Tips for Manufacturers Preparing for an FDA PMA Submission

This article provides valuable insights and practical tips to help manufacturers improve their chances of successful Premarket Approval (PMA) submission and facilitate the FDA review and approval process. By understanding the key requirements and recommended actions, manufacturers can better prepare their submissions, ensuring compliance with FDA regulations and ultimately bringing their innovative medical devices to market more efficiently. Whether you are new to the PMA process or looking to refine your approach, this article offers essential guidance to support your regulatory journey. 

As we have previously covered here, PMA device regulatory pathway established by the FDA is applicable to many high-risk and novel Class III devices and is more onerous than the 510(k) pathway for devices with a lower risk profile. 

Manufacturer Actions for Successful PMA Submission 

Understanding the PMA requirements established under 21 CFR Part 814 is crucial, but it is just the beginning. Manufacturers can take several proactive steps to enhance their chances of a successful PMA submission and streamline the FDA review and approval process. The main key actions that manufacturers can undertake to achieve these goals are listed below and discussed in more detail. 

Key tips for a Successful FDA PMA Submission:

1. Study Alternatives for the Same Indications for Use 
2. Familiarity with Relevant and Current FDA Guidance 
3. Meeting with the FDA and Eligibility for the Safer Technologies Program (STeP) 
4. Preparation of the Quality Management System (QMS) 

Study Alternatives for the Same Indications for Use 

While the PMA pathway does not require manufacturers to demonstrate substantial equivalency to a known predicate (a fundamental requirement under the 510(k) pathway), information of alternative practices and procedures still plays a critical role when preparing a PMS submission, including: 

• The Summary of Safety and Effectiveness (SSED), a required (publicly available) component of a PMA submission package, explicitly includes a section on alternative practices and procedures to be completed by the submitter. This section includes the advantages and disadvantages of all conventional procedures and practices for the desired indication, both medical and surgical, as well as legally marketed devices (it does not include investigational uses of devices). 

• While the PMA pathway is applicable for high-risk devices, the FDA still applies its “least burdensome” policy to these submissions, aiming to minimize the regulatory burden on manufacturers while ensuring device safety and effectiveness. For this reason, it is strongly recommended that manufacturers of non-novel high-risk devices review publicly available information for devices that fall within the scope of the same classification regulation / FDA product code available in the searchable PMA database. This information can be used to identify the non-clinical and clinical studies to be performed and the design of such studies, which have been used to support successful submission(s). As is the case with 510(k) submissions, where multiple PMAs exist, those that are more recent offer more relevant insight to successful approaches, as the expectations of reviewers do evolve over time, particularly in light of the state-of-the-art. 

Familiarity with Relevant and Current FDA Guidance 

In comparison to other regulatory agencies, the FDA has established a significant volume of guidance documents for industry and is widely considered the benchmark agency concerning the quality and scope of guidance provided. While manufacturers of devices subject to the 510(k) pathway are generally familiar with relevant FDA guidance, much of the same guidance, in addition to other guidance, may be equally applied in preparing PMA submissions. Therefore, it is critical that manufacturers familiarize themselves with relevant, current FDA guidance that may be applied to their PMA submissions. The following guidance is of note (in particular, guidance on benefit-risk determinations is critical given the importance of the benefit-risk determination in the SSED and PMA): 

• Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” (September 8, 2023) 

• General Considerations for Animal Studies Intended to Evaluate Medical Devices (March 28, 2023) 

• Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications (August 30, 2019) 

Use of the FDA eSTAR is currently voluntary for PMA submissions; however, links to relevant guidance are included under the Help Text Buttons embedded in the form. Therefore, manufacturers are encouraged to consult this resource to identify guidance relevant to submission components. 

In addition to guidance relevant to PMA submission compilation, as PMAs have additional post-market requirements, including specific change notification, post-market surveillance/reporting and post-market study requirements, manufacturers should also familiarize themselves with relevant post-market guidance, including: 

• Procedures for Handling Post-Approval Studies Imposed by Premarket Approval Application Order (October 7, 2022) 

• 30-Day Notices, 135-Day Premarket Approval (PMA) Supplements and 75-Day Humanitarian Device Exemption (HDE) Supplements for Manufacturing Method or Process Change (December 16, 2019) 

• Annual Reports for Approved Premarket Approval Applications (PMA) (December 16, 2019) 

Regulatory affairs and quality assurance departments can use information from such PMA process guidance to calibrate senior management expectations on the process itself, particularly regarding timeframes and necessary resources. 

