Medical Device Premarket Approval and Postmarket Inspections - Part II: Implementation
This compliance program provides guidance to FDA field and CDRH staff for Premarket Approval (PMA) preapproval and PMA postmarket inspections and administrative/enforcement activities associated with PMAs. For purposes of this compliance program the term "PMA" will be used for not only the processing of original PMA applications and PMA Supplements, but also other various preapproval applications including: Product Development Protocols (PDP) and Humanitarian Device Exemptions (HDE). In addition, for purposes of this compliance program the term "manufacturer" may also refer to the manufacturer's designated contract manufacturers, sterilizers, and/or relabelers of the PMA device.
This is a continuing program, implemented on the basis of directed assignments made to the Field by CDRH.
PMA Preapproval Inspection
A PMA preapproval inspection is performed to assess a manufacturer's ability to design and manufacture the PMA device in accordance with the conditions specified in the PMA application and the requirements of the Quality System (QS) regulation. Prior to the approval of a PMA application, CDRH will typically issue an inspection assignment for manufacturing sites that are deemed necessary to be inspected. This assignment is issued after the manufacturer has demonstrated in its PMA application that both the design controls and the manufacturing processes and controls have been adequately established.
PMA Postmarket Inspection
A PMA postmarket inspection is typically conducted eight to twelve months after the PMA has been approved. This PMA postmarket inspection provides FDA with the first opportunity to evaluate the newly-approved product since it entered the marketplace. A PMA postmarket inspection also provides FDA with the first opportunity to assess a manufacturer’s compliance with the Medical Device Reporting (MDR) regulation, Corrections & Removal regulation, Registration and Listing regulation, and the Medical Device Tracking regulation (if applicable) for the PMA device, as these areas are not typically covered during a PMA preapproval inspection. This device-specific inspection is intended to assure that the manufacturer is making the device in accordance with the conditions specified in the PMA and that it complies with the requirements of the QS regulation, MDR regulation, Corrections & Removal regulation, Registration and Listing regulation, and Medical Device Tracking regulation.
Program Management Instructions
The following guidelines are suggested for implementing this compliance program:
PMA Preapproval Inspection
The assignment will be issued after the manufacturer has demonstrated in its PMA application that both the design controls and the manufacturing processes have been established. The assignment will identify the device to be covered and will have a specific reporting due date that must be met in order for the Agency to meet statutory deadlines for a decision on the application.
All assignments will be placed in the FDA Field Accomplishments and Compliance Tracking System (FACTS). The District Office or Office of Regulatory Affairs (ORA)/Division of Foreign Field Investigations (DFFI) will be notified electronically of the FACTS assignment number and a copy of the assignment memo will be attached to that e-mail.
The following information will be sent to the appropriate District Office/Investigator once the assignment has been entered into the FACTS database:
- the PMA manufacturing section,
- inspectional guidance, if any,
- PMA review memos
For foreign site assignments, all applicable PMA documents will be sent via e-mail to appropriate investigator as soon as the Office of Compliance (OC)/Field Operations Branch (FOB) is notified that an investigator has been selected and the inspection has been scheduled. The investigator may contact the CDRH reviewer if there are any questions regarding the information provided.
To facilitate communications with the firm on matters pertaining to the status of the inspection, the firm’s response to the 483, or the need for a follow-up inspection, the District Office should identify a contact person for each particular PMA inspection assignment. The investigator should give to the firm at the close out of the inspection name and telephone number of the contact person.
Note: Some PMAs may be granted “Expedited Review” status if the device offers a potential for clinically meaningful benefit as compared to the existing alternatives (preventative, diagnostic, or therapeutic), or when the new medical device promises to provide a revolutionary advance over currently-available alternative modalities. The granting of “Expedited Review” means that the application would receive priority review before other pending PMAs. Therefore, expedited PMA inspection assignments take a top priority when scheduling PMA preapproval inspections.
PMA Postmarket Inspection
An assignment for a PMA postmarket inspection of manufacturers including contract manufacturers, sterilizers, relabelers, remanufacturers, and/or specification developers will occur approximately eight to twelve months after a PMA or PMA Supplement for new or alternate manufacturing sites has been approved. The assignment will be issued by OC/FOB with an inspection due date range that is between eight to twelve months after PMA approval.
Note: PMA postmarket inspection assignments will not be issued to designated sterilizer firms that meet certain criteria. Refer to Section III.B.3. for further guidance.
All PMA postmarket inspection assignments will be placed in FACTS. The District Office or ORA/DFFI will be notified electronically of the FACTS assignment number and a copy of the assignment memo will be attached to that e-mail.
Once an investigator has been selected and the inspection has been scheduled, the District Office or ORA/DFFI should notify via e-mail the PMA postmarket coordinator at CDRHPMAPROGRAM@fda.hhs.gov, identifying the investigator that will be conducting the inspection and the start date of the inspection. Copies of any cover letters for any PMA supplements submitted by the firm since the PMA was approved will be sent to the investigator electronically for review prior to the inspection.
The postmarket inspection should assure that the manufacturer of an approved PMA device:
Is complying with the requirements of the QS regulation, MDR regulation, Corrections & Removal regulation, Registration and Listing regulation, and Medical Device Tracking regulation (if applicable) for the PMA device (Refer to C.P. 7382.845 for guidance).
Has an adequate change control system in place and has obtained FDA approval (via a supplement) for any significant change in device design, labeling, or manufacturing process that may affect the safety or effectiveness of the device.
Note: Any issues associated with safety and effectiveness of the device should not be assessed during the inspection; the relevant evidence should be collected and referred to CDRH for further follow up. Refer to Part III.B.2 for further discussion regarding the coverage of design controls.