Drug and Device September 2023 - EAS Consulting Group

Reminder that FY2024 GDUFA payments are due 2 October 2023. The FDA does allow a 20 calendar day grace period, after which arrears lists will be published with the names of companies that have failed to make payment. Failure to pay required user fees by this deadline deems any generic drugs marketed by a company on the arrears list as misbranded.

The drug establishment registration renewal and drug listing certification period begins 1 October 2023. The FDA will be updating two fields this year which will require a change to many current listings marketed as OTC monograph drugs. Aligning with changes to the OTC monograph system brought by the CARES Act, the marketing category field and the application number field options will be changed. The FDA has made ‘deemed final orders’ available on their OTC MONOGRAPHS @ FDA webpage resource. For example, in previous submissions, the marketing category for a stimulant drug product for over-the-counter human use was reported “OTC monograph final” / “part340” in a listing. Henceforth, the marketing category will be reported by “OTC monograph drug” / “M011”. The application field will also have the option to enter ‘505G(a)(3)’ to identify a drug product that was categorized in category III for safety or effectiveness in the preamble of a tentative final monograph that is the most recently applicable proposal or determination for such drug issued under 21 CFR part 330, and that was not deemed to be a new drug under section 505G(a)(4), until such time that a final order is issued for such.

Per the FDA’s Electronic Submission Template for Medical Device 510(k) Submissions final guidance document, starting 1 October 2023, all 510(k) submissions, unless exempted, must be submitted as electronic submissions using eSTAR through the CDRH Portal. eSTAR is the only available electronic submission template to facilitate the preparation of 510(k) electronic submissions.

On Friday 15 September 2023, the FDA issued a draft guidance shedding light on the much-anticipated MoCRA registration and listing requirements. The guidance, titled “Registration and Listing of Cosmetic Product Facilities and Products” gives an overview of the process. In addition to the guidance document, the FDA also published an 81 slide draft of screen shots of COSMETICS DIRECT, the program which will be used to electronically submit information to the agency. Paper submissions (Form 5066 Registration of Product Facility and Form 5067 Cosmetic Product Listing) are allowed, but industry is highly encouraged to submit registration and listing information electronically via the Cosmetics Direct portal. For anyone familiar with CDER Direct (drug submissions to the FDA), the new cosmetic portal will look very similar. The fields are different as they are tailored to cosmetic submissions, but the program appears as though it will function the same way.

Highlighted DRAFT Guidances Available for Comment

DRAFT Guidance: Post-Warning Letter Meetings Under GDUFA

This guidance provides information on the implementation of the Post-Warning Letter Meeting process for certain facilities, a program enhancement agreed upon by the Agency and industry as part of the negotiations relating to the reauthorization of GDUFA. A Post-Warning Letter Meeting, is a meeting with FDA regarding the facility’s remediation of deficiencies identified in a warning letter. This guidance specifically describes the process in the GDUFA III commitment letter for how an eligible facility may request a Post-Warning Letter Meeting with FDA regarding the facility’s ongoing remediation efforts to current good manufacturing practice deficiencies described in a warning letter, how to prepare and submit a complete meeting request package, and how FDA intends to conduct the Post-Warning Letter Meeting. Comments may be submitted by 6 November 2023.

DRAFT Guidance: Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications

The purpose of this guidance is to provide information to applicants on how FDA intends to use alternative tools to assess manufacturing facilities identified in a marketing application (i.e., NDA, ANDA, BLA, or a supplement to any of these types of applications). As part of the negotiations relating to the reauthorization of PDUFA and BsUFA, FDA agreed to issue guidance on the use of alternative tools to assess manufacturing facilities named in pending applications and to incorporate best practices from the use of such tools during the Coronavirus Disease 2019 (COVID-19) pandemic. Comments may be submitted by 21 November 2023.

EAS is monitoring the agency’s further actions after FDA issued Warning Letters to firms marketing unapproved eye products. The agency stated that the investigation of eye products is ongoing, and they may take additional regulatory or enforcement actions.