Meeting with the FDA and Eligibility for the Safer Technologies Program (STeP) 

Given the nature of devices subject to the PMA pathway (i.e. life-supporting, sustaining and/or carrying a high risk-to-benefit ratio), irrespective of the device’s degree of novelty, it is strongly recommended that manufacturers intending to submit a PMA file a request for a Pre-submission (or Q-sub) meeting with the FDA, prior to submission. 

Where a manufacturer believes that its device is eligible for inclusion in the FDA’s Safer Technologies Program (STeP) for Medical Devices,  it is strongly recommended that a request for inclusion in STeP be submitted and managed through the Q-sub process. Devices included in STeP during review of the PMA submission may not benefit from programmatic features to the same extent as those devices for which requests for inclusion in the program occurred earlier during design and development (e.g. accelerated review timeframes due to greater agency interaction). 

The second eligibility factor criteria under STeP requires that the device should be reasonably expected to significantly improve the benefit-risk profile of a treatment or diagnostic through substantial safety innovations that provide for at least one of the following: 

• Reduction in the occurrence of a known serious adverse event 
• Reduction in the occurrence of a known device failure mode 
• Reduction in the occurrence of a known use-related hazard or use error 
• Improvement in the safety of another device or intervention 

Given the nature of the second eligibility factor, the relevant data to be included in the PMA submission to support STeP eligibility is of particular interest to the FDA. Hence, it is strongly recommended that the approach taken and data planned to support STeP eligibility be discussed with the FDA prior to submission. 

PMA applicants may request the following types of meetings with the FDA as part of a Q-sub or during the PMA review process: 

• “Determination” or Early Collaboration Meeting: Meeting held early in device design and development, which provides the applicant with the FDA’s determination of the type of valid scientific evidence that will be necessary to determine device effectiveness for its intended use. The FDA has a 30-day timeframe to provide a written determination following the meeting, which is binding, unless contrary to public health. 

• “Designation Request for Breakthrough Device” Q-sub: As part of this Q-sub process, this is a meeting held prior to submission to obtain the Breakthrough Device designation for a device. Such designation provides greater interaction with the FDA during device development (e.g. sprint discussions). Breakthrough Devices are not eligible for STeP (first eligibility factor criteria). 

• 100-Day Meeting: This is a meeting held with the FDA to discuss the review status of the application for which a request should be submitted with the PMA or as an amendment to the PMA no later than 70 days from FDA receipt of the PMA accepted for filing or 70 days from submission of the amendment making the PMA fileable (“filing date”). 

It is therefore important for submitters to establish a clear strategy regarding communication/interaction with the FDA prior to, during, and after the PMA submission, including any designations to be pursued. 

Preparation of the Quality Management System (QMS) 

In contrast to the 510(k) pathway, the PMA application process includes a review of manufacturing information for compliance with 21 CFR Part 820 (Quality System Regulation (QSR)). While manufacturers of devices covered by a 510(k) must also comply with QSR requirements (unless exempted under classification regulation) and may be selected for inspection by the FDA at any time, the FDA does not scrutinize the manufacturer’s QMS as part of the premarketing authorization. Therefore, readiness for FDA QMS review is a critical part of a manufacturer’s preparation for PMA submission. For organizations outsourcing their manufacturing processes, this includes ensuring that contract manufacturers and contract sterilizers are adequately prepared. 

As the February 2, 2026, effective date for the FDA’s Quality Management System Regulation (QMSR) is fast approaching, timing and preparations for transition to these revised QMS requirements are also crucial for manufacturers submitting PMAs. Subsequently, manufacturers should ensure that any potential impact on their PMAs by their transition is minimized. 

Learn More About FDA PMA Submissions with MedEnvoy 

This article touches on some tips for manufacturers to consider when preparing PMA submissions. MedEnvoy’s regulatory experts can assist manufacturers in staying compliant with the latest requirements, including compilation and submission of PMA applications to the FDA, and advising on PMA strategies. Furthermore, MedEnvoy has offices in the US, providing US Agent services. Please reach out should you need assistance by clicking here, and for information about our regulatory experts, click here. 

Related Resources