The goals of GDUFA II, among others, are to “clarify regulatory expectations for prospective applicants early in product development, assist applicants to develop more complete submissions, promote a more efficient and effective ANDA review process, and reduce the number of review cycles to obtain ANDA approval” for complex products.

President Donald Trump signed the Food and Drug Administration Reauthorization Act (FDARA) into law on August 18, 2017. FDARA includes the reauthorization of the Generic Drug User Fee Amendments through September 2022 (GDUFA II). To follow the mandate, the Food and Drug Administration (FDA) has published a draft guidance for industry entitled “Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA” (the draft guidance). The FDA will accept comments on the draft guidance until December 4, 2017.

Why Now?

GDUFA II provisions went into effect October 1, 2017, and remain in effect through September 30, 2022. The goals of GDUFA II, among others, are to “clarify regulatory expectations for prospective applicants early in product development, assist applicants to develop more complete submissions, promote a more efficient and effective ANDA review process, and reduce the number of review cycles to obtain ANDA approval” for complex products. Accordingly, the draft guidance provides a mechanism for requesting meetings early in product development, before submission of ANDAs and during review of ANDAs. The purpose of the draft guidance is to assist ANDA applicants in preparing for and requesting meetings during the development and approval processes.

Complex Products Defined

Under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and as redefined in the GDUFA II Commitment Letter, complex products include:

  1. Products having complex active ingredients (such as peptides, polymers, complex mixtures, naturally sourced ingredients), complex formulations (such as liposomes and colloids), products requiring complex routes of delivery (such as for certain dermatological and ophthalmological products), or complex dosage forms (like transdermals, metered dose inhalers, extended-release injectables);
  2. Complex drug-device combination products; or
  3. Other products where complexity or uncertainty concerning the approval pathway or possible alternative approach would benefit from early scientific engagement.

Meeting Types

Under GDUFA II objectives, early scientific engagement between the FDA and ANDA applicants will help with the submission of high-quality, approvable ANDAs for complex products and expedite their approval. The FDA has named three types of meetings: meetings early in product development (product development meetings), meetings before submission of ANDA (pre-submission meetings), and meetings during review of ANDAs (mid-review-cycle meetings). As discussed below, the draft guidance includes discussion on the timing of the meetings, objectives of the meetings, the data packages required to request a meeting and the FDA’s methodology to grant or deny the meetings.

Product Development Meetings

The FDA anticipates more than one product development meeting for some ANDAs, but the FDA recommends submission of no more than one request for a product development meeting for a given complex product per year. The objective for the product development meetings is to advance product development early in the process by providing for discussion of specific scientific issues (e.g., a proposed study design, alternative approach or additional study expectations) and provide targeted advice regarding an ongoing ANDA development program. We believe that “early in product development,” under GDUFA II, may include a point where a prospective ANDA applicant has enough knowledge of the complex product but has no actual experimental data. In fact, such meetings will likely allow prospective ANDA applicants to take a more streamlined approach to product development.

Consistent with the GDUFA II Commitment Letter, the FDA will grant a product development meeting for complex products for which the FDA has not issued a product-specific guidance, or when a prospective ANDA applicant is proposing alternative equivalence evaluation (i.e., change in study type, such as in vitro to clinical). When these do not apply, the FDA may grant a product development meeting depending on available resources.

The FDA will grant a product development meeting only upon submission of a complete meeting package, including a data package and specific proposals for product development. A complete meeting package should be submitted electronically and include:

  • A pre-assigned ANDA number
  • Established product name
  • Chemical structure
  • Reference listed drug (RLD) and its application number
  • Proposed indication(s)
  • Dosage form, route of administration and dosing regimen (frequency and duration)
  • Meeting type being requested (i.e., product development meeting)
  • A brief statement indicating how the product meets the criteria for a complex product
  • A brief statement of the purpose and objectives of the meeting (including a brief background of the issues underlying the agenda)
  • A list of attendees with their titles and affiliations
  • Suggested dates and times
  • The proposed meeting format (i.e., written response, face-to-face or teleconference)
  • Background, such as a brief history and status of the development program
  • A list of questions grouped by discipline
  • A brief explanation of the context/purpose of the question with any supporting material
  • The draft guidance outlines provisions on how to reschedule, cancel and reapply for the product development meetings.

