FDA PROPOSAL TO AMEND REGULATIONS PERTAINING TO GENERIC DRUG PRODUCTS
On August 6, 1999, the Food and Drug Administration (FDA) proposed to amend its current regulations governing the 180-day market exclusivity that is granted to certain generic drug products.[1] This proposed rule represents a significant change to the current landscape of drug exclusivity. This Alert provides background information on the generic drug approval process and patent notification, and a summary of the proposed 180-day exclusivity regulations. The deadline for public comment on this proposed rule is November 4, 1999.
ANDA Approval and Patent Notification
The Drug Price Competition and Patent Term Restoration Act of 1984 (Waxman-Hatch Act) amended the Federal Food, Drug, and Cosmetic Act (FFDCA), dramatically changing existing drug approval laws. The Waxman-Hatch Act codified the process for approval of generic drugs, allowing for approval of a generic copy of a previously approved "pioneer" drug product without the submission of a full New Drug Application (NDA). This process involves submission of an Abbreviated New Drug Application (ANDA) that relies upon FDA approval of the pioneer drug to demonstrate safety and effectiveness. Generally, the ANDA need only establish that the generic drug is bioequivalent to the pioneer drug (i.e. the reference-listed drug for which therapeutic equivalence is sought).
Each NDA must include information about patents that are applicable to the drug product. These patents are listed in the Approved Drug Products with Therapeutic Equivalence Evaluations (The Orange Book). An ANDA must include one of four statutory certifications for each patent in the pioneer drug's NDA: 1) that no patent is listed for the pioneer drug; 2) that such patent has expired; 3) the date on which the patent will expire; or 4) that such patent is invalid or not infringed.[2] These certifications are referred to as "paragraph I" through "paragraph IV" certifications respectively.[3]
If an ANDA contains a paragraph IV certification, the applicant must notify the pioneer drug NDA holder, as well as the appropriate patent holder, if different, that the application has been submitted. Under the Waxman-Hatch Act this notice provides the NDA holder or patent holder with the right to sue for patent infringement. If a suit is brought within 45 days of receipt of notice of the paragraph IV certification, approval of the ANDA will be stayed for 30 months, or until the patent is found to be invalid or not infringed, whichever comes first.
180-Day Exclusivity
In order to encourage generic drug manufacturers to challenge invalid or not-infringed patents, the Waxman-Hatch Act provides, in some circumstances, 180 days of market exclusivity to the first applicant to file an ANDA with a paragraph IV certification. The Act provides that once a substantially complete ANDA with a paragraph IV certification is submitted, any subsequent ANDA for the same drug drug[4] that also has a paragraph IV certification cannot be approved until 180 days after either 1) the first commercial marketing of the drug, or 2) a court decision that finds the patent in question to be invalid or not infringed, whichever comes first.
In 1994 FDA promulgated regulations implementing the 180-day exclusivity and other provisions of the Waxman- Hatch Act.[5] These regulations, found at 21 C.F.R. § 314.107, added an additional requirement not found in the statute: that before 180-day exclusivity could be granted, the ANDA applicant must first be sued by the NDA holder or patent holder and then must "successfully defend" a patent suit. However, two U.S. Court of Appeals decisions struck down FDA's "successful defense" regulation, finding that Congress did not intend such a requirement when it enacted the Waxman-Hatch Act.[6]
As a result of these court decisions, FDA revoked its "successful defense" requirement, and has been applying the terms of the statute to decisions on 180-day exclusivity on a case-by-case basis. The statutory 180-day exclusivity provisions, without any interpretive regulations, have created uncertainty about the operation of the exclusivity period, and allow instances where application of the statute could delay approval of subsequent generic products for far longer than 180 days. For example, if the generic pharmaceutical firm that files the first ANDA receives FDA approval but is unable to bring its product to market, there is no commercial marketing to start the 180-day exclusivity period. Such a situation could potentially block approval of subsequent ANDAs. Such a situation could arise because of technical or financial difficulties on the part of the generic firm prohibiting it from marketing its product. Alternatively, marketing could be delayed due to agreement between the generic and pioneer drug firms not to market the drug. Both situations have the potential to produce results that may be considered contrary to the congressional intent of the Waxman-Hatch Act, which is (in part) to benefit consumers by encouraging the entry of generic drugs onto the market.
Proposed Rule
FDA's proposed 180-day exclusivity regulations represent an effort by the agency to address defects in the current process.
