On February 6, 2015, FDA published in the Federal Register a Proposed Rule (PR) entitled: “Abbreviated New Drug Applications and 505(b)(2) Applications”. FDA said that the PR is intended to implement certain portions of the Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA), which amended portions of the Federal Food, Drug and Cosmetic Act (FD&C Act) related to abbreviated new drug applications (ANDAs) and new drug applications (NDAs) submitted under Section 505(b)(2) of the FD&C Act (505(b)(2) NDAs).

FDA’s PR is massive – even in Federal Register type it is nearly 100 pages. Here is a synopsis of some of the major provisions, many of which have been implemented by FDA since the MMA but not codified, others new (marked “new” with the proviso that many of these provisions may seem new but have been followed by the Office of Generic Drugs (OGD)):

  • Includes a long list of new, revised, or relocated definitions related to ANDAs and 505(b)(2) NDAs, such as “first applicant”, “substantially complete application”, and “tentative approval”.
  • Revises and streamlines submission of patent information on patents that claim the drug substance or drug product, claim only a polymorph, and certain NDA supplements.
  • Reissued patents will be considered in the “single bundle” of the original and reissued patent rights, making the timing of submission of patent information to the original patent critical; also there is the potential in a narrowing reissue that the original patent will be delisted.
  • Revises language clarifying the type of information an NDA holder needs to provide to list a method of use patent, limiting the use code to the portion of the labeling or indication relevant to the method of use claimed by the patent to prevent overbroad use codes (new).
  • Further describes FDA’s practice to not require (but still permit) pending ANDAs or 505(b)(2) NDAs to certify to untimely listed patents (i.e., listed more than 30 days after patent issuance).
  • Expands FDA’s category of untimely filed patents to include descriptions of the approved methods of use if such changes do not relate to corresponded changes in the labeling or are not submitted within 30 days after such labeling changes (new).
  • Defines the patent submission date of information submitted by an NDA holder to be the earlier of the date on which a Form FDA 3542 is date-stamped by OGD’s Document Room or officially received electronically by FDA (new).
  • Enhances FDA’s response to patent listing challenges by if in response to challenge: (1) the NDA holder confirms the accuracy of the information (of the improper listing or requested modification of the use code), (2) fails to timely respond, or (3) submits a revision to the use code that does not provide adequate clarity to FDA to determine whether the scope of a proposed labeling carve out would be appropriate based on the NDA holder’s use code and the approved labeling, FDA will then review proposed labeling carve-outs for an ANDA or 505(b)(2) NDA with deference to the ANDA or 505(b)(2) NDA applicant’s interpretation of the scope of the patent (new).
  • Expressly requires a correction or change in the patent information by the NDA holder if: (1) the patent or patent claim no longer meets the statutory requirement for listing, (2) the NDA holder is required by court order to amend the patent information or withdraw the patent from the list, or (3) the term of the listed patent is extended under patent term extension provisions.
  • Expressly describes when an ANDA or 505(b)(2) NDA applicants must provide its Paragraph IV notice (patent challenge – invalidity, unenforceability, or non-infringement) – in terms by when such notice may not be provided and when it must be provided:
  • Such notice may not be provided until FDA sends an “acknowledgement letter” or “paragraph IV acknowledgement letter” that the application is sufficiently complete to permit a substantive review, even if the patent certification is amended before the ANDA is deemed filed (new).
  • For newly listed patents, such notice may not be provided until the first working day after the patent is published in the Orange Book (new).
  • ANDA applicants failing to send their paragraph IV notice within 20 days after the postmark will be deemed delayed by the number of days by which the time frame was exceeded, which may result in a loss of the 180-day exclusivity (new).
  • Proposes expanding acceptable methods for sending notice of paragraph IV certifications to include “designated mail services” (new).
  • Expressly provides that a patent withdrawn by the NDA holder and requests removal following a court decision will be done so only after FDA determines that no first applicant is eligible for 180-day exclusivity or such exclusivity is extinguished and exempting 505(b)(2) applicants from providing or maintaining a certification to withdrawn patents.
  • Expressly provides that notice to a reissued patent following certification to its original patent follows FDA’s bundling of rights theory that the subsequent notice does not determine the eligibility for 180-day exclusivity or establish a separate right to such exclusivity (new).
  • Expressly requires ANDA and 505(b)(2) NDA applicants to submit a new patent certification that claims the listed drug or an approved method of use to accompany an amendment or supplement to add a new indication or other condition of use, or to add a new strength, or change an existing strength.
  • Expressly requires ANDA and 505(b)(2) NDA applicants to provide a new patent certification for an amendment to make “other-than-minor changes in product formulation or to change the physical form or crystalline structure of the active ingredient” (new)
  • Expressly prohibits a submission as an amendment or supplement that seeks approval: (1) in a 505(b)(2) NDA of “[A] drug that is different that the drug” than the drug identified in the original 505(b)(2) or (2) in an ANDA “a drug referring to a different listed drug” than the drug cited in the ANDA submission (new).
  • Expressly requires 505(b)(2) NDA applicant to identify a pharmaceutically equivalent product, if already approved, as a listed drug to rely upon rather than using the 505(b)(2) pathway to circumvent certification requirements that would have applied if the product were eligible for filing as an ANDA (not new but inconsistently applied).
  • Describes in a more comprehensive manner the timing for approval of an ANDA or 505(b)(2) based on patent certifications submitted and exclusivity provisions that apply, as well as link this description to the limitations on multiple 30-month stays for certain patents submitted on or after August 18, 2003 (new).
  • Clarifies that the statutory 30-month stay begins at the later date of receipt of the paragraph IV certification by any owner of a listed patent or by the NDA holder.
  • Codifies the MMA’s amendments regarding the type of Federal district and appellate court decisions in patent litigation that will terminate the 30-month stay and lead to approval of an ANDA or 505(b)(2) NDA, as well as included some new scenarios such as when a stay may be terminated, including written consent to approval by the patent owner or exclusive licensee, a court terminating the stay, or a court order of dismissal without a finding of infringement (scenarios new).
  • Modifies the types of events that can trigger the start of the 180-day exclusivity period, in particular requiring a first applicant to submit correspondence to its ANDA notifying FDA within 30 days of the date of commercial marketing of the drug product; if such notice is not provided, FDA will deem the date of first commercial marketing to be the date of the drug product’s approval (notice and penalty new).
  • Expands the scope of documentation that an applicant must submit to FDA regarding patent-related court actions and document agreements to make sure FDA is properly advised of information that may affect the timing of approval of an ANDA or 505(b)(2) NDA.

Comments may be submitted on the PR by May 7, 2015 and for comments related to information collection under the Paperwork Reduction Act of 1995 by March 9, 2015, both under Docket No. FDA-2011-N-0830. While many of the items in the proposed rule incorporate either the MMA or previous FDA rulemaking that had not been previously codified, there is a lot to digest and consider for possible comment and possibly consider “new”.