As the Biden administration and the US Congress continue to debate ways to address perceived concerns about prescription drug prices, the Food and Drug Administration (FDA) is taking action. Under its Drug Competition Action Plan (DCAP), administered by the Office of Generic Drugs (OGD), the FDA has issued approximately 24 guidance documents since 2017, directing industry stakeholders on how to develop, prepare and submit abbreviated new drug applications (ANDAs), so that generic drugs can gain timely FDA approval and reach the market faster. In January 2022, the FDA released three more guidance documents in the DCAP series.
By helping to make additional low-cost generic drugs available, the FDA believes this can impact the overall drug price burden. For example, according to the latest Congressional Budget Office (CBO) Reportt, the average net price of a prescription drug in the Medicare Part D and Medicaid programs fell from 2009 to 2018, and this drop “reflects increased use of cheaper generic drugs.” In the words of the FDADCAP “helps break down barriers to generic drug development and market entry with the goal of driving competition so consumers can get the drugs they need at affordable prices.”
When we asked the OGD about the importance of the last three guidelines, Maryll Toufanian, Director of the Office of Generic Drug Policy, replied:
As stated in the DCAP, the FDA understands that it is essential to provide as much transparency as possible in our regulatory expectations. This allows for maximum efficiency for claimants submitting generic drug claims and for our assessment of those claims. Guidance like the one recently released is a key tool in our toolbox to achieve this.
Below is a list of recently released DCAP guidance documents and a brief description of each. Although much of the information has already been provided to industry stakeholders in various forms, it is important for every company considering submitting an ANDA (or has an ANDA pending) to carefully review these published versions of the guidance from the FDA and update their regulatory procedures. Therefore.
REQUESTS FOR INFORMATION AND DISCIPLINE REVIEW LETTERS UNDER GDUFA, GUIDANCE FOR INDUSTRY
Updating a 2017 draft, these final guidelines detail how the DMO will provide ANDA applicants with “preliminary thoughts on possible gaps” after the DMO’s initial assessment for ANDAs submitted between 2018 and 2022 in the under the 2017 Generic Drug User Fee Amendments (GDUFA II). Although future “GDUFA III” legislation will likely change some details, this guidance is also instructive for planning purposes for ANDAs to be filed in 2023 and beyond.
The guidelines explain that midway through the FDA’s evaluation of an ANDA’s first evaluation cycle (the mid-cycle date), the DMO will issue a Discipline Review Letter (DRL) to ANDA’s applicant to share their preliminary thoughts on a possible application. deficiencies. Alternatively, a Request for Information (RI) can be sent to request additional information or clarification needed to conduct a discipline assessment (eg bioequivalence, labeling or quality). However, these letters will not be sent when the discipline considers that it can act on the ANDA with the information contained in the request.
The use of these letters is intended to provide applicants with the FDA’s thoughts as soon as possible so that they can modify the ANDAs and continue the evaluation process. The FDA hopes that this mid-cycle communication will minimize the number of review cycles needed for approval. Candidates’ responses will not be categorized as a major or minor change to the ANDA and, therefore, will not delay the assessment clock (formerly, the “Exam Clock”), unless the response does not contain information not requested by the FDA or information that requires further evaluation. The letters do not guarantee that a Complete Response Letter (CRL) will not be issued, as the letters reflect feedback from the assessment team, but not feedback from all levels of supervision within other departments.
ANDA SUBMISSION GOOD PRACTICES, INDUSTRY TIPS
In this guide, the OGD highlights common ANDA shortcomings and provides detailed recommendations, so that ANDA applicants can file compliant submissions under GDUFA II and avoid CRLs, data cycles multiple reviews and long approval times. The information is an update of an OGD guide published in 2018 and details the OGD program improvements developed under GDUFA II. By outlining common errors, OGD intends to foster the development of high quality submissions and promote the prompt correction of ANDA deficiencies.
The guidelines cover almost all types of information required in an ANDA, such as patent certifications and exclusivity requirements, labeling, drug substance and drug product descriptions, impurities and intermediates, product quality and manufacturing processes, as well as bioequivalence and dissolution data. Other departments have specific submission and formatting requirements for each eCTD module in all of these areas, so the gap descriptions are helpful and may answer questions that have plagued regulatory affairs staff.
The guide also provides useful information for keeping ANDAs pending, since the initial filing of an ANDA is only the first step to obtaining ANDA approval. During the evaluation cycle, applicants must continually update the information in the ANDA related to many topics, including Paragraph IV patent litigation, Orange Book changes, manufacturing changes , batch validation and stability data, risk assessment and mitigation strategy implementation, and commercial launch plans. Avoiding submission gaps when submitting updates to a pending ANDA is just as critical as the initial ANDA submission.
ANDA LABELING REVISION FOLLOWING RLD LABELING REVISION, INDUSTRY GUIDANCE PROJECT
This draft guidance updates information that the DMO had previously published in April 2000 via a guidance of the same name. Twenty-two years later, FDA reminds ANDA holders of their continued obligation to ensure product labeling is accurate, not false or misleading, and “the same” as the corresponding reference medicinal product labeling (RLD). For these reasons, once the FDA approves relevant RLD labeling changes, an ANDA holder should update their labeling “as soon as possible.” To learn about RLD labeling changes, ANDA applicants and ANDA holders should proactively monitor public information, such as the [email protected] web page and the CDER New ListServ.
The DMO also explains that ANDA labeling changes must be organized according to eCTD modules and submitted in electronic format through the electronic submission gateway. An annotated side-by-side comparison of the proposed ANDA labeling and the approved RLD labeling continues to be required.