Pre-Market Changes

‍Pre-Market Changes are modifications, adjustments, or revisions made to a medical device, its intended use, or its documentation during the critical stages before it is legally introduced into commercial distribution, requiring formal regulatory submission and internal design control procedures.

In simple terms, a Pre-Market Change is any modification made to a medical device's design, components, or proposed use during the period when the device is under regulatory review (e.g., a pending PMA or 510(k)) or while it is actively being developed or investigated (e.g., under an IDE), and before it receives clearance or approval to be sold.

Teaching You About Pre-Market Changes

The management of pre-market changes involves strict internal controls (Design Controls) and specific external reporting to the FDA to ensure that the device remains safe and effective before its initial commercial release.

Regulatory Triggers for Submissions

Changes made prior to commercial distribution require formal submissions if they alter the scope of the device's original application or significantly affect its safety or effectiveness:

• Premarket Notification (510(k)) Requirement: A person required to register their establishment must submit a premarket notification (510(k)) at least 90 days before introducing a device into commercial distribution for the first time. This submission is also required for a device currently being distributed or reintroduced into commercial distribution that is about to be significantly changed or modified in design, components, method of manufacture, or intended use.
  • A significant change or modification requiring notification includes one that could significantly affect the safety or effectiveness of the device (e.g., a major change in design, material, energy source, or manufacturing process).
  • A major change or modification in the intended use of the device also requires premarket notification.
  • A device that was formerly marketed but has been substantially altered is classified by statute into Class III and requires Premarket Approval (PMA) before commercial distribution unless reclassified.
• Changes to Pending PMA Applications (Amendments): For high-risk devices undergoing Premarket Approval (PMA), a PMA amendment is information submitted to FDA to modify a pending PMA or a pending PMA supplement.
  • An applicant may submit an amendment on its own initiative to revise existing information or provide additional information.
  • FDA may request an applicant to amend a pending PMA or supplement with information necessary for the agency to complete its review.
  • The applicant must periodically update its pending PMA with new safety and effectiveness information learned from ongoing or completed studies that may reasonably affect the evaluation of the device. These updates are considered amendments.
  • If an applicant, on its own initiative or at FDA’s request, submits a major PMA amendment (e.g., containing significant new data or significant required information previously omitted), the review period may be extended up to 180 days. Failure to respond to an FDA request for a PMA amendment within 180 days results in the pending application being considered voluntarily withdrawn.

Changes During Investigation (IDE Supplements)

When a change is made to a device or its study protocol while it is still under investigation via an Investigational Device Exemption (IDE), specific requirements for supplemental applications apply:

• Changes Requiring Prior Approval: Except for certain exceptions, a sponsor must obtain approval of a supplemental application before implementing a change to an investigational plan.
• Developmental Changes with Notice: A sponsor may implement developmental changes in the device (including manufacturing changes) without prior approval if the change does not constitute a significant change in design or basic principles of operation and is made in response to information gathered during the investigation.
  • The sponsor must provide notice to FDA within 5 working days of making these changes.
  • For such a change, the notice must include a summary of relevant information, a description of the change, and, if design controls were used, a statement that no new risks were identified and that verification and validation demonstrated that design outputs met design input requirements.

Internal Design Control Requirements

Regardless of the regulatory submission pathway, all changes made to the device design prior to implementation must be controlled through the organization's Design Controls procedures (21 CFR 820.30), which are mandatory for most medical devices.

• Mandate for Change Procedures: The manufacturer must establish and maintain procedures for the identification, documentation, verification or, where appropriate, validation, review, and approval of design changes before their implementation. This procedure for design changes must be reviewed and approved by authorized personnel.
• Verification and Documentation: Design verification is performed to ensure that the design output meets the design input requirements. This confirmation must be documented.
• Quality Records: Records of design and development changes must be maintained. The process for requesting changes to a design must utilize a form or other media to create a quality record.

Analogy for Understanding Pre-Market Changes

Managing Pre-Market Changes is like meticulously revising the script and special effects of a blockbuster movie before it is released to the public or finalized for production. If the studio (manufacturer) decides during the filming process (investigation/review) to fundamentally change a character's storyline (intended use) or swap out a major special effect technology (design change), they cannot simply proceed. They must execute internal change control, thoroughly test and document that the revised scenes still achieve the intended safety and emotional impact (Design Verification and Validation), and formally submit the updated script and supporting evidence (PMA amendment or IDE supplement) to the film commission (FDA) for re-review and approval before the movie can officially be shown in theaters (commercial distribution).

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