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Cyberonics Gets FDA Reversal

At odds with FDA concerning its alleged noncompliance with good manufacturing practices (GMPs), and denied approval of its Vagus Nerve Stimulation (VNS) Therapy System for the treatment of severe depression, Cyberonics (Houston) was going through some rough times with the regulatory agency.

Yet, in a decision that came earlier than many industry analysts had expected, FDA recently reversed its previous action and approved the VNS device for the treatment of depression.

In an all’s-well-that-ends-well world, that might be the end of the story. But wait. There’s more.

The Cyberonics story offers real-world lessons about the current status of harmonized industry standards and the international product approval process for medtech manufacturers. While the medical device industry has long sought a harmonized regulatory framework that would permit plant inspections and product approvals carried out by one agency to be recognized by others throughout the world, the experience of Cyberonics suggests there is still a long way to go before that goal is achieved.

In late December, Cyberonics received a warning letter from FDA regarding “nonconformities with current good manufacturing practice (CGMP) requirements of the quality system regulation for medical devices.” The warning followed an eight-week inspection of the company’s Houston production facility from July to September 2004, and Cyberonics’s response to the alleged deficiencies, which FDA characterized as “incomplete” and failing to address the “specific issues” raised during the inspection.

The Houston facility manufactures the Cyberonics VNS system, which is the company’s sole product. FDA approved the VNS system for the treatment of epilepsy in 1997. But in August 2004, the agency denied the company’s premarket approval (PMA) application to market the system for treatment-resistant depression, despite a positive recommendation from the agency’s neurological devices advisory panel in June.

Cyberonics CEO Cummins: All’s well that ends well?

After receiving the December warning letter, Cyberonics chairman and CEO Robert P. Cummins said he was disappointed with FDA’s actions, but pledged to work with the regulatory agency to resolve outstanding issues in a timely manner. In what Cummins described as a “detailed and comprehensive” letter to FDA dated January 21, the company stipulated its conformance with product design, validation and verification testing, complaint handling, and reporting procedures in accordance with FDA regulations and industry standards. The letter also identified corrective actions already implemented and additional quality systems planned for the future.

Meanwhile, Cyberonics continued to seek approval of the VNS system as a treatment for severe depression. In September, the company submitted a PMA supplement amendment. According to Cyberonics chief financial officer Pamela B. Westbrook, the company intended to “remain in a quiet period until such time as we receive FDA’s decision regarding depression approvability.”

That period ended on February 2, when FDA reversed its earlier decision. The agency’s approval permits Cyberonics to market the VNS system as a “long-term adjunctive treatment for patients over the age of 18 with chronic or recurrent treatment-resistant depression . . . that has not responded to at least four adequate antidepressant treatments.”

Cummins called FDA’s action a “landmark decision . . . and a major step towards providing millions of Americans suffering from chronic or recurrent treatment- resistant depression, their families, psychiatrists, and payers exactly what they desperately need—an FDA-approved, informatively labeled, long-term treatment option specifically for their lifelong and life-threatening illness.”

According to a company news release, FDA’s approval is conditional on “final labeling, final protocols for a postapproval dosing optimization study and patient registry, satisfactory compliance with quality system regulations (QSR), and satisfactory resolution of any outstanding bioresearch monitoring issues.”

Following satisfactory resolution of outstanding regulatory compliance issues, Cyberonics hopes to launch the VNS system as a treatment for severe depression by the end of May.

And what about the company’s status in the global marketplace?

In contrast to the regulatory hurdles and setbacks Cyberonics experienced in the United States, the company recently received renewed approval to market the VNS system as a treatment for both epilepsy and depression in all member countries of the European Economic Area, Canada, Australia, and other markets. Noting that the company had recently undergone a successful audit by its European notified body, Cyberonics vice president for regulatory affairs and quality Alan D. Totah said, “This successful audit demonstrates Cyberonics compliance with the ISO 13485:1996 quality system standards for medical devices and the Active Implantable Medical Device Directive.”

© 2005 Canon Communications LLC

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