Regulatory glossary

PMA: Premarket Approval for Class III Devices

Premarket approval is FDA's most demanding device pathway, governed by 21 CFR Part 814. It applies to Class III devices, those supporting or sustaining human life, of substantial importance in preventing impairment of health, or presenting a potential unreasonable risk of illness or injury.

One difference separates it from everything else. A 510(k) argues that your device is substantially equivalent to something already on the market. A PMA argues, from your own evidence, that the device is safe and effective. There is nothing to point at. You have to prove it.

The three device pathways

• 510(k): substantial equivalence to a predicate. Class II, mostly.
• De Novo: novel, low to moderate risk, no predicate exists. Creates a new classification.
• PMA: Class III. Independent demonstration of reasonable assurance of safety and effectiveness.

Choosing between them is a classification question first. If your device is Class III by regulation, the choice has been made for you.

What a PMA contains

• Device description, including components, properties and principles of operation.
• Nonclinical laboratory studies: microbiology, toxicology, biocompatibility under ISO 10993, stress, wear, shelf life, and software where applicable.
• Clinical investigations: study protocols, results, adverse reactions, patient discharge and complication information, and statistical analyses. Most PMAs require a clinical study conducted under an IDE.
• Manufacturing information: methods, facilities and controls, sufficient for FDA to judge conformity with the quality system regulation.
• Proposed labelling, including instructions for use.
• A financial certification or disclosure for clinical investigators.

The manufacturing section catches sponsors out. A PMA is the point at which your quality system becomes part of the application rather than a separate concern.

Review, and the inspections

FDA's MDUFA goal for an original PMA is 180 review days, which is not the same as 180 calendar days: the clock stops when FDA asks a question and starts again when you answer.

Two inspections normally accompany the review:

Preapproval facility inspection against 21 CFR 820, because approval requires FDA to find the manufacturing adequate.

Bioresearch monitoring of clinical sites and sponsor records, verifying the data in the application actually exists as reported.

FDA may also refer the application to an advisory committee panel. Panels are public, and for a novel Class III device the panel meeting is often the event that decides the outcome.

Supplements

Changes after approval go through supplements, and picking the right type is most of the work:

• Panel-track supplement: a significant change in design or a new indication needing clinical data.
• 180-day supplement: a significant change not requiring a panel.
• Real-time supplement: a minor change, reviewed in a meeting or call.
• 30-day notice: certain manufacturing changes, effective 30 days after receipt unless FDA objects.
• Special PMA supplement, changes being effected: certain labelling or safety-related changes you may implement before FDA approval.

After approval

Approval is conditional in practice. Expect post-approval studies, annual reports, continued MDR reporting, and for some devices a condition requiring long-term follow-up. A PMA device carries a heavier lifetime obligation than anything cleared through a 510(k).