The key provision of the proposed regulations is the creation of a "180-day triggering period."[7] This triggering period (distinct from the 180-day exclusivity period) would provide a time limit during which there must either be a court decision finding the patent in question to be invalid or not infringed, or the first ANDA applicant must begin commercial marketing of the drug. If neither of the two "triggering events" occurs within the triggering period, the first ANDA applicant would lose its eligibility for 180-day exclusivity. The 180-day triggering period would generally start when FDA finds an ANDA from a subsequent applicant to be approvable, were it not for the first ANDA applicant's exclusivity. Thus, the manufacturer with the first approved generic drug cannot block subsequent ANDA approvals by not marketing its product.
The proposed regulations provide several exceptions to the general rule that the 180-day triggering period starts when a subsequent ANDA is approvable. The beginning of the triggering period could be delayed by any of the following situations:
- The first ANDA applicant is sued by the NDA holder or patent holder, and the ANDA is blocked from approval by the statutory 30-month stay
- A court enjoins the marketing of the drug
- The pioneer drug is still the subject of an existing exclusivity period.
Once the above-listed conditions are removed or lifted, the 180-day triggering period could begin.
Although the 180-day triggering period is the most significant element, the proposed regulations also address several other long-standing issues regarding 180-day exclusivity:
- Only the first ANDA applicant to file a paragraph IV certification would be eligible for exclusivity. If the applicant, for any reason, withdraws the application or changes the certification, it would no longer be eligible for exclusivity, and no subsequent ANDA applicant would be eligible to receive the 180-day exclusivity
- The proposed regulations make clear that the ANDA applicant need not be sued for patent infringement in order to receive exclusivity
- If an ANDA applicant is sued, and loses its suit, no ANDA applicant is eligible for exclusivity.
- FDA proposes to define the term "decision of a court." One of the two triggering events in the statute is "a decision of a court ... holding the patent which is the subject of the certification to be invalid or not infringed." The exact meaning of this phrase has been the subject of some controversy. FDA proposes to define the term as "a final court decision finding the patent to be invalid, unenforceable, or not infringed, resulting from patent litigation brought against the first applicant or any subsequent applicant [emphasis added]. This includes a final court decision in a declaratory judgment action finding the patent to be invalid, unenforceable, or not infringed."[8] Under this proposed definition, a decision in a suit against subsequent ANDA applicants would be sufficient to trigger exclusivity.
- Under the proposed definition of "decision of a court," a court must affirmatively find that the patent is invalid, unenforceable or not infringed before exclusivity is triggered; dismissal of the case on other grounds would not be sufficient to constitute a "decision of a court."[9]
The proposed rule on 180-day exclusivity represents FDA's initial attempt to address defects in the current regulations, and is certainly not the final word on this complex issue. As with other FDA rulemakings, interested parties are encouraged to file written comments on the proposed rules with the agency. The deadline for comments is November 4, 1999.
[1] 64 FR 42873 (August 6, 1999).
[2] FDA regulations are slightly different from the statute, adding the term "unenforceable" to invalid or not infringed. 21 C.F.R. § 314.107(b)(1).
[3] Only ANDAs with paragraph IV certifications are relevant to the current discussion. If an ANDA is submitted with a paragraph I or paragraph II certification, it can be approved by FDA immediately if all other approval conditions are met. If an ANDA is submitted with a paragraph III certification, FDA cannot approve that application until after the patent(s) in question expire(s).
[4] FDA considers each dosage form of a drug to be a different drug product for purposes of 180-day exclusivity. See 64 FR at 42881.
[5] 59 FR 50338 (October 3, 1994).
[6] Mova Pharmaceuticals, Inc. v. Shalala, 140 F.3d 1060 (D.C. Cir. 1998); Granutec, Inc. v. Shalala, 1998 U.S. App. Lexis 6685 (4th Cir. Apr. 3, 1998).
[7] FDA is also accepting comments on a 60-day triggering period and is considering a shorter triggering period in certain situations.
[8] Proposed 21 C.F.R. § 314.107(a)(2), 64 FR at 42885.
[9] The current proposed rule appears to address the deficiencies in FDA's previous position on the matter that was successfully challenged by an ANDA applicant in Teva Pharmaceuticals v. United States Food and Drug Administration, 182 F.3d 1003, (D.C. Cir. 1999).