FINAL THOUGHTS
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Glen Paul Freiberg, RAC, is the president of RCQ Consulting (San Diego), and is a member of the IVD Technology editorial advisory board. He can be reached at glenf92067@aol.com. |
IVD tests are medical devices defined under section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Although clinicians ultimately determine whether to use a medical device, the use of IVDs allows clinicians to determine how to use the test results as well. Unfortunately, rather than choosing and evaluating risk related to the IVD device itself, clinicians often focus only on test results and ranges.
Under the In Vitro Diagnostic Multivariate Index Assays (IVDMIA) guidance issued last year, FDA has stated the following with regard to risk:
IVDMIAs raise significant issues of safety and effectiveness. These types of tests are developed based on observed correlations between multivariate data and clinical outcome. Additionally, IVDMIAs frequently have a high-risk intended use. FDA is concerned that patients are relying upon IVDMIAs with high-risk intended uses to make critical healthcare decisions when FDA has not ensured that the IVDMIA has been clinically validated and the healthcare practitioners are unable to clinically validate the test themselves. Therefore, there is a need for FDA to regulate these devices to ensure that the IVDMIA is safe and effective for its intended use.
FDA’s statement is a defense of a fourth layer of patient protection. The first, second, and third layers are ensured by the physician, laboratory director, and Clinical Laboratory Improvement Amendment inspection process. Diagnostic tests cannot achieve clinical utility and actionable activity without successfully meeting all layers of protection. Therefore, the value of the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) guidance’s contribution to the patient is questionable.
Rather than expanding the reach of FDA into laboratory-developed tests, IVD manufacturers should encourage Congress to closely examine the European Union (EU) risk-based systems and consider eliminating the majority of OIVD review. Comparing the cost of the FDA process and the EU experience allows manufacturers and Congress to examine other options. Eliminating the majority of the OIVD’s review process could accelerate benefits to patients with little risk.
One possible change to the OIVD product review could be an expanded product exemption process. Specifically, FDA can assign a Class I exempt status to all tests that do not have hazard evidence, are intended for self-testing, or can be classified as one of the other categories in the EU IVD Directive (e.g., blood screening).
The IVDMIA guidance sends the message that current FDA management has no interest in reducing its regulatory control and that perceived risk requires increased regulatory control for laboratories. To initiate effective change, IVD review direction will need to come from a higher level (i.e., a new commissioner). Failing that, Congress would need to update the FD&C Act. Escalating U.S. healthcare costs provide a foundation for legislators and regulators to take a closer look at the EU model and reduce regulatory control for IVDs. The IVDMIA guidance, while well intentioned, demonstrates that significant cultural, legal, and regulatory changes are overdue.
Conclusion
The current U.S. general election race provides a timely opportunity to initiate legislative changes to reduce or remove OIVD clinical utility determinations in premarket submissions. Right-sizing government should play a role in the cost, safety, and utility discussion. IVD manufacturers can continue to participate in this process by working with AdvaMed (Washington, DC), Congress, and lobbyists to modernize the IVD regulatory process to resemble the European algorithm.
The elimination of the clinical utility determination and most IVD submissions will level the playing field between laboratory-developed tests and IVD manufacturers, and retain a sufficient framework for their product safety and intended use. While a diagnostic regulator can easily find an outlier to challenge this approach, the proposed changes will improve the consistency of diagnostic test results and reduce the need for laboratories to develop brand-specific tests, neutralizing concerns stated in the IVDMIA guidance.
