Following the issuance of a final guidance, LDT manufacturers and associations representing their interests fear the cost to manufacture LDTs will skyrocket due to the need for clinical trials, which may stifle innovation and restrict effective patient management. The first step toward a resolution to this regulatory impasse is to gain clarity around the FDA’s requirements. Here is what life sciences companies need to know and expect given the impending active regulation of LDTs.

How the FDA Defines LDTs

Once known as “home-brewed tests,” LDTs are often created in response to unmet clinical needs. For example, a community hospital may need to quickly produce a test to control an unexpected viral outbreak. By the FDA’s definition, an LDT is “an in vitro diagnostic device that is intended for clinical use and designed, manufactured, and used within a single laboratory.”¹ This means that if a hospital creates an LDT, it must be entirely innovated inside of only that hospital. Over time, LDTs have expanded in their reach and are purchased by and shipped to nationwide laboratories and utilized across the country, far from where they have been generated.

Regulatory Pathways Available for Approval

According to the FDA, LDTs are considered devices under the Medical Device Amendments Act of 1976, which laid the framework for regulation of devices and, therefore, subjects LDTs to FDA regulatory oversight. The FDA’s proposed regulatory framework suggests that LDTs be classified based on risk of the proposed intended use and it describes a phase-in implementation approach for enforcement that spans 9 years. However, once the guidance is finalized some measures will take effect immediately, including the requirement of registration and listing of tests within 6 months of a final guidance.

FDA and CMS Task Force Coordinates Oversight of LDTs

In April, the FDA and CMS formed a task force to coordinate oversight of LDTs to

Identify areas of similarity between the FDA quality system regulation and requirements under the CMS administered Clinical Laboratory Improvement Amendments (CLIA)

Work together to clarify responsibilities for laboratories that fall under the purview of both agencies
Leverage joint resources to avoid duplication and maximize efficiency

The task force will identify similarities between both agencies’ regulatory requirements and will make them clearer and more consistent, including use of uniform terminologies and efficient use of resources. It will conduct education and outreach programs and host a webinar series on the agencies’ coordination efforts.²

Stakeholder Comments to Draft Guidance May Influence Final Guidance

The Senate Health, Education, Labor, and Pensions Committee is currently considering proposals on LDT regulation that may influence the FDA’s final guidance. For example, the Association for Molecular Pathology has shared a plan with the Senate, suggesting an update to CLIA regulations so that CMS can establish a public database that houses validation information on test procedures, employ third-party reviewers to ensure clinical and analytical validity of high and moderate risk, and create a standardized process to track adverse events.³ The Diagnostic Test Working Group has also designed a regulatory framework for a new category of tests, called in vitro clinical tests, which would share oversight responsibilities across the FDA, CMS and the states.

In such an environment, an informed manufacturer must prepare for a thoughtful and leveraged regulatory and reimbursement strategy. To discuss our solutions for the impact of LDT regulation, contact Lakshman Ramamurthy at LRamamurthy@avalere.com.

Click here to access our webinar, FDA’s Regulation of Laboratory Developed Tests-Where Do We Go Next?

1. Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), Draft Guidance. 2014

2. FDA Blog. FDA and CMS Form Task Force on LDT Quality Requirements. 2015

3. Association for Molecular Pathology. CLIA Modernization of LDPS: Proposal Overview. 2015