U.S. Medical Device PMA Application Guidelines and Key Points

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Pre-market approval (PMA) is the most stringent route to market for medical devices in the U.S., and applies to most Class III high-risk devices, such as artificial heart valves, artificial joints, pacemakers, etc. Unlike the 510K, the PMA process is time-consuming and costly, and is significantly more difficult to obtain approval. The FDA requires the applicant to provide a series of non-clinical and clinical study data to support the safety and efficacy of the product. After passing the FDA's rigorous review process, the product can be marketed in the U.S.

Based on our experience in filing PMA for medical devices in the U.S., this article introduces in detail the PMA application guidelines and summarizes the key points of the application.

Introduction of PMA

FDA classifies medical devices into three categories according to their risk level: Class I (low risk), Class II (medium risk) and Class III (high risk). Failure of a Class III device can result in serious medical complications or even death for the patient or user.

To ensure the safety and efficacy of high-risk Class III devices, the FDA has adopted the most stringent regulatory control strategy, and most Class III products are marketed through a PMA. However, PMA certification is not required for all high-risk medical devices, and only for devices equipped with specific functions.

Applicants for a PMA are usually the developer or eventual manufacturer of a Class III device. The application materials for PMA usually include technical guidelines, product characteristics, manufacturing processes, safety data, inspection data, clinical trials and other information related to the product.

How to Apply for PMA

There are three types of PMA applications: Traditional PMA, Modular PMA, and HDE.

Traditional PMA

Scope: Products that have completed clinical trials or obtained marketing authorization in countries other than the U.S.

Submission: The applicant submits a one-time submission to the FDA.

Review: The FDA will conduct a review within a specified timeframe.

Features:

One-time submission of a large number of materials, including device description, intended use, non-clinical and clinical studies, case report forms, manufacturing processes, labeling, etc.

Modular PMA

Scope: Products with long R&D cycles and time-consuming clinical studies.

Submission: Applicants should divide the application data into several modules, such as production process, non-clinical study, clinical study, etc., and submit them separately.

Before submitting the modularized application, the applicant is required to submit a PMA overview to the FDA, describing in detail the content of each module to be submitted and the expected submission time.

Review: The review will be conducted in modules, and the FDA will provide feedback to the applicant on any deficiencies in the modularization information within 60 days of receiving the modularization information. The review process will be formalized upon completion of all modular submissions.

Features:

(1) FDA can provide timely feedback to the applicant on the review of each module.

(2) Relieve the pressure of the FDA to centralize the review of a large number of declarations.

(3) The number of modules is generally 3 to 4.

(4) This approach is not applicable to products whose design is in a state of flux or is likely to change.

Humanitarian Device Exemption (HDE)‍

Scope: Humanitarian devices are medical devices intended for use in rare diseases (diseases that manifest themselves in no more than 8,000 people per year in the United States).

Submission: The HDE pathway has the same requirements for submission, supplements, changes, and manufacturing quality systems as the PMA, and the HDE application can also be submitted in modules in accordance with the modular PMA requirements.

Review: Traditional PMA or Modular PMA.

Features:

(1) HDE has lower requirements for product validity than PMA applications.

(2) HDE can be reviewed faster than PMA, and the review is generally completed within 75 days of the initial review.

(3) HDE applications are free of charge.

Information and Data Requirements for PMA

A PMA application is a scientific, standardized regulatory submission to the FDA to demonstrate the safety and effectiveness of a Class III device. The PMA application contains administrative elements, but excellent scientific writing is key to approval of the PMA application. If a PMA application lacks the elements listed in the administrative checklist, FDA will deny the application and will not conduct an in-depth review of the scientific and clinical data.

An application that lacks valid clinical information and sound scientific analysis may jeopardize FDA's review and approval. Incomplete, inaccurate, inconsistent, or omitted critical information in a PMA application will result in delayed approval or denial of the application.

The technical components of a PMA include:

Non-clinical laboratory studies

Non-clinical laboratory studies include information on microbiology, toxicology, immunology, biocompatibility, stress, wear and tear, shelf life, and other laboratory or animal testing. Non-clinical studies used for safety evaluation must be conducted in accordance with CFR - Code of Federal Regulations Title 21 Part 58.

Clinical studies

Includes the study protocol, safety and efficacy data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, data listings for all individual subjects, results of statistical analyses, and any other information from the clinical study. It includes Form FDA-3674, which is proof of compliance with the Clinical Trials.gov database requirements.

Therefore, applicants should review the information before submitting the PMA application to FDA to ensure that it is scientifically sound and well-written.

PMA Review Process

PMA certification requires the manufacturer to submit all product-related data and test results, as well as the product's manufacturing quality management specifications, etc., and to conduct a rigorous and in-depth review of the submitted information.

For devices that require PMA certification, we recommend that manufacturers understand all of the PMA requirements in advance and ensure compliance with FDA regulatory requirements during the manufacturing process.

Materials completeness review
Substantive review
Panel Review
Final Decision

Communication channels

Early collaboration

FDA encourages applicants to contact FDA for further guidance before submitting a PMA application. This is especially beneficial for applicants who have not previously contacted the FDA and for applicants who intend to investigate new technologies or new uses of existing technologies.

Day-100 Meetings

An applicant may request a meeting with FDA within 100 days of submitting a PMA to discuss the status of the application, and FDA requires that an applicant request a 100-day meeting within 70 days of receiving notification of initial clearance.

Proregulations specializes in assisting medical device manufacturers in completing FDA PMA applications. If you are interested in our services or need more details, please contact us .