Highlighted Guidance Documents

Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process”

FDA has developed this guidance document to assist industry in preparing PMAs, HDEs, IDEs, 510(k)s, and De Novo requests for medical devices that come into direct contact or indirect contact with the human body in order to determine the potential for an unacceptable adverse biological response resulting from contact of the component materials of the device with the body. The purpose of this guidance is to provide further clarification and updated information on the use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” to support applications to FDA.

Annual Status Report Information and Other Submissions for Postmarketing Requirements and Commitments: Using Forms FDA 3988 and FDA 3989 Guidance for Industry

This guidance covers the purpose of each form, when to use these forms, and how to submit these forms. The guidance also explains where applicants will be able to find the forms and instructions. This guidance finalizes the draft guidance of the same name issued on October 21, 2020.

Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies

This guidance recommends approaches that sponsors of clinical trials of medical products can consider when there is a major disruption to clinical trial conduct and operations due to disasters or public health emergencies, which can include but are not limited to hurricanes, earthquakes, military conflicts, infectious disease outbreaks, or bioterrorist attacks. The appendix to this guidance further explains those approaches by providing answers to questions that the Agency has received about conducting clinical trials during major disruptions.

DSCSA Standards for the Interoperable Exchange of Information for Tracing of Certain Human, Finished, Prescription Drugs Guidance for Industry

This guidance identifies the standards necessary to facilitate adoption of secure, interoperable, electronic data exchange among the pharmaceutical distribution supply chain, and clarifies the trading partners, products, and transactions subject to such standards. This guidance finalizes the revised draft guidance of the same title, issued in July 2022.

DRAFT Guidances Available for Comment

DRAFT Guidance: Best Practices for Selecting a Predicate Device to Support a Premarket Notification [510(k)] Submission

FDA is issuing this draft guidance to provide our current thinking on the use of best practices in selecting a predicate device in 510(k) submissions to enhance the predictability, consistency, and transparency of the 510(k) Program. FDA developed this draft guidance in response to public feedback, and to continue to modernize the framework for 510(k) review. The recommendations in this draft guidance propose factors for consideration as best practices for choosing a predicate device that focus on characteristics of the predicate, including selecting a predicate device that was cleared using well-established methods, meets or exceeds expected safety and performance, is without unmitigated use-related or design-related safety issues, and is without an associated design-related recall. Comments may be submitted by 6 December 2023.

DRAFT Guidance: Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions

FDA is issuing this draft guidance to provide our current thinking on the use of clinical data in 510(k) submissions to enhance the predictability, consistency, and transparency of the 510(k) Program. FDA developed this draft guidance in response to public feedback, and to continue to modernize the framework for 510(k) review. The recommendations in this draft guidance provide additional clarity and context for situations when clinical data may be necessary to demonstrate substantial equivalence. The recommendations are intended to advance safety and innovation as well as promote consistency and facilitate efficient review of 510(k) submissions that include clinical data. Comments may be submitted by 6 December 2023.

DRAFT Guidance: Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence

The Food and Drug Administration is announcing the availability of a draft guidance for industry entitled “Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence.” Although FDA’s evidentiary standard has not changed since 1998, there is a need for more Agency guidance to describe how one adequate and well-controlled clinical investigation and confirmatory evidence can be used to meet the substantial evidence requirement. Comments may be submitted by 18 December 2023.

DRAFT Guidance: Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products

This guidance provides recommendations to industry on formal meetings between the Food and Drug Administration and sponsors or applicants relating to the development and review of drug or biological drug products regulated by CDER and CBER. This guidance does not apply to abbreviated new drug applications, applications for biosimilar biological products, or submissions for medical devices. For the purposes of this guidance, formal meeting includes any meeting that is requested by a sponsor or applicant following the procedures provided in this guidance and includes meetings conducted in any format. Comments may be submitted by 21 December 2023.

All Guidance Documents can be searched on the FDA’s website.