“Lab Developed Tests”: FDA to Ensure Reliability

By Sondra Forsyth

On July 31st 2014, the U.S. Food and Drug Administration took important steps to ensure that certain tests used by health care professionals to help diagnose and treat patients provide accurate, consistent and reliable results.

A release from the agency reported that the FDA is issuing a final guidance on the development, review and approval or clearance of companion diagnostics, which are tests used to identify patients who will benefit from or be harmed by treatment with a certain drug. Companion diagnostic tests are intended to aid physicians in selecting appropriate therapies for individual patients. These tests are commonly used to detect certain types of gene-based cancers.

Second, consistent with the requirements of the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), the agency is notifying Congress of its intention to publish a proposed risk-based oversight framework for laboratory developed tests (LDTs), which are designed, manufactured and used within a single laboratory. They include some genetic tests and tests that are used by health care professionals to guide medical treatment for their patients. The FDA already oversees direct-to-consumer tests regardless of whether they are LDTs or traditional diagnostics.

The release quotes FDA Commissioner Margaret A. Hamburg, M.D. as saying, “Ensuring that doctors and patients have access to safe, accurate and reliable diagnostic tests to help guide treatment decisions is a priority for the FDA. Inaccurate test results could cause patients to seek unnecessary treatment or delay and sometimes forgo treatment altogether. Today’s action demonstrates the agency’s commitment to personalized medicine, which depends on accurate and reliable tests to get the right treatment to the right patient.”

The companion diagnostics guidance is intended to help companies identify the need for these tests during the earliest stages of drug development and to plan for the development of a drug and a companion test at the same time. The ultimate goal of the final guidance is to stimulate early collaborations that will result in faster access to promising new treatments for patients living with serious and life-threatening diseases. This guidance finalizes and takes into consideration public comment on the draft guidance issued in 2011.

While the FDA has historically exercised enforcement discretion over LDTs (generally not enforced applicable regulatory requirements), today these tests may compete with FDA-approved tests without clinical studies to support their use. The LDT notification to Congress provides the anticipated details of the draft guidance through which the agency would propose to establish an LDT oversight framework, including pre-market review for higher-risk LDTs, such as those that have the same intended use as FDA-approved or cleared companion diagnostics currently on the market. The draft guidance would also propose to phase in enforcement of pre-market review for other high risk and moderate risk LDTs over time.

The agency intends to propose continuing to exercise enforcement discretion for low-risk LDTs, LDTs for rare diseases and, under certain circumstances, LDTs for which there is no FDA-approved or cleared test.
“With today’s notification of the agency’s intent to issue the lab-developed test draft guidance, the FDA is seeking a better balanced approach for all diagnostics. The agency’s oversight would be based on a test’s level of risk to patients, not on whether it is made by a conventional manufacturer or in a single laboratory, while still providing flexibility to encourage innovation that addresses unmet medical needs,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health.

The FDA also intends to publish a draft guidance outlining how laboratories can notify the FDA that they are currently manufacturing and using LDTs, how to provide information about their LDTs, and how they can comply with the medical device reporting requirements.

A provision in FDASIA requires the FDA to provide at least 60 days’ notice to Congress before the agency publishes for public comment any draft guidance on the regulation of LDTs. As such, the comment period will open at a later date when the draft guidances are published in the Federal Register and the public is alerted to the start of the comment period. The agency also intends to hold a public meeting during the comment period to collect additional input.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.