In December 2018, the United States Food and Drug Administration (US FDA) published the final guidance on Manufacturing Site Change Supplements: Content and Submission. Replacing the 2015 draft guidance, the final guidance clarifies the responsibilities of medical device manufacturers who are willing to change their manufacturing site for an approved device.

What Is A Manufacturing Site Change Supplement?

A manufacturing site change supplement is a form of submission to the FDA informing about the manufacturing site change which may affect the already approved medical device’s safety and efficacy. It is a part of a premarket approval application (PMA) supplement also known as ‘180-day supplement’ submitted by medical device manufacturers. A PMA supplement is applicable to:

  1. All Class III device manufacturers (in the US) who already have an approved PMA or a product development protocol
  2. Companies manufacturing devices covered under the humanitarian device exemption (HDE) (HDE holders are required to submit a 75-day supplement)

The final guidance outlines specific circumstances under which a site change requires PMA supplement filing with the FDA. The guidance’s prime focus rests on the following details:

  • Situations under which a manufacturer should submit a PMA supplement
  • Documentation that should be submitted to the FDA with a site change supplement
  • Factors the FDA will consider when determining whether to conduct an establishment inspection prior to approval of a site change supplement

Manufacturing Site Change Supplement and The Information to be Submitted

A site change supplement should contain:

  • An updated description of the device
  • Details stating the nature and purpose of the site change
  • A list of manufacturing functions that will be performed at the proposed new site
  • A flow diagram identifying the individual steps involved in the manufacture, processing, packaging, or distribution of the device at the new site
  • Details on equipment and processes that will be affected by the site change
  • A list of standards (if any) that will be used in the manufacturing process (this applies to both national and international standards)
  • The process validation and revalidation master plan for the site, including validation procedures and protocols, and a list of processes at the new site that are not in the plans to validate, but will be verified by inspection and test
  • Procedures for environmental control and contamination control
  • A detailed explanation of how the inspection, measuring, and test equipment are routinely calibrated, inspected, checked and maintained

With the increasing number of warning letters being issued to manufacturing sites because of not following Good Manufacturing Practices (GMPs), there seems a dire need for extensive Regulatory scrutiny before declaring any change. Though the guidance elucidates manufacturers with instances that might be considered for submitting a manufacturing site change supplement, decoding and implementing all of them comprehensively might be challenging. To be absolutely clear about the Regulatory proceedings while submitting the change in the prescribed format, it is advisable for manufacturers to clearly discuss the requirements with a medical device expert. Go for accurate consultation for compliance.


Related Posts by Category