Regulatory News| July 27, 2022 | By
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The US Food and Drug Administration has released a final draft of guidance that addresses what to expect when sponsors receive complete response letters (CRLs) to their abbreviated new drug applications (ANDAs). The agency also finalized another guide that explains your responsibilities for maintaining and updating the orange bookwhich contains lists of information on patents and exclusivity of medicines with evaluations of therapeutic equivalence.
On July 22, the FDA published two final guidelines. The first entitled Failure to respond to a full response letter from ANDA within the statutory deadline sets out how much the agency is willing to work with sponsors who receive a CRL indicating that your application needs more information before the agency will consider approving it.
The FDA notes that it cannot keep incomplete ANDA applications open indefinitely, as the data provided in the application may become out of date and the science behind the drug may evolve. The agency typically gives sponsors one year to respond to a CRL with additional information to support ANDA approval. If sponsors can’t meet their obligations within that time frame, reviewers say they will close the application, meaning drug developers must start from scratch unless they can give the FDA a good reason for the delay.
“Under the Generic Drug User Fee Amendments Program, the FDA has seen a steady increase in pending ANDAs with industry for more than a year,” the guidance states. “Historically, the FDA, at its discretion, has generously granted requests for multiple extensions to respond to an individual CRL to the detriment of the ANDA evaluation process.”
“Long response times due to multiple extensions, which can result in applicants submitting an amendment addressing deficiencies years after ANDA’s initial evaluation and CRL issuance, are detrimental to the evaluation process and can create additional evaluation cycles,” he added. “Over time, the information presented in the original ANDA may become outdated due to changes such as new or revised United States Pharmacopeia requirements, reference drug labeling (RLD) changes, or other events, such as outdated evaluation of a facility. Also, over time, FDA review staff may have changed and it may take time for them to become familiar with the original ANDA.”
In the final guidance, the FDA sets out what sponsors can do to respond to a CRL, especially if they need more time to gather additional information to support their ANDA. Unlike the preliminary version of the guidance, the final version also includes an appendix of potential factors that FDA may deem reasonable to give sponsors additional time to complete their ANDA. (RELATED: Generic Drug Manufacturers Get Guidance on Tentative Approvals, CRLsNormative Approach September 28, 2020)
The second final guidance issued by the FDA entitled orange book questions and answers does exactly that. It is a question and answer session that describes the obligations that the agency has to update and maintain the orange book.
The FDA proposed revising the orange book in 2020 on a draft guidance and sought input from stakeholders on how parties used the book and what questions needed to be answered. (RELATED: The FDA seeks to review the Orange Book, seeks information on patent lists, Normative Approach May 29, 2020)
FDA takes note of the orange book is divided into four main parts: a prescription drug product list of marketed prescription drugs approved with therapeutic equivalence assessments, a list of OTC drugs that have been approved under new drug applications (NDAs) 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 for export only, or have never been marketed.
“The Orange Book contains additional information, including three appendices and two annexes related to patents and exclusivity,” the FDA noted. “The Orange Book website also has a number of additional resources that can help interested parties use the Orange Book and related questions.”
In addition, the agency says it also includes therapeutic equivalence evaluations for approved multi-source prescription pharmaceuticals.
“These evaluations were prepared to serve as public information and advice to state health agencies, prescribers, and pharmacists to promote public education on the selection of pharmaceutical products and encourage health care cost containment,” the FDA added. .
In the guide’s question-and-answer section, the 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, which drugs are not included in the book, and how sponsors may notify the agency of a change in the status of their medications to ensure that the information is up to date.
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