Key Strategies for Medical Device PMA Applications

About Premarket Approval (PMA)

Premarket Approval (PMA) is a regulatory approval path of FDA for Class III medical devices (the highest risk level), which is the most stringent pathway in the approval process for medical devices. PMA requires sponsors to submit substantial clinical data to support claims of device safety and efficacy.

Class III medical devices typically have the following characteristics:

• Supporting or sustaining life
• Important in preventing injury
• Permanently implanted in the body
• Unreasonably risky and/or lethal ‍

For more information about PMA, please visit: FDA Premarket Approval (PMA).

Premarket Approval (PMA) Application

In accordance with 21 CFR Part 814.20, the PMA application includes, among other things, the following:

• Description of the device's indications for use
• Detailed description of the device and its functional components or ingredients
• Reference to any performance standards or voluntary standards followed
• An environmental assessment in accordance with 21 CFR 25.20(n)
• The manner, facilities, and controls used in the manufacture, processing, packaging, storage, and installation of the device
• All bibliographies of published reports
• Device samples, if possible
• Copies of all the proposed labeling
• Copies of financial certifications or disclosures from clinical investigators
• Information on pediatric patients' use

The technical section is particularly important for clinical teams, involving preclinical and clinical studies, and must include:

Data from non-clinical laboratory studies: e.g., microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory or animal testing (if applicable).

Clinical study data: includes study protocols, safety and efficacy data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, summaries of all individual patient data, results of statistical analyses, and any other information from the clinical study.

Strategies for a Successful PMA Application

Considering the critical role of clinical data in a PMA application, it is important to plan ahead to ensure a smooth submission. Here are some strategies for a successful PMA application submission:

1. Engage with the FDA in advance

The FDA has made it clear that they encourage applicants to communicate with the FDA prior to submitting a PMA application to better understand the relevant regulations, requirements, and guidance documents. Early communication will help minimize delays in the process. Applicants can engage with FDA several times during the PMA application process through the Q-Submission program. Common forms of communication include:

• Pre-submission
• Information exchange meeting
• Study risk assessment
• Formal early collaboration meeting
• Submission issues meeting
• Day 100 meeting

2. Ensuring high quality study design

Clinical data is the cornerstone of a PMA application and determines whether a device will be approved, so it's critical to ensure that the study generating the clinical data is impeccable.

This means that the study population needs to be representative of the target user group, with clearly defined primary and secondary endpoints. At the same time, the entire clinical research process should follow Good Clinical Practice (GCP) standards, covering everything from study design to data management.

3. Use compliant, medtech-specific clinical data collection and management tools

One of the easiest ways to comply with GCP and FDA regulations on clinical data is to use an electronic data capture (EDC) solution that has been pre-validated to ensure compliance with all requirements.

Use only spreadsheets for all data can lead to data errors and non-compliance with the regulatory requirements of 21 CFR Part 11. If the data is not collected and managed in accordance with FDA requirements, it will not be accepted as critical evidence required during the PMA submission process.

4. Understanding PMA Amendments and Supplements

It is also important to familiarize yourself with the various PMA supplements and amendments, and in particular, to understand when to use each amendment. Key amendments include:

• Significant new data from previously unreported studies
• Significant updated data from previously reported studies
• Detailed new analyses of previously submitted data
• Significant and necessary information that was previously missed

As part of ongoing approval of the PMA, manufacturers are also required to submit an annual report within one year of the approval date. The report will identify any changes (PMA Supplement), as well as reports in the scientific literature on the device and unpublished data from any relevant clinical and non-clinical studies.

Typically, Class III devices take several years to design, develop, and test before a PMA application can be submitted to the FDA. Proregulations' team of experts delves deeper into the requirements of the PMA and the FDA's regulatory expectations, dedicated to assisting medical device manufacturers in navigating through the PMA process while ensuring the safety and efficacy of their products. If you are interested in our services or need more details, please contact us.