FDA PMA submission process: The ultimate guide
The US FDA has several approval and clearance routes that allow medical devices to be marketed in US territory. Based on risk-based classification, there are different possibilities. For the highest-risk class, class III, there is the Premarket Approval (PMA) route. In this article we dive deeper into what Premarket Approval means and how the process of PMA goes.
What is a Premarket Approval?
PMA is short for Premarket Approval. It's an FDA process of scientific and regulatory review to evaluate and assess the safety and effectiveness of Class III medical devices.
As these are high risk devices, FDA requires a PMA approval before allowing these products on the market. This PMA needs to contain sufficient valid scientific evidence to assure that the device is safe and effective for its intended use.
Does my device require a PMA?
Above, we mentioned that PMA requirements apply to class III devices. But what does that mean for your product?
"Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury."
Device product classifications can be found by searching the Product Classification Database. This database provides the name of the device, classification, and a link to the Code of Federal Regulations (CFR), if any. The CFR provides the device type name, identification of the device, and classification information.
All modern Class III devices require a PMA, however there is an exception for class III devices that have a suitable predicate device that was marketed prior to 1976. They may be eligible for a class III 510(k).
If you are unsure whether your device requires a PMA or not, you can search the Premarket Approval (PMA) database and the 510(k) Premarket Notification database using the three letter product code that belongs to your device. If there is a 510 (k) cleared by FDA and your device is substantially equivalent to this device, then a 510(k) is sufficient for your device.
Who can submit a PMA application?
Pretty much anyone can file a PMA application? Usually it is the person who owns the rights to the data and other information that is required for the PMA application, like the inventor/developer or the manufacturer. In case the applicant is not based in the US, the PMA must be countersigned by an authorized representative who does.
PMA Process explained
There are 4 steps in the review process of PMA applications:
Initial review: administrative and limited scientific review by FDA staff to determine completeness
Substantive review: in-depth scientific, regulatory, and Quality System review by appropriate FDA personnel
Panel review: review and recommendation by the appropriate advisory committee
Decision announcement: final deliberations, documentation, and notification of the FDA decision.
1. Initial review
The initial step after receiving a PMA application is an administrative review by the FDA. During this review, the FDA ensures that the application is complete and contains all the necessary documentation and data required for further evaluation according to the requirements of 21 CFR 814 and the PMA Acceptance and Filing Review Policy. This administrative review verifies that the application meets the regulatory requirements, including proper formatting, completeness of forms, and payment of applicable fees. Additionally, the FDA assigns a primary reviewer and establishes a review team consisting of experts from relevant disciplines such as clinical, engineering, and regulatory affairs.
Based on this review, the application will either be halted or will be accepted for further in-depth review. This decision is provided within 45 days after the FDA has received the application. If the FDA refuses the application, this is communicated to the applicant including the deficiencies in the application.
2. Substantive review
After the first initial review has been completed succesfully, the FDA will begin substantive review. Communication in this review phase is done via major/minor deficiency letters in which the FDA will require further information needed in order to complete the review of the application. The applicant may request to meet with FDA within 100 days of the filing of the PMA to discuss the review status of the application. This procedure is explained in the "Guidance on PMA Interactive Procedures for Day-100 Meetings and Subsequent Deficiencies - for Use by CDRH and Industry; Final"
The review period may be extended to 180 days if amendments are being made to the PMA which contain significant new or updated data.
3. Panel review
If needed, FDA may engage an outside expert panel, the advisory committee, to assess the safety and effectiveness of the device. This is only the case when there are no adequate in-house resources available. Also in this case, whenever additional information from the applicant is required by the advisory committee, this will be communication by the FDA.
4. Decision announcement
After reviewing the PMA application, FDA will communicate its decision. There are 4 possibilities:
Approval Order: this means the application is approved. Note that this is done on the basis of a draft label, which will still need to be finalized.
Approvable Letter: this means you're almost there and FDA believes it can approve the application if specific additional information is provided or specific conditions are agreed to by the applicant. When you receive an approvable letter, you have a few options:
Amend the PMA application as requested
Request an administrative review
Withdraw the application
Not Approvable Letter: the not approvable letter describes why the FDA believes it may not be able to approve the application. It lists the deficiencies in the application and what is necessary to make the PMA approvable. When you receive a not approvable letter, your options are:
Amend the PMA as requested. This will be considered a major amendment
Request an administrative review
Withdraw the application
Order Denying Approval
If the application fails to follow the requirements for PMA or if FDA has other grounds, FDA can deny the PMA application. The applicant will be informed about the deficiencies in the application.
What is the difference between a 510(k) and a PMA?
There are a few key differences between Premarket Approval (PMA) and Premarket Notification (510(k)):
Target device class: As described above, PMA is focused on high risk devices (class III). On the other hand, 510(k) clearance is focused on medium-risk devices (class II)
Principle of review:
The PMA process is about assessing the safety and effectiveness of your device and your device only. It doesn't compare with any other device. It's an in-depth review by experts that are going into all the details to assess and evaluate your device.
510(k) is only possible if there is a substantial equivalent device. This means that another device, similar to yours, has already been approved. The review of your application is that indeed the approved device is similar to yours and can serve as an equivalent device. Your data and information is compared to the known one and based on this your device might be cleared as well.
Duration: The PMA process takes up to 180 days, which is roughly double of the 510(k) process
Cost: There is a significant difference in cost between both the 510(k) process and the PMA process.
PMA applications are the most extensive review process for medical devices by the US FDA. They require a full set of documentation regarding your medical device as well as a well implemented QMS.
If you're curious to see how Matrix Requirements can help you in creating the right documentation for your PMA application, don't hesitate to book a demo.