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. |
The determination of clinical utility for IVD products has been a topic of interest among trade groups for many years. A previously published IVD Technology article (Commentary 1997) suggested that the ethics of determining clinical use for IVD tests should remain outside FDA’s jurisdiction. In March 2006, another IVD Technology article recommended that clinical utility determination should not be included in the FDA premarket review process. Little has changed in the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) review process for clinical utility since 2006; however, the laboratory industry has greatly increased the means and methods used to bring new tests to practitioners and patients without OIVD’s review.
OIVD has attempted to tackle part of the issue with a recent guidance issued last July, “Draft Guidance for Industry, Clinical Laboratories, and FDA Staff—In Vitro Diagnostic Multivariate Index Assays” (IVDMIA). From an OIVD perspective, this guidance clarifies that laboratory-developed or -manufactured assays meeting the definition of an IVDMIA will require OIVD premarket submissions at the end of a transition period. The guidance defines such laboratory-developed or -manufactured test kits as the following:
- Combines the values of multiple variables using an interpretation function to yield a single, patient-specific result (e.g., a “classification,” “score,” “index,” etc.) that is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, and
- Provides a result whose derivation is nontransparent and cannot be independently derived or verified by the end-user.
The new guidance also establishes the FDA submission time frame for such tests. The agency’s guidance states: “FDA intends to enforce regulatory requirements for all currently marketed laboratory-developed IVDMIAs that do not receive marketing clearance or approval within 18 months of publication of the final guidance document.”
Updating the Regulatory Landscape
Despite new requirements, many in the IVD industry are not convinced that FDA will begin enforcing compliance based on this time frame. On the contrary, some IVD manufacturers believe that the agency will continue its current discretionary enforcement process, which has been primarily directed toward significant advertising and promotional issues, the intention to make an example of a particular company’s test system, or based on complaints from a competitor regarding a potential health risk.
Some IVD developers doubt the FDA enforcement time frame because clinical laboratory staffs often lack the understanding to apply FDA’s quality system regulation (QSR) in the laboratory-developed-testing environment. While discretionary enforcement is generally understood as described above, clinical laboratories applying the QSR in a laboratory manufacturing environment, where staffs have little or no expertise with regulatory requirements, will be a challenge. Even in the case where the Center for Devices and Radiological Health issues a guidance on the subject, the time frame for implementation will be too short to coincide with the end of the IVDMIA grace period. Without concurrent FDA submission and QSR compliance, manufactured kits from industry and laboratory quality standards will remain quite different.
The added burden on the laboratories to preserve OIVD’s role in regulating the U.S. clinical laboratory testing market raises the question of the overall role of IVD premarket submission regulations. Most IVD tests in the EU and other nations are regulated by a self-certification process in which government approval prior to marketing is unnecessary. Although there are some exceptions to the self-certification approach (e.g., self-testing products such as home glucose monitors), no objective evidence indicates that the increased burden of the U.S. regulatory system provides any patient benefit. The cost of the regulatory submission process to secure FDA clearance or approval versus the EU system deserves further investigation in light of the overall cost to the American healthcare system.
