The present article describes in detail the aspects related to modifications to tests already approved for use in the US, as well as the ones related to the content of notification and reporting.
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to tests intended to identify the monkeypox virus. In particular, the guidance describes the approach the authority intends to apply in the context of the outbreak of monkeypox and the public health emergency associated thereto. The temporary and extraordinary regulatory measures described in the guidance are intended to ensure and expand the availability of monkeypox tests while ensuring the accuracy and reliability of the results they provide. By the virtue of the guidance, the FDA explains the way monkeypox tests could be used when the appropriate permission is granted under the accelerated procedure intended to reduce the overall time needed to make the tests available for actual use.
It is also important to mention that provisions of the guidance are non-binding, nor are intended to introduce new rules or impose new obligations, but rather to provide additional clarifications regarding the applicable framework, as well as recommendations to be considered by medical device manufactures and certified laboratories to ensure compliance thereto. The authority also reserves the right to review and amend the policy described in the guidance, should it be reasonably necessary based on the new information received by the authority to ensure public health protection.
The authority describes, inter alia, the aspects related to modifications to be made to the monkeypox tests that are FDA-cleared or authorized for use under the Emergency Use Authorization – a special framework intended to ensure the availability of vitally important medical devices without delays caused by a rigorous assessment while ensuring the proper safety, quality and effectiveness of medical devices it applies to. According to the guidance, when a high-complexity CLIA-certified laboratory is modifying a cleared or authorized monkeypox molecular diagnostic test, including one for which such laboratory is not the developer of the original test, and the modifications do not change the indication for use outlined in the 510(k) or EUA and do not change the analyze specific reagents, FDA does not intend to object to the implementation of the modification to the diagnostic test without a new or amended EUA or a new premarket submission where the test has been validated, the validation demonstrates that the modifications do not adversely affect test performance, and the laboratory submits a notification of validation to FDA. As further explained by the authority, in case modifications are made by the laboratory for a test that is not developed by the same laboratory, the such laboratory is encouraged to reach out to the original test developer and establish a data exchange since validation data could be required to support additional submissions and requests. In such a way, the authority expects the testing capacity will increase, as more laboratories will be able to use the test.
The FDA would also not object to modifications to the monkeypox test made by the medical device manufacturer, provided the indications for use remain without changes, and sufficient validation data is provided to substantiate the request related to the changes made.
As further explained in the guidance, FDA intends to notify developers by email if FDA declines to review, declines to issue, or otherwise decides not to authorize a supplemental EUA request for any reason, including lack of response or a determination that there is a lack of adequate data to support such request. In case such notification is provided, the parties involved should cease using the tests in question within 15 calendar days from the date the said notification has been issued. Furthermore, should it be identified that there are significant issues with the test, the party responsible for the tests should duly take all the steps to address the issues identified including, inter alia, initiating a recall, or issuing a notification to users informing them about an issue and describing the actions to be taken. Apart from this, the authority expects the test developer to publish information related to the actual performance of a modified test on its website, accompanied by a notice stating that this modification hasn’t been reviewed by the FDA.
The document further describes the content of notifications the parties involved should submit to the FDA via email. The information such notifications should contain would also be useful for the authority in terms of assessing the testing capacity. According to the document, the details to be included in the notification are:
- The policy of [the present] guidance for which [the applicant provides] notification;
- Laboratory name;
- Test name;
- Test methodology, including specimens type;
- Name of the laboratory director;
- Laboratory CLIA ID#;
- The date [the applicant] began, or intends to begin patient testing;
- Contact individual’s name, address, phone number, and email address;
- Estimated initial testing capacity (e.g., in tests per week);
- For notifications of modifications – the test name and developer of the FDA-cleared or authorized unmodified test and a short description of the modifications made to that test.
Once such notification is submitted, the applicant will receive an automated response confirming the safe receipt of the request and the appropriate number assigned to the notification to be used for future reference.
Reporting of Results
According to the guidance, it should be clearly stated in test reports that the question test has not been reviewed by the FDA (if applicable) – for transparency purposes. The authority additionally emphasizes that any statements that create an impression that the test is authorized by the FDA when it is not the case are strictly prohibited. Furthermore, laboratories should immediately notify appropriate Federal, State, or local public health agencies of test results by applicable laws.
In summary, the present FDA guidance describes the approach to be applied concerning modifications to monkeypox tests already cleared or authorized by the FDA. The document outlines the scope of modifications that would not require a new submission and also provides an overview of additional requirements related to the context of notifications and reporting.
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