15 Jun Final FDA Guidance – Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act
The FDA Issued a final guidance on May 16, 2016 intended to provide assistance and clarification to manufacturers of devices subject to FDA postmarket surveillance orders. These orders are issued at the time of device approval or clearance or any time thereafter. Manufacturers are required to commence postmarket surveillance 15 months after the day the order is issued.
The guidance provides:
- an overview of section 522 of the Act
- information on how to fulfill section 522 obligations
- recommendations on the format, content, and review of postmarket surveillance plan submissions
The guidance applies to devices that require post-market surveillance, these include Class II or III Devices that meet one of the following criteria:
- Devices whose failure would be reasonably likely to have a serious adverse health consequence
- Devices expected to have significant use in pediatric populations
- Devices intended to be implanted in the human body for more than one
- Devices intended to be a life-sustaining or life-supporting device used outside of a user facility
- Devices that are “expected to have a significant use in pediatric populations.”
Types of Postmarket Surveillance
The following is table provided by the FDA summarizing the different types of postmarket surveillance designs used to address different public health issues presented by a device.
|Randomized Clinical Trial||Prospective study comparing the effects of one or more intervention(s) against a control group. Subjects are assigned randomly to one of the study groups.|
|Prospective Cohort Study||A study in which the subjects in a defined population are followed prospectively in time to assess the occurrence of outcomes of interest as they occur. Such studies can include one or more groups defined in terms of their exposure to a device.|
|Retrospective Cohort Study||A study in which the subjects in a defined population are followed forward in time; however, unlike a prospective cohort study, the data records documenting the device exposure and outcomes have been collected in the past relative to the time when the study is initiated. Such studies can include one or more groups defined in terms of their exposure to a device.|
|Cross-Sectional Study||A study in which the presence or absence of an exposure and health outcome are assessed at the same point in time.|
|Enhanced Surveillance||Continued monitoring of the distribution and trends in the incidence of adverse events through ongoing, passive but systematic collection, analysis, and interpretation of data. A passive approach to surveillance means that the organization conducting the surveillance does not contact potential reporters and leaves the initial reporting to others. The surveillance may be designed to collect information on events that are both MDR-reportable and MDR non-reportable adverse events or device complaints.|
|Active Surveillance||Continued monitoring of the distribution and trends in the incidence of adverse events through ongoing, active systematic collection, analysis, and interpretation of data. An active approach means that the organization conducting the surveillance initiates procedures to obtain reports. The surveillance may be designed to collect information on events that are both MDR-reportable and MDR non-reportable adverse events or device complaints.|
|Comprehensive, Linked, Registry- Based Surveillance||Registry-based comprehensive surveillance with shared responsibilities leverages the national registry infrastructure that is linked with other data sources (e.g., claims data) for longitudinal assessment of device performance. Embedded in the health care delivery system, this type of surveillance is characterized by shared responsibilities of multiple stakeholders (e.g., professional societies running the registries, FDA epidemiologists performing the surveillance analytics, payers assisting with linking to administrative data, and industry supporting the registries).|
|Meta-Analysis||Systematic review that combines the results of several studies that address a set of related research hypotheses. This is normally done by identification of a common measure of effect size, which is modeled using a form of meta- regression of the published or unpublished study data.|
|Prospective & Retrospective Study||A hybrid cohort study in which data are collected both retrospectively and prospectively.|
|Case Control Study||Study in which subjects are identified on the basis of the presence of an outcome (cases) and compared to an appropriate comparison group. The proportions with the exposure of interest are compared.|
|Bench/Lab Study||A study that involves bench testing (e.g., wear testing, fatigue testing).|
|Animal Study||A study that involves animal testing (e.g., device or material implanted in animal).|
|Other Design||A surveillance design that does not fit one of the other categories.|
Postmarket Surveillance Process
The FDA provides an overview of the process for how they identify issues and determine that a postmarket surveillance order should be issued to the manufacturer.
- FDA identifies issues that are appropriate for postmarket surveillance during the life cycle of a device. These issues are identified through a variety of sources:
- analysis of adverse event reports
- a recall or corrective action
- post-approval data
- review of premarket data
- reports from other governmental authorities
- review of scientific literature.
- The FDA assembles a review team to discuss the issue and determine if a 522 order should be issued.
- If the review team agrees that a 522 order is required, an order will be sent to the manufacturer including the following information:
- Postmarket surveillance (PS) number (PS######)
- premarket submission involved
- the public health questions posed by the device
- A rationale for the order
- Design recommendations to assist the manufacturer in preparing the postmarket surveillance plan
Postmarket Surveillance Plans
Once a manufacturer receives a 522 postmarket surveillance order, they are required to submit a postmarket surveillance plan within 30 days of receipt of the order. The FDA will review the plan and respond within 60 days. They will provide one of the following decision letters in response to the plan:
- Not Acceptable Letter
- Approval Letter
- Minor Deficiency Letter
- Major Deficiency Letter
- Disapproval Letter
It is recommended that manufacturers conduct early interactions with FDA to agree on plans or other issues. However, if within 6 months a manufacturer does not have an approved postmarket surveillance plan, the manufacturer’s plan status may be categorized as “Plan Overdue” on FDA’s website.
Supplements and Reports
Amendments, Supplements and Reports are required to be submitted under the Postmarket Survillience Order number. Please note, FDA may disclose the contents of the original submission and any amendments, supplements, or reports. When FDA discloses such information, FDA will continue to protect any trade secret or confidential commercial information, as well as any personal privacy information of patients.
- Changes to the PS Plan: A supplement should be submitted to the FDA if the manufacturer wishes to propose a change to an approved postmarket surveillance plan that will affect the nature or validity of the data collected, the manufacturer must obtain FDA approval in writing before making such changes.
- Interim Postmarket Surveillance Reports: An Interim Postmarket Surveillance Report is a written report to FDA on the status of the fulfillment of a postmarket surveillance requirement prior to its completion.
- Manufacturers should submit an Interim Postmarket Surveillance Report every 6 months for the first 2 years of the postmarket surveillance and annually, thereafter, from the date of the 522 postmarket surveillance plan approval or other negotiated starting date.
- FDA intends to complete the review of interim reports and respond within 60 calendar days.
- If FDA has questions regarding the data provided in the report, or the data are incomplete or insufficient, they will request additional information for the FDA approval.
- Final Postmarket Surveillance Reports: A Final Postmarket Surveillance Report is a written report of a terminated 522 order requirement or a completed postmarket surveillance.
- FDA recommends the Final Postmarket Surveillance Report be submitted no later than three months after study/surveillance completion
- FDA intends to complete the review of manufacturers’ submissions and respond within 90 calendar days.
- If the report raises new issues or questions, FDA may:
- request changes to the labeling of the device to reflect additional information learned from the postmarket surveillance;
- issue a new postmarket surveillance order to address new issues; or
- consider administrative or regulatory actions to protect the public health (e.g., device recall or request an update to a device’s indications for use statement)
Consequences of Failure to Comply
Failure to comply with a requirement under section 522, including failure to commence surveillance within 15 months of a 522 order, is a prohibited act. The FDA will render the device misbranded. Violations may lead to enforcement actions including seizure of product, injunction, prosecution, and/or civil money penalties. Thus it is crucial to pay close attention to postmarket requirements posed by the FDA.
Boston Biomedical Associates has extensive experience assisting companies in meeting Postmarket Surveillance requirements. We can help your company to understand what the FDA expects when they issue a 522 order, design an effective strategy for compliance, and guide your company through the execution process.