Premarket Approval (PMA)

Key facts

Legal basis

FD&C Act Section 515; 21 CFR Part 814

Required for

Most Class III medical devices

Standard

Reasonable assurance of safety and effectiveness

Statutory review period

180 days; total time is usually longer

Identifier

P followed by six digits; supplements add an S number

What is Premarket Approval?

Premarket Approval is the most stringent marketing application for medical devices in the United States. Under Section 515 of the Federal Food, Drug, and Cosmetic Act, a Class III device that is not eligible for another pathway cannot be legally marketed until the Food and Drug Administration (FDA) approves its PMA.

Class III devices usually support or sustain human life, are of substantial importance in preventing impairment of health, or present a potential unreasonable risk of illness or injury. Replacement heart valves and implantable pacemakers are typical examples.

Unlike a 510(k), a PMA stands on its own evidence rather than on comparison with a predicate device. Most PMAs rely on clinical studies conducted under an Investigational Device Exemption (IDE).

How the PMA process works

A PMA generally moves through these stages:

Related routes include the modular PMA, which lets sponsors submit sections as they are completed, and the Humanitarian Device Exemption (HDE), a separate application for devices for rare conditions that requires evidence of probable benefit rather than effectiveness.

• Pre-submission: sponsors often meet with FDA to agree on study design before running clinical trials under an IDE (21 CFR Part 812).
• Filing review: FDA checks whether the application is complete enough for substantive review.
• Substantive review: scientific, clinical, labeling and manufacturing review, sometimes with an outside advisory panel meeting.
• Inspection: FDA generally inspects manufacturing sites for quality system compliance before approval.
• Decision: an approval order, an approvable or not approvable letter, or a denial order.
• After approval: changes affecting safety or effectiveness require PMA supplements, and annual reports are required.

Why PMA matters

The PMA pathway shapes device economics and competition:

• Forecasting: PMA timelines and clinical trial costs are much larger than those for a 510(k), which shapes launch forecasts and valuations for device companies.
• Competitive barriers: followers generally cannot rely on substantial equivalence and must generate their own clinical evidence.
• Tracking changes: PMA supplement histories in the FDA PMA database show new indications, design changes and manufacturing site changes over time.
• Liability: in Riegel v. Medtronic (2008), the Supreme Court held that federal law preempts many state-law product liability claims about PMA-approved devices, a protection that does not extend to 510(k)-cleared devices.