In the previous articles under the heading of regulation of the medical device market, we looked at how the registration procedure in the United States looks like in general, and also paid attention to the classification of medical devices and the pre-market notification procedure. This article will focus on devices of the third risk class, in particular, the premarket approval procedure (premarket approval = PMA).

PMA covers three groups of devices of the third risk class, the division of which is based on the period of circulation. An important historical date in this case is May 28, 1976. On this day, medical device amendments were signed and entered into force, within which the classification nomenclature of MD was introduced. Accordingly, the first group of products consists of those medical devices that were in circulation before the entry into force of these amendments. Preamendment Class III devices require a PMA only after FDA publishes a regulation calling for PMA submissions.

The second group of products includes those MD of the third class, the circulation of which began after May 28, 1976. And the third group consists of the so-called transitional devices, which until May 28, 1976 belonged to medicines, and after the aforementioned date became considered medical devices. The approval numbers for these devices begin with the letter N. An example of such a device is intraocular lenses (21 CFR 886.3600). For some devices of the transitional group, the risk class was lowered to the second.

The regulation governing premarket approval is located in Title 21 Code of Federal Regulations (CFR) Part 814, Premarket Approval of Medical Devices. In brief it is a process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices.

For examination, the applicant must submit to the FDA a dossier consisting of two main sections:

• Administrative;
• Technical (including preclinical and clinical studies). As a rule, a well-written technical part of the dossier determines whether an application for a PMA will be approved.

The preclinical part of the dossier should include information on microbiology, toxicology, immunology, biocompatibility, stress studies and other. More detailed information on preclinical studies in the form of FDA recommendations can be found on the official website of the organization.

Clinical investigations section includes study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the clinical investigations. When developing the documents of this section, applicant should be guided by the database of the official website of the FDA.

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References:

1. https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-approval-pma
2. https://www.fda.gov/medical-devices/premarket-approval-pma/pma-historical-background
3. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=814&showFR=1
4. https://www.fda.gov/media/113230/download
5. https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products