The FDA Premarket Approval process, commonly referred to as PMA, is the most rigorous regulatory pathway for medical devices in the United States. It applies to high-risk, Class III devices, which are those that support or sustain human life, are of substantial importance in preventing impairment of human health or present a potential unreasonable risk of illness or injury. For these devices, general and special controls are not sufficient to assure safety and effectiveness, and FDA approval is required before the product can be marketed. Understanding the PMA pathway is critical for manufacturers developing high-risk or novel technologies, as the process has significant implications for development timelines, clinical strategy, manufacturing readiness and long-term commercial viability.
What a PMA is
A PMA application is submitted under section 515 of the Federal Food, Drug and Cosmetic Act and is governed by 21 CFR Part 814. Unlike a 510(k), which relies on substantial equivalence to a predicate, a PMA is based on a direct demonstration of safety and effectiveness for the intended use of the device. The applicant must provide valid scientific evidence showing that the benefits of the device outweigh the risks when used as intended. PMA applicants are typically the legal manufacturers or entities that own or have authorised access to the clinical, preclinical and manufacturing data submitted in support of approval. FDA approval of the PMA must be obtained before the device may be commercially distributed in the United States.
Devices Subject to PMA
Class III devices are generally subject to PMA requirements. These include implantable devices, life-sustaining technologies and devices that play a critical role in preventing serious deterioration of health. Examples include many cardiovascular implants, neurostimulation systems and certain high-risk diagnostic devices. Some pre-amendment Class III devices may still be marketed through the 510(k) pathway, but for most new Class III technologies PMA is the default route. Correct classification is therefore a foundational step, as misclassification can lead to significant regulatory delays and rework if PMA requirements are identified late in development.
Pathways to PMA Submission
The FDA provides several pathways through which a PMA can be submitted, depending on the maturity of the technology and the development strategy. Before reviewing these options, it is important to recognise that each pathway still requires robust evidence and FDA approval before marketing.
- Traditional PMA:
- Most common route involves submission of a complete PMA application as a single, comprehensive package.
- Typically used when clinical investigations and supporting studies are complete at the time of submission.
- Modular PMA:
- Applicants submit sections of the PMA, known as modules, as they are completed.
- FDA reviews each module independently and provides feedback, which can reduce risk and spread review effort over time.
- Often used for complex devices with lengthy development programmes.
- The Product Development Protocol:
- Less frequently used option involves early agreement with the FDA on design and development activities.
- Once the FDA determines that the protocol has been completed as agreed, the device is considered approved
- Humanitarian Device Exemption (HDE):
- Applies to devices intended to diagnose or treat conditions affecting fewer than 8,000 individuals in the United States per year.
- Requires demonstration of safety and probable benefit rather than full effectiveness and is subject to additional conditions and limitations.
Key Contents of a PMA Application
A PMA application must comply with the detailed requirements set out in 21 CFR 814.20. The submission is extensive and must be carefully structured to support FDA review. Before outlining the main sections, it is important to understand that completeness and internal consistency are critical. Incomplete or poorly organised PMAs are a common cause of review delays.
A PMA typically includes applicant information and an executive summary, detailed indications for use, a comprehensive device description, and extensive scientific data. Scientific evidence includes results from bench testing, animal studies and clinical investigations, along with statistical analyses and study protocols. Manufacturing information must demonstrate that the device can be consistently produced to specification, and proposed labelling must accurately reflect the approved indications and risk profile. The Summary of Safety and Effectiveness Data provide a public-facing overview of the evidence supporting approval and is published by the FDA following approval.
Submission Format and Logistics
PMA submissions must be provided in electronic format, either as an eCopy or using the FDA electronic Submission Template and Resource (eSTAR). Submissions are made through the CDRH Customer Collaboration Portal and must be accompanied by a signed cover letter. Manufacturers must ensure that all required modules and attachments are included and that file naming, formatting and organisation meet FDA technical specifications. Administrative errors at submission can delay acceptance review and extend overall timelines.
FDA PMA Review Process
The PMA review process is multidisciplinary and interactive, with a standard review goal of 180 days for applications that do not require advisory committee input. The process begins with acceptance review, typically completed by Day 15, during which the FDA checks administrative completeness. This is followed by a filing review, usually completed by Day 45, which assesses whether the application is sufficiently complete for full scientific review.
Once filed, the PMA enters substantive review. During this phase, FDA reviewers conduct an in-depth assessment of the scientific data, manufacturing information and quality system compliance. This stage often includes preapproval inspections and bioresearch monitoring inspections of manufacturing facilities and clinical study sites. If deficiencies are identified, the FDA may issue information requests that pause the review clock until complete responses are received.
For certain devices, the FDA may convene an advisory committee panel composed of external experts. These panels review the evidence in a public meeting and provide recommendations to the FDA. When a panel review is required, the overall review goal extends to 320 days. The final stage involves FDA deliberation and issuance of a decision, such as approval, approvable with conditions, or denial.
Strategies for a Successful PMA
Navigating the PMA process successfully requires careful planning and disciplined execution. The FDA often summarises effective PMA strategy through three core principles. Being organised means submitting a well-structured, complete and internally consistent application that allows reviewers to locate and assess information efficiently. Being prepared means anticipating inspections, audits and detailed questions, and ensuring that manufacturing sites, clinical documentation and quality systems are inspection ready. Being responsive means answering FDA questions accurately, transparently and within specified timelines, and seeking clarification when feedback is unclear. Failure to meet these expectations is a common cause of prolonged reviews.
Post Approval Obligations
Approval of a PMA is not the end of regulatory obligations. PMA approved devices are subject to ongoing post-approval requirements, which may include post-approval studies, periodic reporting, manufacturing change controls and continued compliance with quality system regulations. Any significant changes to the device, manufacturing process or labelling may require submission of a PMA supplement and FDA approval before implementation. Effective lifecycle management is therefore essential to maintain compliance and market continuity.
LFH supports manufacturers throughout the PMA lifecycle, from early regulatory strategy and clinical planning to submission preparation, FDA interaction management and post-approval change control. Our team helps organisations navigate the complexity of PMA with clarity, rigour and confidence.
FAQ – FDA Premarket Approval
Is a PMA the same as FDA approval?
Yes, PMA results in formal FDA approval rather than clearance.
Do all Class III devices require a PMA?
Most do, although some pre-amendment devices may still follow the 510(k) pathway.
Can a PMA include clinical data from outside the United States?
Yes, foreign clinical data may be used if it meets FDA requirements.
How long does a PMA typically take?
Review timelines often range from one to three years depending on complexity and review interactions.
Can changes be made to a PMA approved device without FDA involvement?
No, most significant changes require a PMA supplement and FDA approval.
Is an advisory committee review always required?
No, it is required only when the FDA determines that external expert input is necessary.
