Controlled correspondence: FDA offers advice for generic sponsors

US Food and Drug Administration (FDA) officials discussed when it is best for applicants to submit a controlled correspondence or request a pre-ANDA meeting for questions related to their generic drug applications at a Thursday meeting sponsored by the CDER Small Business and Industry Assistance (SBIA). They also addressed the best ways of framing questions during a controlled correspondence to ensure they are answered the first time around.

Robert Lionberger, director of the Office of Research and Standards (ORS) in the Office of Generic Drugs (OGD), said the agency wants to help sponsors understand the controlled correspondence process “to help you ask questions so that you get the answers you need the first time” and to avoid multiple review cycles. In FY 2024, the agency processed 2,792 controlled correspondences.

He mentioned that this was OGD’s inaugural meeting under the new administration and that much work was done “behind the scenes” to ensure the event took place.

Controlled correspondences are written inquiries to the FDA regarding specific elements of a sponsor's generic drug development program or are questions related to post-approval submission requirements. In March 2024, the FDA issued a final guidance outlining the process for generic drug manufacturers to submit controlled correspondence.

Notably, some changes compared to the GDUFA II program include the introduction of Level 1 and Level 2 categories for controlled correspondence requests.

Yan Wang, the deputy director of the Division of Therapeutic Performance (DTP in ORS), said that controlled correspondence can be used to obtain feedback on the acceptability of an analytical method testing formulations, to seek clarification on the design of a bioequivalence study, to discuss potential deviations or alternative approaches that do not adhere to the agency’s recommendations in product-specific guidances (PSGs) or ask about the agency’s interpretation of a guidance, or to discuss a proposed quality control strategy for a stability testing plan.

She stated that upon receipt, OGD triages these requests to the relevant discipline within the office or to outside offices, such as the Office of Pharmaceutical Quality depending on the expertise needed.

To ensure the agency addresses the questions at the outset, Wang said that sponsors should provide comprehensive background information and supporting data before presenting their inquiries. It’s important to consider asking questions that highlight specific technical issues, such as a study protocol or an alternative bioequivalence (BE) study design. Additionally, sponsors should focus on questions that seek feedback on a proposed strategy, rather than using open-ended questions.

There are several common reasons why correspondence may not be answered promptly, necessitating the FDA to go back to the sponsor for more information.

One reason could be that the sponsor did not provide enough background information or supporting data to effectively address the question. Another possibility is that the question is poorly phrased. Additionally, questions that are too general might not be directly addressed at the pre-ANDA stage. Another issue is sending mixed questions to multiple review divisions.

Lionberger also addressed the situations and key differences between requesting a pre-ANDA meeting and submitting controlled correspondence.

He indicated that submitting controlled correspondence is preferable for very specific questions. In contrast, pre-ANDA meetings are designed for more complex issues that involve multiple divisions or groups.

Controlled correspondence: FDA offers advice for generic sponsors

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