As a process by which the Food and Drug Administration grants approval to Class III devices, the premarket approval mechanism is the most rigorous type of approval the agency has.
As such, manufacturers of these devices should understand the process.
The Steps in a Premarket Approval
The premarket approval process occurs in four steps. The first step is a limited scientific review to determine completeness.
If the application is filed, the appropriate personnel will conduct an in-depth review of the scientific, regulatory, and quality systems. Then an advisory panel will review the submission and provide recommendations. The agency will then deliberate and provide a decision.
1. Limited Scientific Review
During the limited scientific review, the Food and Drug Administration will determine whether a submission is suitable to be filed.
They will determine whether a submission meets the appropriate requirements of the Federal Drug and Cosmetic Act and the Premarket Approval Acceptance and Review Policy. They will notify the manufacturer whether the premarket approval has been filed within forty-five days.
The Food and Drug Administration will refuse to file the submission if the application does not meet the minimum acceptable requirements. For instance, if the information is incomplete, unclear, or would not stand up to scientific scrutiny, the agency may refuse to file it.
The Food and Drug Administration will notify the manufacturer of the reasons why the submission was rejected and inform the manufacturer of what information is missing and what steps they need to take in order to make the application complete.
If the Food and Drug Administration refuses to file the application, the manufacturer can resubmit the premarket approval application with the additional information or they can request to have an informal meeting with the Food and Drug Administration.
This informal meeting would occur within ten working days. The agency will provide an answer as to whether they will file the application five days after the meeting. If the Food and Drug Administration files the application at that point, they will conduct an in-depth review.
2. In-Depth Review
The Food and Drug Administration will review the application after it has been filed. During the review, the manufacturer may receive letters from the Food and Drug Administration regarding deficiencies that the agency has discovered.
The manufacturer may also request to meet with the Food and Drug Administration one hundred days after the premarket approval application has been submitted to discuss the status of the application. If the applicant submits additional information, the Food and Drug Administration may lengthen the review period to up to one hundred eighty days.
3. Advisory Panel Review
If a device is the first of its kind, an advisory panel will review the application after the in-depth review is complete. This panel consists of experts independent of the officials at the Food and Drug Administration. This panel will hold a public meeting regarding the review of the device. During this process, the manufacturer may receive communications with the Food and Drug Administration regarding any questions that may arise. The advisory committee then submits a final report to the Food and Drug Administration that includes their recommendation and reasons thereof.
4. Final Deliberations and Decisions for Previously Unapproved Devices
On the basis of the recommendations provided by the committee, the Food and Drug Administration will issue one of the following: an approval order, an approvable letter, a not approvable letter, or an order denying approval.
If the Food and Drug Administration issues an approval order, the applicant must submit the final draft labeling. Then the Food and Drug Administration will approve the device and it is eligible for marketing. If the Food and Drug Administration issues an approvable letter, the agency will require the manufacturer to submit additional information.
The Food and Drug Administration will submit a not approvable letter if it cannot reach a decision because sufficient information is missing. A not approvable letter will describe the deficiencies and the reasons why the agency considers them deficiencies.
The Food and Drug Administration can issue is an order denying approval If the application does not conform to the appropriate conditions in the Federal Drug and Cosmetic Act, such as containing false statements or labeling that does not comply with the regulations.
They may also deny the application if the manufacturer does not allow them to inspect the facilities, Good Laboratory Practice violations are occurring and no explanation is provided, or ethics are being violated. They may also issue an order denying approval after issuing an approvable letter or a not approvable letter for any of the following reasons:
- The manufacturer provides the requested information but any other reasons for denial still exist.
- The manufacturer notifies the Food and Drug Administration that the information will not be provided.
- The manufacturer has requested an administrative review by filing a petition for the Food and Drug Administration to reconsider.
The order denying approval will describe the reasons for denying the application. The agency will place a detailed notice regarding the denial on the internet and then publish the notice in the Federal Register.
Decisions for Previously Approved Devices
The Food and Drug Administration can withdraw a device after it is approved if they find out that the device does not conform to the Federal Drug and Cosmetic Act, the manufacturer did not meet a postapproval requirement, or if ethics or Good Laboratory Practices are being violated.
In those cases, they will issue the manufacturer a notice of an opportunity to request a hearing. If the manufacturer does not respond or the Food and Drug decides to withdraw the device after the hearing is held, they will issue an order withdrawing approval and publish their decision in the Federal Register.
Recourse for Manufacturers
If the Food and Drug Administration has not issued an approval order, manufacturers have several options. In cases in which the Food and Drug Administration issues an approvable letter or a not approvable letter, the applicant can then supply the information, request an administrative review by filing a petition for the Food and Drug Administration to reconsider, or withdraw application entirely.
If the approval has been denied, the manufacturer can file a petition to reconsider.
Considerations for Manufacturers
One of the important aspects of the process is communication with the Food and Drug Administration. Manufacturers should communicate early and often with the agency.
Manufacturers considering submitting a premarket approval application should contact the Food and Drug Administration before they submit the application. Early communication will facilitate the process and minimize any possible issues.
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