FDA finalizes ANDA CRL, Orange Book Q&A guidances

Regulatory NewsRegulatory News

| 27 July 2022 | by Ferdous Al-Faruque


The US Food and Drug Administration has published a final draft guidance that addresses what’s expected when sponsors get complete response letters (CRL) to their abbreviated new drug applications (ANDAs). The agency also finalized another guidance explaining its responsibilities for maintaining and updating the Orange Bookwhich contains lists of patent and exclusivity information for drugs with therapeutic equivalence evaluations.

On 22 July, FDA published two final guidances. The first titled Failure to Respond to an ANDA Complete Response Letter Within the Regulatory Timeframe lays out how much the agency is willing to work with sponsors who receive a CRL stating their application needs more information before the agency will consider approving it.

FDA notes that it can’t hold incomplete ANDA applications open indefinitely, as the data provided in the application may become outdated and the science the drug is based on may evolve. Typically, the agency gives sponsors a year to respond to a CRL with additional information to support approving the ANDA. If sponsors are unable to meet their obligations within that timeframe, reviewers say they will close the application which means drug developers have to start from scratch unless they can give FDA a good reason for the delay.

“Under the Generic Drug User Fee Amendments program, FDA has seen a steady increase of ANDAs pending with industry for more than a year,” the guidance states. “Historically, FDA, in its discretion, has liberally granted requests for multiple extensions to respond to an individual CRL to the detriment of the ANDA assessment process.”

“Lengthy times because of multiple extensions response, which can result in applicants submitting an amendment addressing deficiencies years after the initial assessment of the ANDA and obligation of the CRL, are disruptive to the assessment process and can create additional assessment cycles,” it added. “Over time, information submitted in the original ANDA can become obsolete because of changes such as new or revised United States Pharmacopeia requirements, labeling changes to the reference drug (RLD), or other events such as a facility evaluation becoming outdated. In addition, over time, FDA assessment staff may have changed, and it may take time for them to familiarize themselves with the original ANDA.”

In the final guidance FDA states what sponsors can do to respond to the CRL especially if they need more time to gather additional information to support their ANDA. Unlike the draft version of the guidance, the final version also includes an appendix of potential factors FDA may consider reasonable to give sponsors additional time to complete their ANDA. (RELATED: Generic drugmakers get guidance on tentative approvals, CRLsRegulatory Focus 28 September 2020)

The second final guidance published by FDA titled Orange Book Questions and Answers does exactly that. It is a Q&A outlining what obligations the agency has to update and maintain the Orange Book.

FDA proposed overhauling the Orange Book in 2020 in a draft guidance and sought stakeholder input on how parties used the book and what questions needed to be answered. (RELATED: FDA looks to overhaul Orange Book, seeks input on patent listings, Regulatory Focus 29 May 2020)

FDA notes the Orange Book is broken up into four main parts: a prescription drug product list of approved marketed prescription drugs with therapeutic equivalence evaluations, a list of over-the-counter drugs that have been approved under new drug applications (NDA) or ANDAs, a list of drugs approved under Section 505 of the Food, Drug and Cosmetic Act (FD&C Act), and finally, a list of drugs that have been discontinued, are intended only for export, or have never been marketed.

“The Orange Book contains additional information, including three appendices and two addenda related to patents and exclusivity,” FDA noted. “The Orange Book website also has a number of additional resources that can assist stakeholders with using the Orange Book and related questions.”

Additionally, the agency says it also includes therapeutic equivalence evaluations for approved multisource prescription drug products.

“These evaluations have been prepared to serve public information and advice to state health agencies, prescribers, and pharmacists to promote public education on drug product selection and to foster containment of health care costs,” FDA added.

In the Q&A section of the guidance FDA answers questions such as how often the agency plans to update the Orange Book with the latest list of drugs and their generic equivalents, what drugs are not included in the book and how sponsors can notify the agency about a change in status of their drugs to ensure the information is up to date.

© 2022 Regulatory Affairs Professionals Society.

Leave a Reply

%d bloggers like this: