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Hatch-Waxman Litigation 101: The Orange Book and the Paragraph IV Notice Letter

Intellectual Property and Technology News

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The Hatch-Waxman Act sets forth the procedure for regulatory approval and commercial marketing of pharmaceuticals, including generic drugs.  Under the Act, a company can seek approval for a new branded drug, a generic version of a branded drug, or a hybrid of the two.  A New Drug Application (NDA) requires a robust set of safety and efficacy data.  An Abbreviated New Drug Application (ANDA), used for generic drugs, relies on safety and efficacy data of the reference drug.  A 505(b)(2) application used for new indications, dosage forms, or combinations relies on safety and efficacy data of the reference drug and must also provide additional bridging data to establish bioequivalence and/or bioavailability.

The Act includes incentives for both generic and branded companies. ANDA and 505(b)(2) filers can use the branded drug in bioequivalence/bioavailability testing to support their regulatory filings without threat of a patent infringement suit.  The first applicant to file an ANDA challenging the NDA holders’ patents is awarded 180 days of marketing exclusivity before any other generics will be allowed on the market.

Benefits to branded companies include data exclusivities and marketing exclusivities, such as new chemical entity, orphan drug and pediatric exclusivities. As part of the NDA, branded companies must submit to FDA a list of patents that cover the product.  This list includes patents that claim the drug substance (active ingredient), drug product (formulation and composition), and methods of use.1   Patents issued after NDA submission must be submitted to FDA within 30 days of issuance.  FDA publishes the list in the Approved Drug Products with Therapeutic Equivalence Evaluations, known as the Orange Book.2

Each ANDA must include a certification or statement for each patent listed in the Orange Book.  The certification may be under Paragraph II, the patent has expired; Paragraph III, the generic drug will not be approved until the patent expires; and/or Paragraph IV (PIV), applicant asserts the listed patent is invalid and/or will not be infringed. If there are no patents listed, applicant submits a Paragraph I certification.  If the Orange Book contains a method-of-use patent and the generic is seeking to exclude that indication from its approval, the ANDA must contain a Section viii statement.  This Section viii carveout allows the applicant to avoid litigating the relevant method-of-use patent.3

An ANDA applicant must notify both the patent owner and NDA holder of any PIV certification by sending a PIV notice letter describing the applicant’s invalidity and/or non-infringement arguments. The timing of the PIV notice letter is key: the applicant has 20 days to send the notice letter after receiving FDA’s acknowledgment that the ANDA has been received and is ready for substantive review.  The applicant cannot send the notice letter to the brand until it has received this acknowledgment.

Filing an ANDA with a PIV certification is an artificial act of infringement that allows the brand to file suit before the generic drug is commercialized.  Once both the patent owner and NDA holder have received the notice letter, they have 45 days to file suit.  If the brand sues within this 45-day window, it is entitled to an automatic 30-month stay of regulatory approval of the ANDA.  The 30-month stay begins on the “the later date of receipt” of the notice letter by the patent owner or NDA holder and is intended to give the brand and generic the necessary time to resolve the patent litigation.

The required contents of the notice letter include a detailed statement of the factual and legal bases of the applicant's invalidity, unenforceability, and/or non-infringement positions.  While the invalidity positions in the notice letter are not binding in subsequent litigation, they must be made in good faith and must be legally and scientifically vetted.  Failures to meet this standard have been factors supporting awards of attorneys and expert fees to the brand plaintiff. Notice letters, and the associated non-infringement and invalidity positions described therein, are not confidential.

If the notice letter contains non-infringement assertions, the applicant must also include an Offer of Confidential Access (OCA) to allow the brand an opportunity to evaluate the ANDA before filing suit to determine which patents to assert.  An applicant will typically draft the OCA to limit who may view the ANDA, prescribe the scope and length of any attendant prosecution bar, and identify which portions of the ANDA will be provided.  If the applicant does not provide an OCA, it forfeits the right to later file a declaratory judgment action for a declaration of noninfringement.  If the applicant makes an unreasonably restrictive offer and refuses to negotiate the terms of the OCA, the brand may not be precluded from asserting infringement despite lack of sufficient information to evaluate infringement.

These are a few of the key issues that must be addressed before a Hatch-Waxman suit is filed. To learn more about these issues, please contact either of the authors.


1 21 U.S.C. § 355(b)(1); 21 C.F.R. § 314.53(b)(1).

2 21 U.S.C. § 355(b)(1), (c)(2); 21 C.F.R. § 314.53(e).

3 21 C.F.R. § 314.95(a)(3).