FDA Issues 3p510K Guidance
On November 21, 2024, the US Food and Drug Administration (FDA) published its final guidance for manufacturers seeking to authorize low-to-medium risk devices through the Third Party 510K (3P510K) Review Program. The program uses qualified third parties to conduct initial reviews of 510K device submissions. The FDA’s guidance also describes the use of third party review organizations for Emergency Use Authorization (EUA) requests.
The goal of these third party review programs is to provide manufacturers with a potentially faster path to a decision for low-to-medium risk devices, while allowing the FDA to focus its internal resources on higher-risk and more complex devices. These programs are voluntary.
The guidance covers the eligibility of both third-party reviewing organizations and devices, the 3P510K and 3PEUA review processes, qualifications of reviewers, technical experts, and other personnel; the expected quality of reviews, guidance for avoiding conflicts of interest, and more.
Here are some of the highlights.
Guidance Regarding Third Party Review Organizations (ROs)
According to the guidance, third party review organizations should be independent and outside the federal government. Organizations should not be owned or controlled by a device manufacturer, supplier, or vendor, nor should they have organizational, material, or financial ties with these. ROs must also treat any information received through submissions as proprietary.
Determining Device Eligibility for Third Party Review
In determining which devices are eligible for third party review, the FDA considers the following:
The risks associated with the type of device
The complexity of the device type and the degree to which the device type is well understood
Whether the device is a combination product
If that device type raises novel cross-labeling considerations
Whether general controls are sufficient to provide a reasonable assurance of the device’s safety and effectiveness
If general controls are insufficient to this purpose, whether there is sufficient information to establish special controls to mitigate risks and assure the device’s safety and effectiveness
Whether the device type is intended for permanent implantation in the human body to sustain or support human life
Whether the information needed to make a well-informed recommendation is available to third party review organizations
Whether that information is proprietary
Whether consultation across different FDA organizational components is needed
If that device type requires review from another Center in the FDA
The complexity of the clinical data contained by the device type
The availability of postmarket data, such as a recall or a safety communication, that suggests the device type is the subject of safety signals
The Process for 3P510K Review
The guidance sets out the following process for 510K review by third party ROs:
Determine whether a submitted device is eligible for 3P501K review
If so, then a product specialist, and if necessary, a technical expert will be assigned
Obtain guidance and relevant information
Obtain early interaction consult if needed
Ensure submission is complete
Conduct and document the substantive review
Request additional information from submitter if necessary
Document the review and organize the submission
The final reviewer will then conduct the final review to finalize the submission
The 3P510K reviewer then submits the submission and their recommendation to the FDA.
How the 3PEUA Process is Different
The Third Party Emergency Use Authorization program arose from the COVID-19 pandemic. The large number of EUA requests for COVID-19 testing technologies made it clear that an additional review pathway for emergency use authorization was needed. The purpose of the 3PEUA Review Program is to allow the FDA to rapidly expand its resources to review EUA medical device requests if the Secretary of Health and Human Services makes an EUA declaration, that is, declares an emergency or threat justifying authorization for the emergency use of an unapproved product.
The 3PEUA review process differs from the 3P510K review process in a few critical ways.
First, a 3PEUA review may only occur after a declaration under section 564 of the FD&C Act has been made, justifying emergency use authorization of a product. The FDA will assign an EUA request to an RO at its own discretion.
Next, EUA submitters send EUA requests directly to the FDA, who may then send it to an 3PEUA RO for review. The FDA may decide, at its discretion, that public health would best be served if a given submitter sent the EUA request directly to the 3PEUA RO.
The FDA may contract with 3PEUA ROs directly, and may review requests sent directly to the RO.
The FDA will identify 3PEUA ROs based on the needed skills and experience in anticipation of, or at the time of an emergency declaration.
The FDA’s Expectations for the Quality of Third Party Reviews
The FDA expects third party reviewing organizations to conduct FDA-equivalent reviews of devices. Third party ROs are also responsible for analyzing scientific and technical data in their submission when making recommendations to the FDA.
The FDA further expects that:
A third-party reviewing organization will determine that they have the expertise necessary to review the device type, as well as whether that device type is eligible for 3P510K review. Likewise the RO should determine whether a review request is appropriate for third party review, even if the submission has come from the FDA.
Assigned product specialists will have appropriate expertise for the type of device under review. If the product specialist adds technical experts to the team, they should document the rationale for doing so. ROs should also identify a final reviewer within their organization who is independent from prior review of the submission. This reviewer will provide a final supervisory assessment of the product specialist’s work before the review is submitted to the FDA.
The guidance also specifies requirements for any external technical experts involved in the review, including said experts’ qualifications, expertise, and freedom from conflict of interest.
Third party ROs should be familiar with the publicly available information relevant to their review. 3P510K ROs should review the FDA’s postmarket databases to identify any issues with clinical use of similar devices that should be addressed in the review.
Submitters should fully inform third party ROs of any prior communications with the FDA about the device under review.
Third party ROs should make certain that their submissions are complete. The product specialist and final reviewer should be in agreement about the recommendation before submitting it to the FDA. If the final reviewer identifies any deficiencies in the submission, they should contact the submitter to resolve the deficiencies before making the submission.
ROs should document their reviews with a review memo specifying the reasoning behind their recommendations.
Preventing Conflicts of Interest
The FDA will examine potential third party review organizations for established, documented, and executed policies and procedures aimed at preventing conflicts of interest, including those pertaining to external technical experts.
In the interest of preventing such conflicts, the FDA recommends that third party ROs and their personnel not participate in the preparation of submissions. Moreover, ROs should not assign an individual to review submissions which that individual developed, helped developed, or prepared for submission. ROs should not assign any individual to review submissions who was employed by the submitter in the past twelve months.
Third party ROs should not promise FDA clearance or authorization.
You can read the full text at https://www.fda.gov/media/85284/download.