THE PREMARKET APPROVAL APPLICATION (PMA) -- FDC ACT §515

Premarket Approval Applications (PMAs) are required for all Class III and some Class II devices in order to give reasonable assurances of safety & efficacy. For the most part they will require human clinical trials, a good deal of money, and a much greater time commitment than any other type of device marketing application required by the FDA.

The PMA review is a four-step process consisting of:

  • Filing Review -- FDA staff conducts meetings, administrative checks and limited scientific review to determine whether a PMA is suitable for filing and further review. The agency will notify the company of the application's status within 45 days after receiving their PMA. The FDA has developed a checklist of refuse-to-file criteria to assist applicants in meeting threshold criteria;
  • Consideration -- FDA personnel conducts an in-depth scientific, regulatory, and quality system review;
  • Panel Review - Review and recommendation by the appropriate advisory committee;
  • Final deliberations, documentation, and notification regarding the FDA's decision.

COLLABORATION MEETINGS

The FDA Modernization Act provides for two early, formal collaboration meetings with the Secretary, scheduled only upon your written request. These one-day meetings are intended to provide clear direction for testing/development and will help you understand what will be required in order to get your device through the PMA process successfully. Prior to these meetings you must submit an extensive formal package. You should ask the Secretary about this package and begin its preparation as soon as you feel confident that you will bring a new device to market.

In essence, these meetings help you create a PMA Shell from which to structure the entire application. These meetings should not be taken lightly as agreements reached in these formal meetings are binding on both the company and the agency. It will be difficult for either party to deviate from the agreement after signing, so have someone at these meetings who is empowered to make critical decisions for your company as needed over the course of the day. By the end of these meetings the FDA should determine whether clinical studies are necessary to establish efficacy and, if so, how they should be conducted.

Other means of interacting with the FDA include phone calls and informal meetings, which may be useful prior to a formal meeting.

PMA STRUCTURE

A PMA can be viewed as a compilation of sections and modules that together become a complete application. The term module is used to identify a set of data and information addressing an aspect of the device. Information included in such a module ranges from pictorial representations of the device to clinical study data. A module may begin as the simple identification of the issue to be addressed and later developed into a detailed listing of the specific test results to be submitted. What is needed for each module will ultimately be decided by agreement between you and the FDA.

The PMA Shell is an outline of those sections or modules that will be necessary to complete the PMA. It will include all modules needed to support filing and approval of the total medical device. The FDA requires that the Shell be submitted in advance of the completed PMA.

As the information required for each module is reviewed and accepted by the FDA staff, the shell is filled with these completed modules. If you make any design or technical changes to the device after the module submission, you have to file supplements to the relevant module, identifying the changes and their effects. Once the module is complete and accepted by issuance of a status letter, it is considered closed and can only be reopened if there is good reason to do so. Once all modules are closed, the PMA is complete and can be submitted.

The filing date is the date that the FDA receives a complete PMA. The PMA may still be rejected for filing up to 45 days later. Technically, the FDA has 180 days from the day of filing to review the PMA and render a decision. In reality, the review will take longer, particularly since any substantial changes will restart the 180-day clock.

After the FDA notifies the applicant that the PMA has been approved or denied, a notice is published on the internet announcing the data on which the decision is based and providing interested persons an opportunity to petition the FDA within 30 days for reconsideration of the decision.

PMA SUPPLEMENTS

Making a change affecting the safety or effectiveness of the approved device requires filing a PMA Supplement.

Such changes include:

  1. New indications for use of the device
  2. Labeling changes
  3. Using a different establishment to manufacture, process, or package the devices
  4. Changes in sterilization procedures
  5. Changes in packaging
  6. Changes in performance or design specifications, circuits, components, ingredients, principle of preparation, or physical layout of the device.