A Primer on Paragraph IV Certifications: Into the Belly of the Hatch-Waxman Beast Part 1

In a moment of extreme weakness, I agreed to Gene’s request to doing a primer on Paragraph IV Certifications under the Drug Price Competition and Patent Term Restoration Act, commonly referred to as Hatch-Waxman.  I don’t know if you would call me an expert, but I’ve studied many, many cases involving Paragraph IV Certifications under Hatch-Waxman.  The courts have found Hatch-Waxman to be a hydra-like monster with a labyrinth of sections that are frequently confusing (or worse yet, conflicting).  Paragraph IV Certifications are a particular trouble spot in Hatch-Waxman.  So if you’re up to diving into the “belly of this beast,” let’s examine the characteristics of this most infamous of the Hatch-Waxman monsters.

To understand Paragraph IV Certifications, you must first address what an Abbreviated New Drug Application (ANDA) is.  ANDAs are how generic drug manufactures expedite the approval of their generic drugs.  To use the language of the Federal Circuit, “[g]eneric drug companies are not required to conduct their own independent clinical trials to prove safety and efficacy, but can instead rely on the research of the pioneer pharmaceutical companies.”  See the 2008 Federal Circuit case of Janssen Pharmaceutica, N.V. v. Apotex, Inc.[1] which provides an excellent explanation of what the ANDA and Paragraph IV certification process is all about.  Instead, in the ANDA process, the generic drug company may rely upon this clinical safety and efficacy of the “pioneer pharmaceutical company” if it can “show show bioequivalence of its generic drug to the NDA drug.”  “Bioequivalence” is defined by the FDA as “the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.”[2]  I’ll get to where those “pioneer pharmaceutical companies” and “NDA drugs” enter the ANDA approval process next.

Before you can have an ANDA for approving a generic drug, you must first have a New Drug Application or NDA.  The NDA is how “a pioneering or brand name drug company seeking to manufacture a new drug must prepare, file, and have approved” its drug by the FDA.[3]  As part of the NDA process, the “pioneering drug company” (NDA applicant) must submit the above mentioned information on the new drug’s safety and efficacy obtained from clinical trials.”[4]  The NDA applicant must also identify all patents that “could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug,”[5]  The patents covering approved drug (or use thereof) are published in what’s called the FDA’s “Orange Book.”


When seeking approval of an ANDA, and if there is a patented drug (or patented use of a drug) involved that’s listed in the “Orange Book,” a generic drug maker must make one of four types of patent certifications.[6]  (More on the problems of how those patents covering the drug or use thereof are listed in the FDA’s “Orange Book” later when I get to “use code” issues.)  Of these patent certifications, the Paragraph IV Certification has been acknowledged to be the most difficult to administer.[7]  Briefly, in making a Paragraph IV Certification, the generic drug maker says the patent is at least one of the following:  (1) invalid; (2) not infringed; or (3) unenforceable.[8]  That’s the Reader’s Digest version on the requirements for a Paragraph IV Certification; after that, the story gets much more complicated and adversarial.

Even though the generic drug maker does not and, in fact, cannot market the drug prior to approval of the ANDA, the filing of a Paragraph IV Certification is nonetheless treated as a technical act of patent infringement.[9]  The generic drug maker must also provide notice to both the owner of the patented drug (or patented use thereof) and the NDA holder[10] “of the factual and legal bases for the Paragraph IV Certification.”[11]  Upon such notice, the patent owner/NDA holder “have the option of suing on all, some, or none of the patents included in the Paragraph IV Certification.”[12]  If the patent owner does not bring suit within 45 days of receiving such notice, the “FDA may issue final approval of the ANDA once its approval requirements have been satisfied.”[13]  But if the suit is brought by the patent owner/NDA holder within this 45 day period, the “FDA may not approve the ANDA for 30 months.”[14]  After that 30 month period, or if the patents involved are deemed invalid or not infringed (whichever occurs sooner), the FDA may then approve the ANDA of the generic drug maker.[15]

