Requirements, Benefits, And Possible Consequences Of Listing Patents In FDA's Orange Book


The Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman Act) amended patent law and drug law to facilitate pharmaceutical development and encourage the marketing of generic pharmaceuticals. Pub. L. No. 98-417, 98 Stat. 1585 (amending 21 U.S.C. § 355); see also H.R. Rep. No. 98-857, pt. 1, at 1 (1984), reprinted in 1984 U.S.C.C.A.N. 2647, 2647. While the Hatch-Waxman Act has been amended several times, the general framework remains the same. Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Pub. L. No. 108-173, 117 Stat. 2066; 21st Century Cures Act of 2016, Pub. L. No. 114-255, 130 Stat. 1033. Under the Hatch-Waxman Act, the U.S. Food and Drug Administration (FDA) approves drug products through three types of applications: (1) new drug applications (NDAs), which must include full reports of nonclinical and clinical investigations showing that the proposed drug is safe and effective; (2) 505(b)(2) NDAs, which contain full reports of safety and effectiveness, where at least some of the information required for approval comes from studies by others; and (3) abbreviated new drug applications (ANDAs), which must contain information showing that the proposed drug, among other things, is bioequivalent to the reference drug.

NDAs must be accompanied by certain patent information, which the FDA then lists in its Approved Drug Products with Therapeutic Equivalence Evaluations publication (known as the Orange Book). Having patent information listed in the FDA's Orange Book provides benefits of possible regulatory stays under the Hatch-Waxman Act, which protect NDA holders from harm that could otherwise result from FDA approval of an infringing drug product. Not all patent information should be listed, however, and pharmaceutical companies should consider the statutory and regulatory requirements for listing, as well as the possible consequences of improper listing.

Patent Information for Listing

Information That 'Must' Be Submitted NDA applicants "shall file with the application the patent number and the expiration date of any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug." 21 U.S.C. § 355(b)(1); see also 21 C.F.R. § 314.53(b)(1) (construing "drug" as "drug product"), (d)(1). If a patent issues after the NDA is filed but before it is approved, "the applicant shall amend the application to include the information." 21 U.S.C. § 355(b)(1); see also 21 C.F.R. § 314.53(d)(1) (providing a deadline of within 30 days of patent issuance). For patents issued after approval of the NDA, the NDA "holder shall file such information . . . not later than thirty days after the date the patent involved is issued." 21 U.S.C. § 355(c)(2); see also 21 C.F.R. § 314.53(d)(3).

The FDA publishes the submitted patent information in the Orange Book. 21 U.S.C. § 355(b)(1), (c)(2); 21 C.F.R. § 314.53(e). The FDA takes the position that it will not substantively review the correctness of patent information before publishing because the FDA interprets its role in listing patent information as "purely ministerial" and has explained that it "lacks both the resources and the expertise to police the correctness . . . of every patent listing submitted by an NDA holder." aaiPharma Inc. v. Thompson, 296 F.3d 227, 237 (4th Cir. 2002); see also United Food & Commercial Workers Unions & Emp'rs Midwest Health Benefits Fund v. Novartis Pharm. Corp., No. 15-cv-12732, 2017 BL 228218, at *8 (D. Mass. June 30, 2017); Teva Pharm., USA, Inc. v. Leavitt, 548 F.3d 103, 106 (D.C. Cir. 2008); Am. Bioscience, Inc. v. Thompson, 269 F.3d 1077, 1080 (D.C. Cir. 2001).

The FDA regulations indicate that patents whose information "must" be submitted "consist of drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method-of-use patents." 21 C.F.R. § 314.53(b)(1). Drug substance patents include those "that claim the drug substance that is the subject of the pending or approved NDA or that claim a drug substance that is the same as the active ingredient that is the subject of the approved or pending NDA." Id.; see also 67 Fed. Reg. 65,448, 65,452 (Oct. 24, 2002) explaining that an applicant "would determine whether the drug substance was the same as the active ingredient . . . by considering whether the drug substances can be expected to perform the same with respect to such characteristics as dissolution, solubility, and bioavailability"). "For patents that claim only a polymorph that is the same as the active ingredient described in the approved or pending NDA, the applicant must certify in the required FDA declaration form that the applicant has test data . . . demonstrating that a drug product containing the polymorph will perform the same as the drug product described in the NDA." 21 C.F.R. § 314.53(b)(1).

Drug product patents include those "that claim the drug product . . . that is described in the pending or approved NDA." Id. (citing 21 C.F.R. § 314.3). FDA regulations define "drug product" as "a finished dosage form, e.g., tablet, capsule, or solution, that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients." Id. § 314.3(b). In interpreting the regulations, the FDA noted that dosage forms listed in the Orange Book include "metered aerosols, capsules, metered sprays, gels, and pre-filled drug delivery systems." 68 Fed. Reg. 36,675, 36,680 (June 18, 2003)." The key factor is whether the patent being submitted claims the finished dosage form of the approved drug product." Id.

Method-of-use patents include those "that claim indications or other conditions of use for which approval is sought or has been granted in the NDA." 21 C.F.R. § 314.53(b)(1). "The applicant must separately...

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