marketing application for combination drugs containing an “old” antibiotic previously denied Hatch-Waxman benefits.

Categories: Hatch-Waxman