The US Food and Drug Administration (FDA) is out with its fourth draft guidance document under the 2012 Generic Drug User Fee Act, this time explaining the nuances of how generic drug companies can submit requests for information from the agency.

Background

GDUFA was passed in 2012 as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), and is modeled off other FDA user fee programs such as the Prescription Drug User Fee Act (PDUFA) and the Medical Device User Fee Act (MDUFA). In general, the program is meant to provide FDA with additional funding to conduct reviews and strengthen its regulatory infrastructure. In return, the agency is expected to provide generic drug companies with predictable timelines for approval decisions and more advice for how to navigate the regulatory process.

As part of the GDUFA negotiating process, FDA and industry also signed onto a GDUFA "commitment letter," which called for the agency to publish guidance documents on several important topics. Already, FDA has published three of those guidance documents:

• ANDA Submissions—Content and Format of ANDAs
• ANDA Submissions—Amendments and Easily Correctable Deficiencies Under GDUFA
• ANDA Submissions—Prior Approval Supplements Under GDUFA

And in a Federal Register announcement in August 2014, FDA indicated that it would be coming out with two additional guidance documents in the coming weeks:

• ANDA Submissions—Refuse to Receive for Lack of Proper Justification of Impurity Limits
• Controlled Correspondence Related to Generic Drug Development

New Guidance

FDA has now published the latter of those two GDUFA guidance documents, Controlled Correspondence Related to Generic Drug Development.

The guidance, published 26 August 2014, is meant to provide information "regarding the process by which generic drug manufacturers and related industry can submit correspondence to FDA requesting information related to generic drug development," FDA explains in the guidance. The document also describes how the communications process works.

That’s because in addition to timelines for approval decisions, GDUFA also contained timelines for FDA to respond to so-called "controlled correspondence"—essentially formal questions posed to FDA prior to the review process and intended to clarify questions capable of affecting the review of a product.

FDA defines the term as: "A correspondence submitted to the Agency, by or on behalf of a generic drug manufacturer or related industry, requesting information on a specific element of generic drug product development."

Coming GDUFA Requirements

As outlined in the GDUFA commitment letter, FDA action on controlled correspondence letters is set to begin next year and steadily ramp up in intensity.

• FDA will respond to 70 percent of controlled correspondence in 4 months from date of submission in fiscal year (FY) 2015.
• FDA will respond to 70 percent of controlled correspondence in 2 months from date of submission in FY 2016.
• FDA will respond to 90 percent of controlled correspondence in 2 months from date of submission in FY 2017.
• If the controlled correspondence requires input from the clinical division, one additional month will be added to the goals outlined above.

Potential Delays

The guidance notes several ways in which controlled correspondence letter responses might be delayed. For example, if FDA receives a citizen petition regarding the same subject, it will not respond to the letter until the petition has received a response. Citizen Petitions will not be considered controlled correspondence, FDA said. Similar treatments will be given to petitions for reconsideration and requests for stays, FDA explained.

Similarly, if FDA is considering a matter separately from the letter, it might also delay its response to a controlled correspondence letter.

FDA will also continue to treat as separate three types of controlled correspondence, which have historically been (and will continue to be) subject to their own controls:

• requests for recommendations on the appropriate design of bioequivalence  (BE) studies for a specific drug product (BE guidance requests)
• requests for review of BE clinical protocols (clinical protocol requests)
• requests for meetings to discuss generic drug development prior to ANDA submission (pre-ANDA meeting requests)

Content

The guidance goes on to note that controlled correspondence should be submitted electronically, and should not be addressed to an individual FDA employee.

The exact format of a controlled correspondence letter can also be found in the guidance.

Controlled Correspondence Related to Generic Drug Development (FR)