CEO SUMMARY: News stories about the FDA’s stated intention to regulate laboratory-developed tests (LDTs) generally play up the agency’s comments about the need to assert regulatory oversight of genetic tests and direct consumer access testing. But what has gone unremarked by the lab industry press is the simple fact that, if the FDA were to regulate all LDTs, many of the established lab tests run daily by the nation’s clinical labs might immediately fall under those new FDA regulations.
JUST AS RIP VAN WINKLE SNOOZED while Sleepy Hollow grew, so are many laboratory professionals across America unaware of how the FDA’s declared intent to regulate laboratory-developed tests (LDTs) has the potential to disrupt the daily clinical routine of almost every laboratory in the nation.
That is a powerful statement and is likely to catch most pathologists and laboratory administrators by surprise. That’s because, if the Food and Drug Administration (FDA) were to enact strict regulation of all laboratory-developed tests—commonly called “homebrew tests”—performed daily in this country, it would be immediately disruptive to long- established clinical lab testing activities.
After all, the conventional Pap smear is an LDT. That is equally true of FISH testing, flow cytometry, and many infectious disease assays. These are examples of LDTs that have been around for decades and have wide clinical acceptance. Yet, if the FDA ends up regulating all tests currently classified as an LDT and in common clinical use, assays like those listed above would immediately come under regulation.
Probably not since the passage in 1988 of CLIA (the Clinical Laboratory Improvement Amendment), has a single government agency embarked on a regulatory path that could be directly disruptive to nearly every laboratory now serving patients in the United States. For this reason, it is essential that pathologists and laboratory administrators understand the probable consequences of FDA regulation of laboratory-developed tests.
This summer, on July 19-20 in Hyattsville, Maryland, the FDA convened a two-day public meeting on oversight of laboratory-developed tests. More than 700 people—an overflow crowd—showed up to participate in the meeting and many more watched the events via a webcast.
FDA Regulation of LDTs
Much of the attention during this public meeting dealt with the rapidly-expanding field of molecular diagnostics and genetic testing. Many companies developing and offering proprietary molecular and genetic tests use the laboratory-developed test exemption. The FDA is on record as stating that it has the statutory authority to regulate these tests.
However, even as the public discussion centers on how the FDA would plan to regulate molecular and genetic tests, there are wider consequences to such regulatory actions that have the potential to be disruptive to every academic center lab, clinical lab, and pathology group in the United States currently performing high-complexity testing. Comments made during the FDA’s two-day public meeting, along with interviews with knowledgeable experts, reveal at least three key issues of concern associated with the FDA’s proposed regulation of LDTs.
First, as defined under current law, LDTs cover a wide spectrum of lab tests. The emerging class of molecular and genetic assays is frequently the subject of comments made by FDA officials as they discuss the need for regulatory oversight. The lab industry generally recognizes how FDA regulation of this sector of laboratory testing could prove burdensome and impede progress in this field of medicine.
The second key area involves academic centers. What is seldom publicly acknowledged by the FDA is that LDTs as defined today also cover the entire range of laboratory tests that are developed in academic centers and used regularly in clinical settings.
FDA regulation of these types of assays would create new regulatory hurdles. At a minimum, this would raise the cost of conducting the immense amount of research and development (R&D) that regularly produce new and powerful diagnostic assays. At a maximum, such regulation could create serious roadblocks that might discourage academic center labs from maintaining R&D efforts at or above current levels.
The third key area of concern is equally significant to all pathologists, Ph.D.s, and other types of laboratory scientists. As mentioned earlier, many lab tests used daily in clinical labs are LDTs, such as the conventional Pap smear. This class of assays has a long history of physi- cian acceptance and clinical use.
On the Web site www.labtestsonline.org, laboratory-developed tests are described. The web site tells consumers that examples of LDTs include “microscopic examinations (such as Pap smears and manual cell counts), erythrocyte sedimentation rates (ESR or sed rates), microbiology cultures and susceptibility tests, examination of tissue sections (including staining protocols), and blood cross-matching procedures.”
Were FDA officials to successfully assert regulatory authority over this menu of LDT tests, it would immediately become an important new regulator of almost every laboratory in the United States that provides testing to patients. In this way, FDA regulation of LDTs has the potential to be disruptive to almost every clinical laboratory and pathology group— large and small—across the country doing high-complexity testing.
It is this far-reaching aspect of FDA regulation of LDTs that has yet to catch the attention of the working pathologist and laboratory scientist. During the course of their careers lasting decades, these pathologists, Ph.D.s, and other types of laboratory scientists have performed these tests daily in support of long-accepted patient-care protocols.
In the coming months, it is expected that the FDA will issue proposed regulations on the subject of laboratory-developed tests. This will open up a period for public comment.
As that happens, laboratory administrators and pathologists may want to educate their entire laboratory staff to this issue by circulating the FDA’s proposed regulations around the lab. It would also be productive to encourage individual laboratory staff members to send com- ments about the proposed regulations to the FDA.
Finally, once the FDA issues a concrete proposal on how it plans to regulate LDTs, this is likely to immediately become a high-profile issue across the laboratory testing and biotech industries.
FDA’s Intent to Regulate Homebrew Lab Tests Has Potential to Touch Every Clinical Lab in U.S.
BY PROPOSING TO REGULATE THE ENTIRE CLASS of tests that fall under the laboratory-developed test (LDT) exemption, the Food and Drug Administration is embarked on what seems to be the largest expansion of federal oversight of laboratory testing activities since passage of the Clinical Laboratory Improvement Amendment back in 1988.
LDTs, also called “homebrew” tests, are performed daily in almost every clinical laboratory and pathology group in the United States. Thus, regulation of this class of laboratory tests has the potential to disrupt patient care in a number of serious ways if the final regulations are not crafted carefully.
Facing FDA regulation of LDTs, different sectors of the laboratory testing industry are lining up to lobby in favor of their interests. For example, in vitro diagnostic (IVD) manufacturers are required to clear their instrument systems and lab test kits through the FDA. They argue that a biotech company which launches a proprietary lab test under the LDT exemption has an unfair advantage and should be required to meet similar FDA requirements as are required of laboratory test kits.
For their part, biotech companies like the status quo. They are expected to lobby in favor of minimal regulation of their laboratory-developed tests. To date, this exemption has allowed this class of companies to introduce new assays into clinical use without having to undergo the expensive and time-consuming process of obtaining FDA clearance.
On behalf of the pathology profession, the College of American Pathologists (CAP) is advocating a tiered approach in its meetings with the FDA. It proposes three tiers based on risk: low, moderate, and high. It recommends that the FDA only regulate tests in the high-risk category. CAP suggests that moderate- risk tests could be reviewed by the laboratory’s accreditor (which can often be the CAP’s own laboratory accreditation program).
The Association of Molecular Pathology (AMP) concurs that tests with the highest risk to the patient most likely should meet some type of FDA oversight. However, AMP points out that assessing the risk of assays in the middle-and low-risk categories often varies with the particular clinical condition of the patient. Thus, AMP has concerns about the final regulatory requirements that the FDA might issue.
However, when it comes to Internet-based firms selling genetic tests marketed directly to consumers, most observers believe that FDA regulation of this class of laboratory-developed tests is a certainty.