Competitive Generic Therapies: FDA Issues Final Guidance

The FDA Reauthorization Act of 2017 (FDARA) created a new pathway to incentivize the development of generic drugs where there is inadequate competition.  Under this new pathway [new Section 506H of the Federal Food, Drug, and Cosmetic Act (FDC Act)], FDA may, at the request of an applicant, designate a drug with “inadequate generic competition” as a Competitive Generic Therapy (CGT).  At the request of an applicant, FDA may also expedite the development and review of an abbreviated new drug application (ANDA) for a drug designated as a CGT.

In addition, FDARA created a new type of 180-day market exclusivity for the first approved applicant of a drug with a CGT designation for which there were no unexpired patents or exclusivities listed in “the Orange Book” at the time of original submission of the ANDA. ¹   This new 180-day exclusivity (CGT exclusivity) is intended to incentivize competition for drugs that are not protected by patents or exclusivities and for which there is inadequate generic competition. ²

In March of this year, the Food and Drug Administration issued final guidance on CGT.  The guidance describes:  (1) the process applicants should follow to request CGT designation, and the criteria FDA will use to designate a drug as a CGT, (2) the actions FDA may take to expedite the development and review of ANDAs for drugs designated as CGTs, and (3) how FDA will implement the new provision for 180-day CGT exclusivity.

We will summarize the key points from the guidance in this Bulletin.

Highlights

• FDA may designate a drug as a CGT after determining that there is inadequate generic competition for that drug. The term inadequate generic competition is defined in Section 506H of the FDC Act to mean that there is not more than one approved drug included in the active section of the Orange Book. ³   This may be either:  (1) the reference listed drug (RLD) (e.g., the drug to which a generic drug must demonstrate bioequivalence), or (2) an approved generic drug with the same RLD as the drug seeking CGT designation.

• FDA interprets Section 506H of the FDC Act to describe a process that results in a designation specific to a particular application and drug product. FDA does not interpret CGT designation to automatically apply to all applicants for such drug.  Thus, CGT designation should be requested for each  Once FDA designates a product as a CGT, it will remain designated as a CGT, even if there is no longer inadequate competition for that drug prior to approval of the application.

• Applicants may submit CGT designation requests concurrently with, or at any time prior to, the original ANDA submission. FDA will not consider a Request for Designation if it is submitted after the submission of the original ANDA, unless a refuse-to-receive determination has been made for the application.

• Requests for CGT designation should include a pre-assigned ANDA number, a statement supporting the Request for Designation (identification of the particular drug product that will serve as the basis of submission for the applicant’s proposed application), and information supporting the applicant’s assertion that there is inadequate generic competition, as defined in the FDC Act. FDA intends to make determinations on Requests for Designation within 60 calendar days of receipt of the applicant’s request.

• Applicants for drugs that FDA has designated as CGTs may request expedited development and review of their ANDAs.
  • Considerations for Expedited Development – FDA will consider the following factors in deciding whether to grant requests for expedited development:
    • the complexity of developing an application for the specific drug subject to the request
    • the potential public health impact of the product (e.g., severity of the condition treated, size of affected patient population, availability of therapeutic alternatives)
    • the impact on FDA resources and other existing workload commitments
  • Actions FDA May Take to Expedite Development – In order to expedite development of a CGT, FDA may grant Product Development Meetings to discuss specific scientific and/or regulatory issues or questions, or Pre-Submission Meetings to discuss and explain the content and format of an ANDA to be submitted.
  • Considerations for Expedited Review – FDA generally intends to expedite the review of ANDAs for drugs designated as CGTs when the applicant has participated in the pre-ANDA meeting program prior to the submission of the ANDA. FDA does not intend to expedite the review of ANDAs covering CGTs if, at the time of ANDA submission, unexpired patents or exclusivities were listed in the Orange Book for the RLD.  FDA will try to act on the ANDA prior to the Generic Drug User Fee Amendments (GDUFA) goal date; however, a CGT designation does not guarantee a shorter GDUFA goal date.
  • Actions FDA May Take to Expedite Review – FDA may: (1) offer a mid-review-cycle meeting during the first review cycle, and (2) involve experienced review and project management staff in a collaborative, cross-disciplinary review, including the involvement of senior management.

