Post-Market Approval (PMA) Supplement

A Post-Market Approval (PMA) Supplement is a regulatory mechanism specific to the U.S. Food and Drug Administration (FDA) and is exclusively associated with major, high-risk medical devices that have already received primary FDA clearance.

In simple terms, a PMA Supplement is a formal supplemental application submitted to the FDA for review and approval before a manufacturer makes a change or modification to a Class III (high-risk) medical device that has already received initial Premarket Approval (PMA).

Its primary function is to demonstrate that the proposed change continues to provide reasonable assurance of safety and effectiveness, maintaining the same high standard of scrutiny as the original PMA.

The PMA supplement process is essential for regulating significant alterations to critical, life-supporting, or high-risk devices (Class III devices) after they are already on the market.

Mandatory Requirement for Changes Affecting Safety or Effectiveness

After the FDA approves an original PMA, the applicant shall submit a PMA supplement for review and approval by FDA before making any change that affects the safety or effectiveness of the device.

Changes requiring a PMA supplement include, but are not limited to, alterations in the following areas:

• Indications and Labeling: Implementing new indications for use of the device. Changes to labeling, unless they are editorial and do not affect safety or effectiveness.
• Design and Components: Changes in the performance or design specifications, circuits, components, ingredients, principle of operation, or physical layout of the device.
• Manufacturing Environment: Changes in the sterilization procedures or the use of a different facility or establishment to manufacture, process, or package the device.
• Product Integrity: Changes in packaging or extension of the expiration date of the device based on data obtained under a new or revised stability or sterility testing protocol that has not been approved by FDA.

General Submission Requirements and Review Process

The procedures and actions that apply to an original PMA application (§ 814.20) also apply to PMA supplements.

• Content: The information required in a supplement is generally limited to that needed to support the proposed change. It must include a separate section that identifies each change and explains the reason for the change.
• Format: PMA supplements must be submitted in electronic format.
• Review Timeframe: The time frames for FDA review of a PMA supplement are the same as those provided for an original PMA. For a major amendment (which a significant PMA supplement often constitutes), the review period may be extended up to 180 days.
• Special Summaries: A full summary, as required for an original PMA, is only required for supplements submitted for new indications for use of the device, significant changes in performance or design specifications, or when FDA specifically requests one. The supplement must also include information concerning pediatric uses if additional, readily available information has been acquired since the previous submission.

Alternative Submission Pathways

The FDA has established alternative pathways for certain types of changes, allowing manufacturers to avoid submitting a full, resource-intensive PMA supplement:

PMA Supplement Submission Types for Device Changes

Changes Being Effected (CBE) Special PMA Supplement

This submission is used for changes based on newly acquired information that enhances the safety of the device or the safety in its use. Examples include labeling revisions that add or strengthen a warning, precaution, or contraindication. The manufacturer may implement the change before receiving formal written FDA approval, as long as the supplement is clearly marked "Special PMA Supplement – Changes Being Effected," the filing is complete, and FDA has acknowledged receipt.

30-Day PMA Supplement

This type is used for specific categories of changes that the FDA has determined (through advisory opinions or correspondence) do not require a full 180-day PMA supplement review. The change may be placed into effect 30 days after the FDA files the supplement, unless the agency requests additional information or informs the manufacturer that the supplement is not approvable.

30-Day Notice (Manufacturing)

A 30-Day Notice is required for modifications to manufacturing procedures or methods of manufacture that affect the safety and effectiveness of an approved device. The manufacturer may begin distribution of the modified device 30 days after the FDA receives the notice, provided the submission adequately describes the change, summarizes the supporting data, and confirms continued compliance with the Quality System Regulation (21 CFR Part 820).

Periodic Reports (Post-Approval Reports)

Minor changes or modifications that do not affect the device’s safety or effectiveness can be implemented without prior FDA review or approval. These changes are simply described in the manufacturer’s required periodic (usually annual) post-approval reports. This pathway also applies to changes that are consistent with an FDA-approved Predetermined Change Control Plan (PCCP).

Analogy for Understanding

A PMA Supplement is like obtaining re-approval for a structural modification to a skyscraper (the Class III device) after the original construction permit (the PMA) has already been granted. Since the original structure is critical and complex, you cannot simply swap out a major support beam or add new floors (changes affecting safety/effectiveness) without submitting detailed blueprints and engineering data to the city (FDA). The supplement process ensures that every proposed alteration is documented, peer-reviewed, and proven not to compromise the overall structural integrity before the change is executed.

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