Medical device companies trying to understand what officially constitutes a manufacturing site change and when to submit a premarket approval (PMA) supplement will want to consult with draft guidance from the US Food and Drug Administration (FDA) released Tuesday.
According to FDA, the agency has received a number of questions on various scenarios that might require a device manufacturer to use a different site for manufacturing, processing or packaging a device. In some cases, FDA requires manufacturers to file a PMA site change supplement, which FDA has 180 days to review, while other scenarios would be considered a “modification to manufacturing procedures or methods of manufacture” that is eligible for a 30-day notice.
FDA offers two specific instances where a PMA supplement should be submitted: 1) when the site was not approved as part of any original PMA; or 2) when the site(s) was approved as part of an original PMA, but only for the performance of different manufacturing activities.
Under both of these circumstances, FDA says, the new site would have no experience with the process or the technology for manufacturing the same or a similar device, and FDA would not have had the opportunity to evaluate the change because it would not have been included in the original PMA application.
The agency also offers seven types of manufacturing site changes that affect device safety and effectiveness and require a PMA supplement, which includes moving the manufacturing, processing or packaging activities for a finished device into a nearby building or using a contract manufacturer not approved as part of the original PMA.
But certain changes in manufacturing sites "may be submitted as 30-day notices if they are among the sites already approved in a PMA, and if they are for performance of the same or similar manufacturing activities and for the same or similar device as those at the PMA approved site," FDA says.
In addition, FDA does not consider the use of a new facility or establishment for the manufacture, processing or packaging of a component of a finished device to require a PMA supplement.
As for scenarios when a 30-day notice should be used, FDA offers the example of an applicant that uses a contract manufacturer to perform sterilization activities for the applicant's cardiac stent system, but that applicant also performs sterilization activities in-house for a similar device and plans on terminating the contract with the contract manufacturer to conduct sterilization activities in-house for the cardiac stent system.
The draft guidance also includes what should be submitted in a PMA supplement and how FDA determines when an inspection may be needed.
As far as the inspections, FDA says it would likely inspect a new site if it lacks an inspectional history, or if an inspection occurred more than two years prior, or if FDA took action against a site following its inspection.
FDA Draft Guidance