• FDARA amended the FDC Act to create a new type of 180-day CGT marketing exclusivity for the first approved applicant that:
  • obtains approval of an ANDA for a drug that has been designated as a CGT and for which there were no unexpired patents or exclusivities listed in the Orange Book for the relevant RLD at the time the applicant submitted the original ANDA; and
  • commercially markets such drug within 75 calendar days after the approval of the ANDA.

• There can be multiple first approval applicants for the same CGT, if all such ANDA applicants obtain approval for the same CGT on the same day, and such approvals constitute the first ANDA approvals for this CGT.

• An ANDA applicant may still qualify as a first approved applicant even if another ANDA referencing the same RLD, but without a CGT designation, is approved prior to the approval of the first approved applicant’s ANDA. FDA does not consider the prior ANDA approval to constitute the first approval of an ANDA for a CGT.

• The 180-day CGT exclusivity period is triggered by the first commercial marketing of the competitive generic therapy (including the marketing of an authorized generic) by any first approved applicant. FDA is not restricted from approving other ANDAs that are the same as the CGT prior to or after the approval of a first approved applicant’s ANDA for the CGT unless and until the first approved applicant has commenced commercial marketing.

• FDA intends to permit a first approved applicant to relinquish and/or grant selective waiver of CGT exclusivity, similar to the aforementioned 180-day first-to-file patent challenge exclusivity.

• FDARA also included a provision under which a first approved applicant could forfeit eligibility for CGT exclusivity. FDA interprets this language to mean that the first approved applicant will forfeit CGT exclusivity if the applicant fails to market within 75 days, beginning on the calendar day after the date on which approval of the first approved applicant’s application for the CGT is made effective, and not the date of approval itself.  To ensure that FDA receives timely notification of first commercial marketing, the first approved applicant should submit correspondence to the ANDA informing the agency that it has commenced marketing, with a duplicate copy submitted to the Office of Generic Drug’s Patent and Exclusivity Team at CDER-OGDPET@fda.hhs.gov.

AGG Observations

• Applicants that are developing generic drugs which meet the criteria for CGT designation should consider submitting a request to FDA concurrently with, or any time prior to, ANDA submission.

• Despite the potential benefits of CGT designation, it is important that generic drug applicants keep two important things in mind:
  • Drugs may be designated as CGTs, but may not be eligible for CGT exclusivity (e.g., commercial marketing of the drug does not commence within 75 days after approval).
  • If FDA grants CGT designation, applicants must still request expedited development and/or review, and FDA is not required to take any actions. As explained above, the guidance provides considerations for expedited development and review, and actions FDA may take to expedite development and review, but FDA is not required to take any action.  This is rooted in the statutory language of Section 506H of the FDC Act, which provides that the Secretary may, at the request of an applicant, expedite the development and review of an ANDA for a drug designated as a CGT.

• CGTs can be a benefit to an ANDA company in one case, but it can also be a potential commercial obstacle in another. For example, a company may qualify for designation and exclusivity for one product.  However, it could find itself on the short end of the stick if a competitor obtains CGT exclusivity.  Therefore, generic companies must know the rules of the CGT game as they work on their commercial development plans.

[1] FDA’s Office of Generic Drugs publishes a list on the FDA website of all approved ANDAs for drug products that received CGT designation, and indicates which ANDAs were also eligible for CGT exclusivity.  The list is updated every two weeks.  The Orange Book also posts a CGT code in the “Exclusivity Data”section.

[2] This exclusivity is different from another type of 180-day market exclusivity given for the first (ANDA) applicant who submits a certain patent certification, not discussed here.

[3] 21 U.S.C. § 356H.