Pre-Submission Meetings

The FDA anticipates that the pre-submission meeting will take place approximately six months before submission of the ANDA. The objective for the pre-submission meetings is to provide an opportunity for prospective ANDA applicants to discuss the format and content of ANDA packages before filing, but not for the FDA to determine whether the application is acceptable for filing. As expected, the FDA will not perform a substantive review of the ANDA package for/during the pre-submission meeting; instead, the FDA will only identify items or information that should be clarified before submission of the ANDA.

A pre-submission meeting is available to prospective ANDA applicants whether or not a product development meeting has been requested/held but is not required for submission. The FDA will generally grant pre-submission meetings for prospective ANDA applicants that have had a product development meeting or received a written response. The FDA may grant a pre-submission meeting to a prospective ANDA applicant that did not have a product development meeting if, in the FDA’s judgment, the pre-submission meeting would improve review efficiency.

A complete meeting package should be submitted electronically. A complete meeting package for a pre-submission meeting is similar to the one discussed above for the product development meetings. The draft guidance outlines provisions on how to reschedule, cancel and reapply for the pre-submission meetings.

Mid-Review-Cycle Meetings

A mid-review-cycle meeting is only available to ANDA applicants that have participated in a prior product development or pre-submission meeting and will generally take place 30 days after the mid-point of the first review cycle. The objective for the pre-submission meetings appears to be to provide an opportunity for the FDA to discuss issues identified during review with the applicant.

ANDA applicants that participated in a product development and/or pre-submission meeting should not request a mid-review-cycle meeting. Instead, the regulatory project manager (RPM) assigned to the ANDA will contact the ANDA applicant to schedule a teleconference. The FDA intends to send the agenda to the applicant seven calendar days before the teleconference. During the mid-review-cycle meeting, the FDA will update the ANDA applicant regarding the status of the review, including possible deficiencies found.

GDUFA II Performance Goals

The FDA has committed to meet certain performance review goals. Based on these goals, the FDA will grant/deny 90 percent of requests within the following timeframe:

Meeting Type

2018-19

2020-22

Product development

30 days of receipt

14 days of receipt

Pre-submission

30 days of receipt

14 days of receipt

Mid-review cycle

N/A

N/A

The FDA will conduct meetings within 120 days of the date granted:

Meeting Type

2018

2019

2020

2021

2022

Product development

60%

70%

80%

90%

90%

Pre-submission

60%

70%

80%

90%

90%

Mid-review cycle

N/A

N/A

N/A

N/A

N/A

Conclusion

In summary, the FDA has initiated three types of meetings with ANDA applicants of complex products at various points in the product development cycle. An ANDA applicant may now schedule one or more product development meetings early in the product development cycle to discuss specific scientific issues and receive targeted advice from the FDA. When product development significantly progresses, about six months before filing of ANDA, an ANDA applicant may also schedule a pre-submission meeting to discuss the format and contents of ANDA package, without a substantive review. If an ANDA applicant has participated in a product development and/or pre-submission meeting, FDA will schedule a mid-review-cycle meeting with to discuss issues identified during review with the applicant. FDA hopes to achieve the submission of high-quality ANDAs for complex products and their speedy approval via this early scientific engagement consistent with the objectives of GDUFA II.

For Further Information

If you have any questions about this Alert, please contact Frederick (Rick) R. Ball, Carolyn A. Alenci, any of the attorneys in our Pharmaceutical, Medical Device, Pharmacy and Food industry group or the attorney in the firm with whom you are regularly in contact.

Disclaimer: This Alert has been prepared and published for informational purposes only and is not offered, nor should be construed, as legal advice. For more information, please see the firm's full disclaimer.