FDA Update: Supplements for Approved Premarket Approval (PMA)

Supplements for Approved Premarket Approval (PMA) or Humanitarian Device Exemption (HDE) Submissions During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency

The FDA released a new guidance document on May 21, 2020 addressing manufacturing limitations or supply chain issues due to disruptions being caused by the COVID-19 public health emergency. This policy applies to limited modifications affecting the safety or effectiveness of a device approved through the PMA program that would require a manufacturer to submit a PMA supplement or 30-day notice to the FDA. This policy also applies to limited modifications affecting the safety or probably benefit of a device approved through the HDE program that would require a manufacturer submit an HDE supplement or 30-day notice to the FDA.

For the duration of the COVID-19 public health emergency, the FDA does not intend to object to limited modifications to the manufacturing of devices approved through the PMA or HDE program, without the prior submission of the required supplement or 30-day notice, where the modification does not create an undue risk, and is necessary to address the current manufacturing limitations or supply chain issues. This also applies to the changes to performance or design specifications, circuits, components, ingredients, or physical layout of the device which would require that a 180-day or real-time PMA supplement or a 75-day HDE supplement.

The circumstances where the FDA currently believes a modification would generally not create such an undue risk, that may be needed to address the current manufacturing limitations or supply chain issues include:

Changes that generally would require a PMA or HDE supplement:

• Component changes due to supply interruption of the component as a result of COVID-19 and any necessary software or firmware modifications to accommodate such component changes that do not affect the performance of the device
• Device material changes due to changes in manufacturing methods that do not affect the performance of the device

Changes that generally would require a PMA or HDE 30-day notice:

• Supplier changes to maintain continuity in manufacturing where specifications are unchanged
• Equipment changes to allow for processes to perform in equivalent manner to previously approved processes within the same facility
• Changes to accommodate social distancing, such as modification of manufacturing processes to promote social distancing practices among employees/operators
• Automation of existing processes that are fully verified
• Automation of certain processes, such as packaging and labeling processes to accommodate social distancing
• Addition of manufacturing lines to increase capacity in existing facilities approved as part of an original PMA or HDE application or a supplement

Changes that generally would require a PMA or HDE site-change supplement:

• Change in manufacturing facility or establishment to an alternative site with established good manufacturing practices (i.e., compliance with 21 CFR Part 820) or during the public health emergency, to an alternative site that is ISO 13485 certified.

Examples of circumstances the FDA believes a modification would create such an undue risk:

• Changes to the intended use of the device, including new indications for use of the device
• Changes to the labeling of the device, that are outside of the scope of recommendations described in other policies for specific devices during the public health emergency
• Changes to the sterility assurance level (SAL) or sterilization method
• Changes to reduce or eliminate quality control testing
• Automation of a manufacturing process that is not fully verified
• A change that affects the performance of the device, but is not caused by component unavailability

The FDA states that manufacturers must document any changes to the device in their device master record and change control records as well as make the information available to the FDA. The policy also states that it must be consistent with 21 CFR 820.30 and 820.180. Such records may include:

• Applicable standards to which the component conforms
• Software/firmware verification and validation
• Functional testing
• Mechanical testing
• Temperature testing

Manufacturing and design changes must be performed in accordance with 21 CFR Part 820. In the next period report due after the modification, in accordance with the PMA or HDE approval order, the FDA recommends that the holder identify and describe any such modification.

If you or your company is undergoing manufacturing limitations and need to make modifications to your device, mdi Consultants can assist you in understanding the requirements in order to assure compliance with the FDA guidelines and regulations in accordance with this new guidance document. Please email [email protected] RE: Device Modifications.