ANDA Reformulations Should Not Result In Loss Of 180-Day Exclusivity - Andrx

Reformulation of a product under ANDA review should not result in the loss of 180-day exclusivity eligibility, Andrx argued in Oct. 5 comments to FDA's 180-day generic exclusivity proposed rule.

In its August rule, FDA proposed that if a new Paragraph IV certification is filed due to a formulation change, the applicant may lose first filer status. FDA's proposal is based on the concern that "in the rush to be the first ANDA...applicants will submit the results of the first completed BE study, whether or not the results meet the standards for approval," then later amend the application (¹ ).

"This proposal is a remedy to a problem that does not exist," Andrx asserted.

"With few, if any, exceptions, bioequivalence studies are performed by third party contract research organizations," Andrx said. "Unless the agency is asserting impliedly that applicants and CROs are individually and collectively conspiratorial and untrustworthy, no basis exists for the agency's proposed provision."

Denying exclusivity to these applicants "ironically... might have the effect of delaying the marketing of a generic," Andrx noted, "as the first applicant might choose not to reformulate its non-approvable product in order to avoid losing the ability to waive its exclusivity 'right' in favor of a successful applicant."

Andrx has benefited from an exclusivity award despite significant ANDA changes; the firm's Cardia XT generic diltiazem was approved in June with first-filer 180-day exclusivity despite submission of a reformulation supplement. Faulding subsidiary Purepac argued in a citizen's petition to FDA that Andrx should lose its exclusivity eligibility because of the reformulation (² (Also see "Purepac Challenges Andrx Cardia XT Exclusivity On Reformulation Grounds" - Pink Sheet, 16 Aug, 1999.)).

Applicants should lose exclusivity rights if formulation changes are motivated by court decisions holding a patent infringed or if FDA found the initial formulation not approvable, Andrx conceded, calling those reformulation efforts "salvage initiatives only."

Andrx suggested that the exclusivity "trigger period" proposed in the rule may be outside of FDA's authority. "FDA has chosen to create 'triggers' not identified in the [Waxman/Hatch] statute. For purposes of this comment, we assume at this time that the proposed provision is within the agency's rulemaking authority," Andrx said.

The proposed 180-day "trigger period" requires companies to market their approved generic within six months or lose exclusivity. The "trigger period" begins when a competitor receives a tentative ANDA approval for the same drug.

Andrx' own actions may have been one factor in FDA's trigger period decision: Andrx received $10 mil. per quarter payments from Cardizem CD NDA holder Hoechst to defer marketing of generic diltiazem until resolution of the companies' ongoing patent case. Abbott entered into similar arrangements with generics firms Ivax and Geneva to protect Hytrin.

Andrx also took issue with FDA's denial of a "rolling exclusivity" in favor of limiting exclusivity to the first Paragraph IV ANDA filer only.

The proposed regulations "are focused, almost exclusively, on elimination of exclusivity for ANDAs that do not beat the clock (the triggering event)...If the first applicant cannot be approved, or cannot or will not engage in commercial marketing, the proposed regs eliminate the mandated reward instead of providing a continuing incentive to reward a subsequent applicant that succeeds in being the first to make a generic product available," Andrx argued.

"If the first filer cannot or does not cause a generic product to be commercially marketed, exclusivity should be provided to the first such applicant that is prepared and is able to engage in commercial marketing without delay," Andrx emphasized, stating "limiting exclusivity to the first Paragraph IV applicant is an outcome not dictated by the statute."

FDA decided against rolling exclusivity to prevent "further delay [of] entry into the market of generic drug products with no countervailing public benefit."

Andrx responded, "were this FDA assessment theoretically correct...the agency cannot, as a matter of law, and should not, as a matter of policy, eliminate or unduly restrict the mandated reward simply because it desires to foster more rapid entry of generic products into the marketplace."