Final FDA Rule Clarifies Pharma Patent Process With Aim of Reducing Unnecessary Litigation

Regulatory NewsRegulatory News | 05 October 2016 |  By 

With the intent to cut back on the type of litigation that can delay the approval and marketing of generic drugs under 505(b)(2) applications and abbreviated new drug applications (ANDAs), the US Food and Drug Administration (FDA) on Wednesday released a final rule that revises and clarifies its regulations on a number of different parts of the pharmaceutical patent process.

The 289-page final rule amends FDA’s regulations to facilitate better compliance with and enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which is the over-arching legislation that gives FDA its authority to regulate and oversee food, drugs and cosmetics. A couple key highlights include:

  • Establishing a 30-day timeframe in which the new drug application (NDA) holder will be required to substantively respond to the patent listing dispute and verify the accuracy and completeness of the response.
  • Establishing a date (the first working day after the day the patent is published in the Orange Book) before which an ANDA applicant cannot send valid notice of a paragraph IV certification to a newly listed patent. Notice of a paragraph IV certification that has been sent prematurely is invalid, FDA says, noting the new approach is intended to promote equity among ANDA applicants seeking eligibility for 180-day exclusivity.
  • Eliminating the use of serial submissions of amendments and multiple notices of paragraph IV certifications, which FDA says are “overly burdensome to FDA and NDA holders. Such a practice makes it difficult to determine which paragraph IV certification and notice of paragraph IV certification is valid.”
  • Revising requirements related to the submission of patent information on: (1) Patents that claim the drug substance and/or drug product and meet the requirements for patent listing on that basis; (2) drug substance patents that claim only a polymorph of the active ingredient; and (3) certain NDA supplements.
  • Delineating the two limitations on the timeframe within which notice of a paragraph IV certification can be provided to the NDA holder and each patent owner: (1) The date before which notice may not be given (reflecting FDA’s longstanding practice regarding premature notice) and (2) the date, established by MMA, by which notice must be given to be considered timely.

Kurt Karst, a director and counsel at Hyman, Phelps & McNamara, told Focus: “FDA has described it as clarifications, which is true to some extent. It clarifies policies that have been in effect, and actually writes them down. That being said, this is a pretty significant re-write of the regulations. It’s a lot of small clarifications adding up to a lot.”

A significant number of pages of the final rule focus on clarifying requirements for the NDA holder’s description of the specific approved method of use claimed by a patent (the “use code”) required for publication in FDA’s Orange Book “to address overbroad or ambiguous use codes that may delay approval of generic drugs.”

This clarification is intended to better implement statutory provisions that permit 505(b)(2) and ANDA applicants to omit (or “carve out”) protected conditions of use from labeling and obtain approval for conditions of use that are not covered by unexpired patents or exclusivity.


The final rule implements portions of Title XI of the Medicare Modernization Act (MMA) that pertain to:

  • the notice sent to each patent owner and the new drug application (NDA) holder of certain patent certifications made by applicants submitting 505(b)(2) applications or ANDAs.
  • the availability of 30-month stays of approval on 505(b)(2) applications and ANDAs that are otherwise ready to be approved.
  • submission of amendments and supplements to 505(b)(2) applications and ANDAs.
  • the types of bioavailability and bioequivalence data that can be used to support these applications.

On 6 February 2015, FDA published a proposed rule to implement these portions of the MMA that pertain to 30-month stays and other matters not related to forfeiture of 180-day exclusivity, and make regulations governing 505(b)(2) applications and ANDAs consistent with the MMA’s amendments to the FD&C Act.

FDA received 13 comments from pharmaceutical industry associations, brand and generic drug manufacturers, law firms and a law student. Based on the comments, FDA says it’s finalizing the proposed rule with certain revisions and technical amendments, nearly all of which are explained in Wednesday’s text.

Use Code Changes

In terms of the clarifying revisions to the regulations and how it will improve the accuracy of use codes (the specific approved method of use claimed by the patent), FDA notes three general principles clarifying the revisions to the regulations regarding the content of use codes:

  • The use code must only describe a patented method of use that is described in FDA-approved product labeling. If the method of use claimed by the patent uses different terminology than the approved labeling and/or is broader than an indication or other approved condition of use, then the use code would need to be phrased more narrowly than the patent claim to only describe the specific patented method of use.
  • Patented method of use is co-extensive with an indication or other approved condition of use: The use code must describe only the specific approved method of use claimed by the patent.
  • Patented method of use is narrower than an indication or other approved condition of use: If the method of use claimed by the patent does not cover an indication or other approved condition of use in its entirety, then the NDA holder must describe only the specific approved method of use claimed by the patent--not the broader indication or other approved condition of use that may include, but is broader than, the use claimed by the patent.


For patent listing disputes, FDA is now requiring that the patent listing dispute communication to contain a statement of dispute that “describes the specific grounds for disagreement regarding the accuracy or relevance of patent information for FDA to send to the applicable NDA holder. If a person disputes the accuracy or relevance of submitted patent information regarding an approved method of using the drug product, this statement of dispute must be only a narrative description (no more than 250 words) of the person’s interpretation of the scope of the patent with respect to the method of use.”

But as far as the limited circumstances in which FDA would “defer to the 505(b)(2) or ANDA applicant’s interpretation of the scope of a patent that it does not own,” FDA says it believes it has the authority to establish such a regulation but it’s not finalizing such an approach and is instead taking an incremental approach.

“If these revisions to our regulations do not adequately address the problem, we will further consider whether to finalize the proposal to review a proposed labeling carve-out for a 505(b)(2) application or ANDA with deference to the 505(b)(2) and/or ANDA applicant(s)’ interpretation of the scope of the patent,” the agency adds.
Hyman, Phelps & McNamara’s Karst explained to Focus that this deference to a specific applicant would have been a “massive shift” and FDA “knew it was setting itself up for litigation as it would be such a shift in approach.”

“So now we’ve got this new almost a hybrid procedure and we’ll see how it works in practice,” he added.

A 'Wrench' in Generic Approvals

FDA offers a few examples on the use code revisions, noting that as the US Supreme Court said in one case: “An overbroad use code… throws a wrench into the FDA’s ability to approve generic drugs as the statute contemplates.”

One example is for Prandin (repaglinide) tablets, which currently are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and US Patent No. 6,677,358 (ʼ358 patent) was listed in the Orange Book as claiming a method of using Prandin.

In Novo Nordisk A/S v. Caraco Pharm. Labs., the Federal Circuit explained that claim 4 of the ʼ358 patent “claims ‘[a] method for treating non-insulin dependent diabetes mellitus (NIDDM) comprising administering to a patient in need of such treatment repaglinide in combination with metformin.’ … An appropriate use code therefore must be limited to use of ‘repaglinide in combination with metformin’ to treat NIDDM.” And FDA says a “similar approach would apply if the patented method of use is described in a section of labeling other than Indications and Usage. 

“For example, if the patent claims a novel dosing regimen for a particular indication, the use code must specifically describe the protected dosing regimen for that indication and not only the indication to which the dosing regimen relates. Thus, if the method(s) of use claimed by the patent does not cover an indication or other approved condition of use in its entirety, an NDA holder’s submission of a use code that describes an entire indication or other approved condition of use would violate FDA’s regulations,” FDA says.

FDA Final Rule implementing portions of Title XI of the MMA and revising and clarifying FDA regulations relating to 505(b)(2) applications and ANDAs


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