Bryan J. Coleman, Senior Director, Pharmaceuticals and Medical Devices.
FDA’s Refuse to Accept Policy for 510(k)s released January 30, 2018 laid out specific procedures the agency must follow when reviewing 510(k) submissions to assess whether the application meets a minimum threshold of acceptability so that it can move forward to a substantive review. FDA has been working towards a timely review process and this initial acceptance review enables the agency to determine whether specific required items are contained in the application and whether a 510(k) application is appropriate for the type of device under review. The agency’s ability to designate quickly those applications worthy of a substantive review should facilitate a better concentration of resources as the agency will only review those submissions determined to be complete.
An acceptance review is only looking only at whether submissions are administratively complete prior to a substantive review. During the substantive review, the reviewers will make a determination regarding substantial equivalence under section 513(i) of the FD&C Act, 21 U.S.C. § 360c(i). To find a device substantially equivalent under section 513(i) of the FD&C Act, FDA must find that it has the same intended use as the predicate device, and either has the same technological characteristics as the predicate device, or has different technological characteristics, as defined at section 513(i)(1)(B), and the submission contains information, including appropriate clinical or scientific data if necessary, that demonstrates the device is as safe and effective as the predicate and does not raise different questions of safety and effectiveness than the predicate.
FDA will assess proposed labels, labeling, and instructions as required by 21 CFR 807.87(e) as well as a description of the materials, design, and other features of the device to determine whether the product has the same technological characteristics as those of the predicate and whether any differences raise different questions of safety and effectiveness under section 513(i) of the FD&C Act.
The acceptance review does not take into account whether the documentation submitted contains accurate or adequate information, only that all of the required information is there. This initial acceptance review will be completed within 15 days, per the agency’s self-imposed requirement, and in the case of a delay, the primary contact named in the application will receive a letter, sent on the 16th day, stating an RTA has not yet been conducted.
FDA’s newly designed checklists are helpful for organizing supporting information and ensuring complete data is submitted. Submitters are encouraged to include those checklists as part of their submission application to facilitate FDA’s review and may wish to indicate where specific items mentioned in the checklist are found. Should a particular element not be included in the submission, but there is a reasonable justification for its omission, submitters are encouraged to provide that justification to FDA. FDA as well has discretion to issue a RTA or ask submitters to submit missing information should they deem it necessary for evaluation. A new 15-day clock starts upon receipt of the updated submission information. Or, should the submitter not provide a response to FDA requests within 180 days FDA will consider the 510(k) to be withdrawn and close the submission in the system. The completed checklists are considered part of the submission’s administrative file and will not be posted publicly.
It is important to note that FDA will not review an application until the applicable user fee has been paid and validated. Those submitters who receive a RTA or request for additional documentation need not repay user fees nor pay additional user fees prior to a rereview of their application.
As submitters are preparing their application, some important preliminary questions that should be considered are:
- Is the product a device (per section 201(h) of the FD&C Act) or a combination product (per 21 CFR 3.2(e)) with a device constituent part subject to review in a 510(k)? (If yes, a 510(k) is appropriate)
- Is the submission with the appropriate Center? (FDA encourages submitters, especially those who are less familiar with the 510(k) review program or who have novel issues to address, to either interact with the appropriate FDA review staff directly or seek counsel from a reputable consultant well versed in not only 510(k)s but other types of drug/device submissions to determine the center most appropriate for the application).
- Is there a pending Pre-Market Application (PMA) for the same device with the same indications for use? (Should there be an active PMA application for same device with the same indications for use, either by the same or a different submitter, FDA must determine which premarket review pathway applies and the appropriate processes for addressing the situation.)
As FDA reviews applications and check lists, they will provide an explanation for any missing elements that trigger a RTA. This will help the submitter to understand specifically which pieces of information are not present as they prepare their revised documentation. Unless FDA otherwise notes, the resubmission need only contain those missing elements, not a resubmission of the entire application, for a secondary review.
The process of 510(k) applications is lengthy and complicated, though the addition of pre-designed checklists by FDA should make the process easier for those familiar with the process. Even those who are experienced submitters are encouraged to have active communication with FDA either directly, through a reputable consultant or through a US Agent (should the submitter be a foreign entity). Clear communication and understanding of which elements are required as part of a 510(k) will make process from submission to eventual approval more seamless.
EAS can assist with reviewing your 510(k) dossier to determine if it contains the required documents needed to satisfy the FDA’s content expectations.
About the Author
Bryan Coleman, Senior Director for Pharmaceutical and Device Consulting Service,s has 24 years of experience in FDA Investigations, OTC pharmaceuticals and tobacco quality and compliance, including various management roles with responsibility for regulatory compliance, quality assurance and multi-site audits and FDA inspections management. Immediately prior to joining EAS, he was Senior Manager of Quality Programs and Projects at Altria Client Services in Richmond, VA. Prior to Altria he spent nearly 14 years as the Director of Quality and Compliance for Research and Development at Pfizer Consumer Healthcare. Bryan’s five years of FDA experience began as a chemist in the Buffalo District and later as a consumer safety officer (CSO/Investigator) with Baltimore District where he performed a wide variety of field inspection work, including inspections of finished pharmaceutical and API (Rx/OTC/Veterinary Medicines) firms for general GMP and PAI purposes, BIMO/GCP inspections, medicated animal feed operations, medical devices, cosmetics, food and dietary supplement manufacturing, packaging/labeling and distribution facilities, as well as product complaint and recall surveillance activities. Bryan was also a member of the FDA’s Foreign Inspection cadre for drug inspection work. He has practical industry experience with pharmaceuticals, medical devices, dietary supplements and tobacco products/processes in the areas of development, improvement and implementation of sound Quality Systems that are efficient, sustainable, and compliant with FDA regulations. He has also performed mock FDA inspections, gap-analyses, and contractor facility audits. In addition to his professional quality and compliance experience, Bryan has over 27 years of service with the Army National Guard in both reserve and active duty tours and is currently a Colonel serving as the Director of Joint Operations for the Virginia Army National Guard.
About EAS Consulting Group, LLC
While EAS Consulting Group celebrates its tenth year of service under the name EAS, it continues to carry on 55 plus years of leadership in providing regulatory consulting to the industries regulated by FDA and other federal and state agencies. Our network of independent advisors and consultants enables EAS to provide comprehensive consulting, training and auditing services to the dietary supplement, pharmaceutical, food, medical device, tobacco and cosmetic industries. Whether the need is assistance with general FDA or USDA regulatory compliance or more specific needs such as product development, New Dietary Ingredient submissions, FSMA regulation compliance, generic or customized compliance trainings, 483 responses, product market withdrawals or recalls, mock-FDA audits, expert witness services, GRAS & food additive issues, dietary supplement labeling compliance or the development of a detailed import strategy and policy, EAS, with its over 150 consultants, former FDA compliance officials and industry experts, is able to assist. With vast expertise in FDA’s policies and enforcement, EAS is the proven choice for assistance in FDA and other regulatory matters. www.easconsultinggroup.com.