The authority of the US Food and Drug Administration (FDA) over laboratory-developed tests (LDTs) has been vague for decades — and an August 2020 announcement from the US Department of Health and Human Services (HHS) to address tests for the coronavirus disease 2019 (COVID-19) crisis was just one of the most recent attempts to clarify the roles of the regulatory agencies regarding these tests.1

“The FDA asserts that [the Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act] allows it to regulate lab-developed tests,” David Grenache, PhD, president of the American Association for Clinical Chemistry, told Cancer Therapy Advisor. “But FDA also says that since 1976, it’s used enforcement discretion and [it has] chosen not to regulate them.”

The Medical Device Amendments of 1976 established in vitro reagents as devices, thereby placing commercially developed tests and LDTs under the authority of the FDA. But then the final rule in 1977 stated that clinical laboratories — which develop and conduct LDTs — are not regulated by the FDA.2

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“That’s the conundrum,” Dr Grenache said. “Clinical laboratories are exempt from FDA regulations, [but] clinical laboratories create laboratory-developed tests, and the FDA says [it] can regulate those — so it’s very murky.” 

The recent HHS announcement, which precipitated from the demand for more COVID-19 tests, applies to all LDTs, including those used in the diagnosis and treatment of patients with cancer.

In the announcement, HHS instructed the FDA that, if the agency wants to regulate LDTs, it must go through the rulemaking process to earn the authority rather than through guidance documents, compliance manuals, website statements, or other “informal” issuances.1

The announcement stoked fear that regulatory oversight of LDTs has eroded. In a statement by the Association for Clinical Oncology, Monica Bertagnolli, MD, former president of the American Society of Clinical Oncology (ASCO), said that the organization has “concerns” that the announcement “puts the safety of cancer treatments at risk.”3

“The failure to develop reliable tests that perform as intended, could lead to patients receiving an inappropriate and potentially harmful treatment, or alternatively, not receiving a treatment that has the potential to be beneficial,” the statement reads.3

Experts in laboratory medicine, however, viewed the HHS announcement differently.

“[The HHS announcement] really doesn’t affect the existing laboratory operations for diagnosing cancer tests,” said Jonathan Myles, MD, pathologist and chair of the Council on Government and Professional Affairs at the College of American Pathologists, during an interview. “The HHS announcement did not indicate that the FDA does not have authority over LDTs.”

Dr Myles explained that the HHS announcement affects COVID-19 testing because prior to the HHS announcement, the FDA was going through the Emergency Use Authorization process, where laboratories had to submit data to be able to do to the test.

Dr Grenache echoed a similar interpretation, saying the HHS announcement “changes nothing” for clinical laboratories. “I’m not doing anything in my laboratory differently now than I was a month ago,” he added.

The concern that LDTs lack regulatory oversight and pose a harm to patients is far from new and may stem, in part, from a misperception of how LDTs are regulated.

Neal Lindeman, MD, a pathologist and medical director of molecular diagnostics at Brigham and Women’s Hospital, Boston, Massachusetts, told this publication that he often hears people say LDTs are the “Wild West,” and that no agency oversees how they are performed. “It’s absolutely not true,” he said.