Adieu, “Orange Book FR Safety or Effectiveness Determinations List”; Hello, “Orange Book Patent Listing Dispute List”

The Orange Book has undergone – and continues to undergo – a lot of change as a result of FDA’s October 2016 promulgation of final regulations (effective as of December 5, 2016) to implement parts of the December 8, 2003 Medicare Modernization Act (“MMA”).  We pointed out some of those changes in our annual review of the Orange Book (see our previous post here), as well as in a subsequent post on changes made to the Orange Book reflecting new FDA guidance, titled “Referencing Approved Drug Products in ANDA Submissions.”  Most recently, we delved into the new “Reference Listed Drugs by ANDA Reference Standard List” (see our previous post here), which is intended to “assist applicants submitting an ANDA to seek approval of a generic drug in identifying an RLD when an ANDA [Reference Standard] has been selected.”  Last week, we became aware of some additional changes to the Orange Book . . . and one in particular that we had been waiting for.

First, FDA has discontinued publishing the “FR Notice Determination of Safety or Effectiveness List.” (The “FR” in the title is short for “Federal Register.”)  FDA had published the list for many years (most recently in December 2016), and it was a helpful resource to determine what withdrawn drug products were the subject of an FDA determination (since 1995) that withdrawal was not for reasons of safety or efficacy.  (Although the Orange Book continues to include the standard ““**Federal Register determination that product was not discontinued or withdrawn for safety or efficacy  reasons**” next to a particular discontinued drug product, the “FR Notice Determination of Safety or Effectiveness List” included additional details about each discontinued drug product.)  Now, the website that housed that list simply states “This list is no longer published,” and refers readers to the new “Reference Listed Drugs by ANDA Reference Standard List” (see here).

Second, and of greater interest to Orange Book followers, is the new “Orange Book Patent Listing Dispute List.” The list implements FDA’s new method-of-use patent/patent use code patent challenge regulations and fulfills FDA’s new requirement to “promptly post information on its Web site regarding whether a patent listing dispute has been submitted for a published description of a patented method of use for a drug product and whether the NDA holder has timely responded to the patent listing dispute.”  The new patent challenge procedures are laid out at 21 C.F.R. § 314.53(f)(1) and state:

(f) Correction of patent information errors—(1) Requests by persons other than the NDA holder. If any person disputes the accuracy or relevance of patent information submitted to the Agency under this section and published by FDA in the list, or believes that an NDA holder has failed to submit required patent information, that person must first notify the Agency in a written or electronic communication titled “314.53(f) Patent Listing Dispute.” The patent listing dispute communication must include 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. For a dispute regarding the accuracy or relevance of 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. This statement of dispute must only contain information for which the person consents to disclosure because FDA will send the text of the statement to the applicable NDA holder without review or redaction. The patent listing dispute communication should be directed to the Office of Generic Drugs, OGD Document Room, Attention: Orange Book Staff, 7620 Standish Pl., Rockville, MD 20855, or to the Orange Book Staff at the email address listed on the Agency’s Web site at http://www.fda.gov.

(i) Communication with the NDA holder—(A) Drug substance or drug product claim. For requests submitted under this paragraph (f)(1) that are directed to the accuracy or relevance of submitted patent information regarding a drug substance or drug product claim, the Agency will send the statement of dispute to the applicable NDA holder. The NDA holder must confirm the correctness of the patent information and include the signed verification required by paragraph (c)(2)(ii)(R) of this section or withdraw or amend the patent information in accordance with paragraph (f)(2) of this section within 30 days of the date on which the Agency sends the statement of dispute. Unless the NDA holder withdraws or amends its patent information in response to the patent listing dispute, the Agency will not change the patent information in the Orange Book.

(B) Method-of-use claim. For requests submitted under this paragraph (f)(1) that are directed to the accuracy or relevance of submitted patent information regarding an approved method of using the drug product, FDA will send the statement of dispute to the NDA holder. The NDA holder must confirm the correctness of its description of the approved method of use claimed by the patent that has been included as the “Use Code” in the Orange Book, or withdraw or amend the patent information in accordance with paragraph (f)(2) of this section, provide a narrative description (no more than 250 words) of the NDA holder’s interpretation of the scope of the patent that explains why the existing or amended “Use Code” describes only the specific approved method of use claimed by the patent for which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture, use, or sale of the drug product, and include the signed verification required by paragraph (c)(2)(ii)(R) of this section within 30 days of the date on which the Agency sends the statement of dispute. The narrative description must only contain information for which the NDA holder consents to disclosure because FDA will send the text of the statement to the person who submitted the patent listing dispute without review or redaction.

(1) If the NDA holder confirms the correctness of the patent information, provides the narrative description required by paragraph (f)(1)(i)(B) of this section, and includes the signed verification required by paragraph (c)(2)(ii)(R) of this section within 30 days of the date on which the Agency sends the statement of dispute, the Agency will not change the patent information in the Orange Book.

(2) If the NDA holder responds to the patent listing dispute with amended patent information in accordance with paragraph (f)(2) of this section, provides the narrative description required by paragraph (f)(1)(i)(B) of this section, and includes the signed verification required by paragraph (c)(2)(ii)(R) of this section within 30 days of the date on which the Agency sends the statement of dispute, FDA will update the Orange Book to reflect the amended patent information.

(ii) Patent certification or statement during and after patent listing dispute. A 505(b)(2) application or ANDA must contain an appropriate certification or statement for each listed patent, including the disputed patent, during and after the patent listing dispute.

(iii) Information on patent listing disputes. FDA will promptly post information on its Web site regarding whether a patent listing dispute has been submitted for a published description of a patented method of use for a drug product and whether the NDA holder has timely responded to the patent listing dispute.

The inaugural “Orange Book Patent Listing Dispute List” includes only a single patent listing dispute (concerning PRADAXA (dabigatran etexilate mesylate) and U.S. Patent No. 9,034,822); however, we expect the list to grow.