To incentivize generic drug makers to “challenge suspect Orange Book listed patents,” Hatch-Waxman gives the first such filer of a Paragraph IV Certification a marketing “bonus”:  a “180-day period of generic marketing exclusivity during which time [the] FDA will not approve” a later filed ANDA based on a Paragraph IV Certification based on the same NDA.[16]  Even more interesting, this first Paragraph IV Certification ANDA filer is entitled to this 180-day marketing exclusivity period “regardless of whether it establishes that the Orange Book patents are invalid or not infringed by the drug described in its ANDA.”[17]  Similar to when the ANDA approval process starts, the start of this 180-day marketing exclusivity period is triggered by either the commercial marketing of the drug by this first Paragraph IV Certification ANDA filer or by a court decision that the patent on the drug is not infringed or is invalid.[18]  While only the first Paragraph IV Certification ANDA filer can get this 180-day marketing exclusivity period, subsequent Paragraph IV Certification ANDA filers can still trigger the beginning of this period of marketing exclusivity by getting successful court judgments of noninfringement and/or invalidity.[19]

In 2003, Congress amended Hatch-Waxman in response to “NDA holders using several methods for delaying early resolution of patent disputes.”[20]  One such amendment was allowing the Paragraph IV Certification ANDA filer to bring a declaratory judgment action for noninfringement and/or invalidity under 28 U.S.C. § 2201 against the patent owner/NDA holder if no infringement action was brought by the patent owner/NDA holder within the 45-day notice period.[21]  Also in response to such delay tactics by patent owner/NDA holders, Congress additionally created in this 2003 amendatory legislation a statutory counterclaim for generic drug makers to force the patent owner/NDA holder to “correct or delete” patent information that it submitted under 21 U.S.C. § 355(b)or(c) “on the ground that the patent does not claim   .   .   .  an approved method of using the drug.”  One such “correct[ion] or delet[ion]” that the generic drug maker may request relates to the submission of proper “use codes”[22] by the patent owner/NDA holder that are important when the generic drug maker requests approval by the FDA of what is called a “carve out” label of the approved drug, but for an non-patented use.[23]

Not surprisingly, Paragraph IV Certifications under Hatch-Waxman have spawned a tremendous number of legal conflicts between the generic drug makers and the owners of those patented drugs (or patented uses of those drugs).[24]  You would also think that most of the potential “ambiguities” of Hatch-Waxman relating to Paragraph IV certifications have been dealt with (many have).  But every once and awhile the Hatch-Waxman Paragraph IV Certification “hydra” reveals a new wrinkle that previously lay “sleeping.”  I’ll address some of those new wrinkles, especially the latest flurry of Hatch-Waxman “carve out” cases (including the decision by the Supreme Court in the 2012 case of Caraco Pharmaceutical Laboratories v. Novo Nordisk AS on enforcement of proper “use codes” for such “carve outs”), as well as the Hatch-Waxman “reverse payment” cases (now squarely before the Supreme Court in FTC v. Watson Pharmaceuticals which recently heard oral argument in this case) in my next installment on the “wild and woolly world” of Paragraph IV Certifications.


[1] 540 F.3d 1353 (Fed. Cir. 2008).

[2] See 21 CFR § 320.1.

[3] 21 U.S.C. §§ 355(a)&(b) (quoting from Janssen Pharmaceutica).

[4] 21 U.S.C. § 355(b(1) (quoting from Janssen Pharmaceutica).

[5] 21 U.S.C. §§ 355(b)(1)&(c)(1) (quoting from Janssen Pharmaceutica).


[7] See Allen, “When Does the Clock Begin Ticking?:  Interaction of the Hatch-Waxman Act 180-Day Generic Abbreviated New Drug Application and Food and Drug Administration Modernization Act Pediatric Exclusivity Provisions-A Significant Issue in Eli Lilly & Co. v. Barr Laboratories, Inc.,” Aipla Quarterly J., Vol. 30 (No. 1) (Winter 2002), p. 9.

