Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of Class III devices. Therefore, these devices require a premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing approval.
Question 1:
In a case where the FDA rejects the proposal of a PMA and provides a letter to the applicant for a Non- Approval of their PMA proposal, the manufacturer is entitled to several options. These include:
- Resubmit the PMA. As an applicant, I may resubmit the PMA after amending the necessary information that was missing and will comply with the requirements of the application (“Denial of approval of a PMA”). For example when a device is being used in both adult patients and paediatric. But in this case, the application did not base any data that includes paediatrics. This may be a case where the applicant did not carry out a paediatric study or may have forgotten to include the information. If the information concerning paediatric data is missing they could amend the PMA application to add the information and data collected from the paediatric study. If the paediatric study was not conducted, the applicant may be required to work with the FDA in order to get an extra time on the IDE to conduct the paediatric studies and amend the information on the PMA to the requirements of section (“Denial of approval of a PMA”). When resubmitting a PMA am required to include in my original proposal a PMA reference number. In a case where they accept the PMA, the date used while the filling is the date when the FDA obtains my resubmission letter.
- Since am the one applying, if I reflect the Non-Approvable letter as a denial of the PMA proposal, am entitled to file a petition to the administration to reconsider the action (“Denial of approval of a PMA”). In the petition, I may appeal in form of writing which should be within a period of 10 workdays since the date when I received the receipt notifying me of the refusal to file the PMA. Through a petition, the commissioner in charge of the FDA may now review the matter of the applicant. 10 workdays after getting the request, the FDA will have an informal meeting and make a decision on whether to fill, which will be within 5 days after the informal meeting. In the petition am required to submit a brief description of the decision I would like to be reviewed and also the actions I expect from the review plus the factual statement of the legal grounds I base my petition on. For example, a Non-Approval from the FDA may be due to the safety of the medical device, in which the data that was provided did not provide proof it is secure and safe. If the FDA accepts to file the PMA, the date for filing will be when they agree to take the PMA for filing. When FDA doesn’t reconsider the decision, I may demand reconsideration of their conclusion from the Administrator of the Centre for Devices and Radiological Well-being, whose verdict is the final directorial action regarding judicial review. After the PMA report is acknowledged by the FDA, they now commence a substantive review of the proposal where they can now notify an applicant through major or minor deficit letters of the necessary information that is needed by the organisation in the completion of the review of the proposal. As an applicant, I may demand to meet with FDA within a period of 100 days during the filing of PMA so as to discuss the status of the review application.
Question 2:
The FDA can also reject filing a PMA for various reasons. Reasons that determine the refusal may include;
- In a case where the PMA does not cover each of the items that are obligatory under section 814. 20 or in a case where the recognised review regulation was not complying with CFR part 50 or 56 and if a justification for omitting an item is not adequate (“Denial of approval of a PMA”). The CFR has exact guidelines that an IRB must meet and requirements for agreeable subjects. For example, if the FDA were reviewing the PMA and they found out that the said consent procedure at some of the study sites was not in accordance with 21 CFR part 50 (“Denial of approval of a PMA”). In this case, the FDA may have realised that throughout the consenting process they did not explain the risks and benefits of the study or did not inform the subject that the device was under investigation.
- False statement. In a case where the PMA contains statements that are false concerning the material facts. When the FDA conduct a PMA review process and happen to come across information in the application that is not true (“Denial of approval of a PMA”). For example, the manufacturer may claim that the device was in accordance with ISO standards and that it was tested for biocompatibility and cytotoxicity but during the review of the data that was presented for the cytotoxicity the test came out negative and the statement was false. It can also be in a case where the PMA is not complemented with a statement that certifies or disclose the requirement of 21 CFR 54 financial disclosure by Clinical Investigation (“Denial of approval of a PMA”).
- A situation where the applicant has an incomplete Premarket Notice that relates to a similar device in which FDA failed to predetermine suppose the device is in line with the provision of section 814. 1(c).