By Kurt R. Karst –
In a Complaint recently filed in the U.S. District Court for the District of New Jersey, Actelion Pharmaceuticals Ltd. and Actelion Clinical Research, Inc. (collectively “Actelion”) seek declaratory relief that Actelion is under no duty or obligation to supply prospective ANDA applicants, Apotex Corp. (“Apotex”) and Roxane Laboratories, Inc. (“Roxane”), with TRACLEER (bosentan) Tablets for purposes of bioequivalence testing and ANDA submission. TRACLEER is approved with a Risk Evaluation and Mitigation Strategies (“REMS”) program with Elements To Assure Safe Use (“ETASU”) because of the potential of the drug to cause serious side effects (see here). The REMS limits distribution of the drug through pharmacies, practitioners, and health care settings that are specially certified and that are “bound by contract to follow a strict protocol to monitor and protect patient health,” acording to Actelion. A prior case, brought by a prospective ANDA sponsor, that raised issues with providing a restricted distribution brand-name drug to an ANDA sponsor for biostudy purposes was eventually dismissed (see here). The Actelion case is the first preemptive strike by a brand-name company whose drug product is covered by an ETASU REMS. An on-the-merits decision would be the first of its kind since the REMS provisions were added to the FDC Act by the 2007 FDA Amendments Act (“FDAAA”).
According to Actelion, the lawsuit “concerns the fundamental right of a business to choose for itself with whom to deal and to whom to supply its products.” Apotex and Roxane both sent correspondence to Actelion seeking TRACLEER sample for use in bioequivalence testing. After Actelion refused to provide drug sample to Apotex and Roxane, “maintaining its right to choose with whom it does business” and citing certain REMS compliance issues, Apotex and Roxane allegedly threatened Actelion with antitrust litigation and with notifying the Federal Trade Commission (“FTC”). Instead of waiting for the other shoe to drop, Actelion took a proactive approach and sued the generic companies, saying that “Apotex and Roxane are seeking to force Actelion to supply them with product, turning well-settled law, not to mention basic free-market principles, on their head,” and that “Apotex’s and Roxane’s demands would also require Actelion to violate its regulatory obligations.”
In its Complaint, Actelion notes, among other things, that there is no provision in the FDC Act that the owner of a drug subject to an ETASU REMS is required to provide product sample upon the request of a potential generic competitor. Indeed, to the contrary, says Actelion, Congress twice rejected legislation to address the sale of product under a REMS to generic drug sponsors – once in 2007 when Congress was considering REMS legislation, and another time earlier this year when Congress was debating what provisions to include in the FDA Safety and Innovation Act (“FDASIA”).
As we previously reported, Section 1131 of the FDASIA bill as passed by the Senate would have amended FDC Act § 505-1 to state, among other things, that:
Notwithstanding any other provision of law, if a drug is a covered drug, no elements to ensure safe use shall prohibit, or be construed or applied to prohibit, supply of such drug to any eligible drug developer for the purpose of conducting testing necessary to support an application under [FDC Act § (b)(2) or § 505(j) or PHS Act § 351(k)] if the Secretary has issued a written notice described in paragraph (2), and the eligible drug developer has agreed to comply with the terms of the notice.
Even that language, which stopped short of requiring sale of a brand name drug to a generic competitor, was not enacted. Instead, current law merely states that “[n]o holder of an approved covered application shall use any element to assure safe use required by [FDA] under [FDC Act § 505-1(f)] to block or delay approval of an application under section 505(b)(2) or (j) or to prevent application of such element under [FDC Act § 505-1(i)(1)(B)] to a drug that is the subject of an [ANDA].”
FDA, for its part, has largely remained silent on the issues raised in the Actelion Complaint. In June 2009, Dr. Reddy’s Laboratories, Inc. submitted a citizen petition (Docket No. FDA-2009-P-0266) requesting that FDA “establish procedures to facilitate the availability of generic versions of drug products subject to a [REMS] and enforce the FDC Act to prevent companies from using REMS to block or delay generic competition.” FDA has not substantively responded to the petition.
FDA merely includes the following statement into REMS approval letters: “We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered application with elements to assure safe use from using any element to block or delay approval of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could result in enforcement action.” FDA does not comment on what sorts of actions the Agency might construe as use of an ETASU element to block or delay approval. FDA has also in at least one recent draft bioequivalence guidance stated, consistent with previous FDA-ANDA sponsor correspondence, that the Agency would be willing to notify the sponsor of the brand-name Reference Listed Drug (“RLD”) that the Agency has received sufficient assurance that the generic drug sponsor’s bioequivalence studies “will be conducted in such a manner as to ensure the safety of the subjects, and that the sponsor of the RLD may provide the sponsor of the BE studies or their agent with [sufficient drug product sample] for the purpose of conducting bioequivalence (including dissolution) testing.” Such language falls short of compelling sale. Absent Congress weighing in on the matter with legislation, debate over the next step in the process – supplying the product – will be an issue for the courts to address.