- FDA issued final guidance Friday that clarifies the timeline a medical device maker should follow when submitting a premarket approval application (PMA) supplement following plans to change a manufacturing site.
- The guidance also explains what FDA considers to be a manufacturing site change. The recommendations apply to devices with an approved PMA, a product development protocol or a humanitarian device exemption (HDE).
- The document covers factors FDA will consider in determining whether to conduct an establishment inspection before approving the supplemental application. FDA said the guidance should help companies manage the time frames involved in implementing changes in the site and any processes, methods, procedures, qualifications and validations.
The Federal Food, Drug and Cosmetic Act requires manufacturers to submit a supplemental application to an approved PMA before making a change that affects a device's safety or effectiveness. The regulations require a PMA holder to submit a PMA supplement when it uses a different facility or establishment to manufacture, process or package the device.
A manufacturer should submit a PMA site change supplement that FDA reviews within 180 days of receipt. HDE holders are required to submit a 75-day supplement.
FDA said draft guidance for site change supplements, issued in 1999, was never finalized. The new guidance document, a draft of which was issued in October 2015, replaces that nearly 20-year-old document.
An alternative, for companies modifying a manufacturing procedure or method, is a 30-day notice. Changes that FDA believes may qualify for a 30-day notice, such as the addition of a new clean room to an existing manufacturing space, are covered in a separate guidance document, the agency said.
In the new guidance, changes to the manufacturing site that qualify for a supplemental application include those made to the processing, packaging or sterilization site of a legally marketed, PMA-approved device. Types of manufacturing site changes that affect device safety and effectiveness, according to FDA, include:
- Moving the manufacturing, processing or packaging for a finished device if the activities are not already conducted at the new site.
- Moving those activities to a manufacturing site that was not part of the PMA application or a supplement for the device.
- Moving manufacturing, processing or packaging for a finished device from a contract manufacturer to an in-house facility for activities not already conducted in house.
- Moving the activities into a nearby building with a different firm establishment identifier (FEI).
- Moving the activities to a contract manufacturer not approved as part of the PMA or a PMA supplement.