FDA: Manufacturers Failing to Comply with Postmarket Conditions of Approval

Seeking to protect the public health without hindering the movement of innovative technologies into the marketplace, FDA has long struggled to find the elusive balance between premarket and postmarket review of medical devices. In recent years, the agency has increasingly required the manufacturers of Class III medical devices to establish patient registries and reporting mechanisms or to undertake significant postmarket studies as a condition of approval (COA) for their premarket approval (PMA) applications.

Such requirements can be imposed even when companies have already conducted extensive clinical trials prior to submitting their product for approval. Earlier this month, for instance, FDA’s general and plastic surgery panel recommended that a PMA be granted for the silicone breast implant by Mentor Corp. (Santa Barbara, CA), but also suggested that the agency impose a number of conditions for postmarket monitoring. It remains to be seen how the agency will respond to the panel’s recommendations.

According to a recent FDA report, however, all of the agency’s hand-wringing over postmarket requirements may be for naught. Issued by FDA’s device center at the end of March, Center for Devices and Radiological Health Condition of Approval Studies as a Postmarket Tool for PMA Approved Cohort 1998–2000, reveals that medtech manufacturers have a dismal record of compliance with conditions imposed by FDA when approving PMA devices.

The report covers the period from 1998 through 2000, and focuses on 45 PMAs for which the agency required postmarket studies as a condition of approval. The 45 products represent 35% of the total of 127 PMA devices approved by the agency during the period covered by the report. The CDRH report found that only 19 (42%) of the required studies were completed or were proceeding on schedule.

Obtaining information about the postmarket studies of the other 23 companies required a significant amount of investigation. Through reviews of annual reports and a survey of lead reviewers, CDRH was able to account for the activities of 15 companies. For the most part, the information that the researchers obtained revealed that little or nothing had been done on the required studies. Two studies were not completed because the devices had been withdrawn from the U.S. market. No information about the required studies could be found for eight of the companies.

CDRH characterized manufacturers’ compliance with required condition-of-approval studies as “suboptimal,” and chided itself for lack of a tracking system for such studies. Such a situation, the report said, makes it “very difficult for anyone to obtain information on the studies or their status, unless that person has extensive knowledge of the individual products under study.”

Gliklich: Real-world commitments.

Experts admit that performance of required postmarket studies is important to FDA’s ability to approve new medical technologies. “Real-world experience with devices often differs from the experience encountered during preapproval trials,” says Richard Gliklich, MD, president of Outcome (Cambridge, MA), a firm that assists medtech companies in developing postapproval studies. “The commitment to study patients in the postmarketing phase is relied upon in making approval decisions.”

The report notes that CDRH has taken or recommended the following actions to “improve the tracking of COA studies and for improving manufacturer compliance with the terms of performance of studies agreed upon at the time of PMA approval.”

• Responsibility for tracking, designing, and evaluating COA studies has been transferred from the Office of Device Evaluation (ODE) to the Office of Surveillance and Biometrics, which has primary responsibility for monitoring the safety and effectiveness of products after they reach the market.
• Three additional epidemiologists have been hired to work with companies and ODE early in the PMA review process on the design of their COA studies. They also will help track and evaluate study results.
• CDRH plans to publish a draft guidance for industry and FDA reviewers to provide clear guidelines for the content, format, and due dates of COA study reports. Uniformity in reporting will help the agency track the status of studies.
• A new electronic tracking system has been put in place that will formally track the status of COA studies. Firms will be notified immediately if reports are overdue.
• CDRH will periodically report the results of COA studies to the center’s advisory panels.
• CDRH is considering posting periodic status reports on COA studies on the agency’s Web site.

Both FDA and the Centers for Medicare and Medicaid Services (CMS; Baltimore) have moved in directions or launched initiatives that rely heavily on postmarket studies. “On the safety front, FDA is clearly interested in expanding postmarketing requirements for both drugs and devices,” says Gliklich. “The agency’s recently released guidances on pharmacovigilance and RiskMAPs demonstrate the agency’s view that safety-signal detection and management in the postapproval period will be an increasing requirement for approvals. Further, FDA has made several recent announcements about changing its oversight of postmarketing activities.”

CMS has also moved forward with a draft guidance for the new determination status of ‘coverage under evidence development,’ released earlier this month. “This clearly shows that CMS will be increasingly interested in postapproval data collection as a required part of developing evidence to support national coverage determinations,” says Gliklich. “Recent activity by CMS in establishing registries for implantable defibrillators and PET scanning were preludes to this more-encompassing document.”

Although the CDRH report was not finalized until March of this year, preliminary results for the report were first submitted in April 2003. CDRH has not offered an explanation for the 23-month lag time in making its findings public. Noting that the final report is nearly identical to the earlier version, however, the New York Times speculated that CDRH may have decided to sit on the report because of its potentially embarrassing findings.

The final report observes that agency action on many of its recommendations is ongoing. However, the report is unclear about which recommendations are being acted on or the extent of the agency’s activities. Whatever actions the agency is taking, manufacturers that are required to perform COA studies can be sure that they will receive greater scrutiny than in the past.

“FDA is under great pressure to follow through on these postmarketing commitments,” says Gliklich. “Furthermore, other branches of the government, such as the Office of Inspector General, may be evaluating whether there are other avenues to enforce these commitments. For device companies, this means that commitments made will need to be met—and likely on more-defined time schedules.”

A copy of FDA’s report, Center for Devices and Radiological Health Condition of Approval Studies as a Postmarket Tool for PMA Approved Cohort 1998–2000, is available from the FDA Web site at www.fda.gov/oc/whitepapers/epi_rep.pdf.

© 2005 Canon Communications LLC

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