Several years after the draft guidance was released, the U.S. Food and Drug Administration (FDA) recently finalized its guidance for in vitro diagnostic (IVD) companion diagnostic (CDx) products. Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health, called the final guidance “generally consistent” with the 2011 draft but said it provided some clarifications for industry. The need for guidance, the FDA says, stems from the now “more common” use of therapeutic products for which an accompanying test “is essential” for the therapy to meet its labeled safety and effectiveness claims—namely the identification of subpopulations of patients for whom the treatment will be effective or pose increased risk of serious, adverse events. Additionally, an IVD CDX would be deemed essential if treatment is adjusted based on response monitoring to achieve improved safety or effectiveness. “Inadequate performance of an IVD CDx could have severe therapeutic consequences,” the FDA warns in the final guidance. Thus, a risk-based approach will be used to determine whether premarket approval or 510(k) clearance is needed for the IVD CDx. The FDA clarified that “in most circumstances an IVD CDx and its corresponding therapeutic product should be approved or cleared contemporaneously by the FDA.” […]
Several years after the draft guidance was released, the U.S. Food and Drug Administration (FDA) recently finalized its guidance for in vitro diagnostic (IVD) companion diagnostic (CDx) products. Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health, called the final guidance “generally consistent” with the 2011 draft but said it provided some clarifications for industry.
The need for guidance, the FDA says, stems from the now “more common” use of therapeutic products for which an accompanying test “is essential” for the therapy to meet its labeled safety and effectiveness claims—namely the identification of subpopulations of patients for whom the treatment will be effective or pose increased risk of serious, adverse events. Additionally, an IVD CDX would be deemed essential if treatment is adjusted based on response monitoring to achieve improved safety or effectiveness.
“Inadequate performance of an IVD CDx could have severe therapeutic consequences,” the FDA warns in the final guidance. Thus, a risk-based approach will be used to determine whether premarket approval or 510(k) clearance is needed for the IVD CDx.
The FDA clarified that “in most circumstances an IVD CDx and its corresponding therapeutic product should be approved or cleared contemporaneously by the FDA.” Planning for this, the FDA hopes, will occur “at the earliest stages of development.” Cases in which contemporaneous development may not be possible include a novel IVD device for a new analyte, a new version of the device by a different manufacturer, or an existing device cleared or approved for another use.
Regulation of LDTs Coming
In addition to finalizing guidance for IVD CDx, the FDA simultaneously announced its congressional notification and draft framework on the regulation of laboratory-developed tests (LDTs), including LDTs for CDx. The agency must legally give Congress 60 days’ notice and a summary of any impending guidance for regulation impacting LDTs.
The coordinated announcements ignited immediate reactions and exposed a sharp divide in the testing industry between the interests of IVD makers and laboratories running LDTs. The lab industry has long questioned the FDA’s authority to regulate LDTs, which it calls a service, not a device, while the IVD interest supports FDA regulation of LDTs, which they say will level the playing field.
“AdvaMedDx welcomes the publication of the draft framework on a risk-based approach to the regulation of LDTs,” said Andrew Fish, executive director of AdvaMedDx, which represents IVD manufacturers. “These types of tests are increasingly being used to diagnose and guide the treatment of potentially life-threatening conditions, and FDA oversight of higher-risk diagnostic tests including CDx, regardless of the manufacturer, is essential to patient safety. . . . AdvaMedDx’s membership supports a modernized and flexible approach to the review process for diagnostics.”
In contrast, the American Clinical Laboratory Association (ACLA) urged the FDA to “exercise caution,” expressing concern that additional regulation could stifle diagnostic innovation and ultimately jeopardize patient access. ACLA supports any additional regulation of LDTs to come through expansion of the CLIA framework.
“The massive leaps in scientific and medical advancement that have occurred over the last quarter century have yielded a bounty of new tests created by highly trained physicians and clinicians that were not even imagined when CLIA was last updated in 1988,” said Alan Mertz, president of ACLA, in a statement. “To the extent that stakeholders have concerns about possible regulatory gaps under CLIA, ACLA has long supported enhancing the CLIA regulatory framework, rather than impose an additional layer of regulation based upon a different statute designed for manufactured products rather than laboratory testing.”
Takeaway: Despite lab industry concerns over regulation of LDTs, the FDA is moving forward with oversight plans.