[8] See Glover, “Regulatory Concerns & Market Exclusivity,” 1175 PLI/Corp (May 2000), p. 638, 643.

[9]35 U.S.C. § 271(e)(2)(A).

[10] The patentee owner and NDA holder are usually one and the same, but need not be the same.

[11]  21 U.S.C. § 355(j)(2)(B) (quoting from Janssen Pharmaceutica).

[12] (quoting from Janssen Pharmaceutica).

[13]  21 U.S.C. § 355(j)(5)(B)(iii) (quoting from Janssen Pharmaceutica).

[14]  21 U.S.C. § 355(j)(5)(B)(iii) (quoting from Janssen Pharmaceutica).

[15]  21 U.S.C. § 355(j)(5)(B)(iii) (paraphrasing Janssen Pharmaceutica).

[16]  21 U.S.C. § 355(j)(5)(B)(iv) (quoting Janssen Pharmaceutica).  See also Minnesota Mining & Mfg. Co. v. Barr Laboratories, Inc., 289 F.3d 775, 778 (Fed. Cir. 2002).

[17]  21 U.S.C. § 355(j)(5)(B)(iv)(II)(bb) (quoting Janssen Pharmaceutica).

[18]  21 U.S.C. § 355(j)(5)(B)(iv) (paraphrasing Janssen Pharmaceutica).

[19]  21 U.S.C. § 355(j)(5)(B)(iv) (paraphrasing Janssen Pharmaceutica which cited to the Barr Labs case.

[20] (quoting Janssen Pharmaceutica).

[21] 21 U.S.C. § 355(j)(5)(C) (quoting Janssen Pharmaceutica).

[22] See 21 CFR §§ 314.53(c)(2)(ii)(P)(3), (e).  As noted by the U.S. Supreme Court in Caraco Pharmaceutical Laboratories v. Novo Nordisk AS, the FDA does not attempt to verify the accuracy of such use codes.  See page 1 of slip opinion.

[23] See Caraco Pharmaceutical Laboratories v. Novo Nordisk AS (Sup. Ct. 2012), slip opinion at pp. 1-7.

[24] One of the more bizarre and peculiar jurisdictional “conflicts” occurred in Minnesota Mining & Mfg. Co. v. Barr Laboratories, Inc. 289 F.3d 775 (Fed. Cir. 2002) (hereafter referred to as the “Barr Labs” case).  In the Barr Labs case, the Federal Circuit not only had to determine when the ANDA approval process began, but more importantly, who determined when that process began.  On the one hand, the majority opinion in 3M said the generic drug maker could seek such resolution only from the FDA under the Administrative Procedure Act (APA), and not by direct court action.  On the other hand, the majority opinion also affirmed the district court’s ruling that the patentee’s (3M’s) infringement action under 35 U.S.C. § 271(e)(2)(A) should be dismissed with prejudice.  The odd and inconsistent positions taken by the majority opinion in the Barr Labs case were not lost on Judge Gajarsa, who concurred in judgment only, poignantly observing that:“[i]t is inconsistent to say that the trial court did not abuse its discretion in finding the notice sufficient in a non-APA action and thereby dismissing the action with prejudice, and then to conclude that the sufficiency of notice cannot be considered outside the context of the APA.”  Judge Garjasa was even more blunt about the procedural nightmare that the majority opinion in Barr Labs had created:  “[t]he majority fails to address the key issues in this appeal and adds an entire layer of administrative complexity to create a sizeable procedural Gordian knot.”  Indeed, as pointed out by Judge Gajarsa, the FDA appeared to have said that sufficiency of such notice is not an issue they (the FDA) could/would resolve.  Indeed, Judge Lourie later wrote a vigorous dissent (joined by Judge Gajarsa) from a denial of a request for rehearing en banc of the three-judge panel decision in the Barr Labs case.


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