News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

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News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
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FDA Issues its First Emergency Use Authorization for an Antigen-based Diagnostic as Top IVD Manufacturers Race to Supply Medical Laboratories with COVID-19 Tests

Though experts say an antigen test is not as accurate as PCR tests, its low cost, ease of use, and widespread availability make it a boon for clinical labs performing COVID-19 testing

While COVID-19 exploded around the world, the US Food and Drug Administration (FDA) unleashed the nation’s in vitro diagnostics developers by issuing dozens of Emergency Use Authorizations for new coronavirus laboratory-developed tests (LDTs). Most of these EUAs are for Reverse Transcription-Polymerase Chain Reaction (RT-PCR) tests that detect the presence of SARS-CoV-2, the coronavirus that causes the COVID-19 illness, and for Enzyme-linked Immunosorbent Assay (ELISA) serological tests that detect antibodies present in the blood of people who have become infected with the coronavirus.

However, one LDT that received a lot of media attention was the Sofia 2 SARS Antigen FIA from Quidel (NASDAQ:QDEL), which received an EUA on May 8. The assay is designed to run on the company’s Sofia 2 Fluorescent Immunoassay Analyzer and is the first antigen test for which the FDA has issued an EUA.

As former FDA commissioner Scott Gottlieb, MD, explained on Face the Nation, “this kind of technology is a real game changer … it’s a very rapid test that could be used in a doctor’s office. Doctors now have about forty thousand of these Sofia machines already installed in their offices … you do a simple nasal swab and the test itself scans for the antigens that the virus produces.

“The test is about 85% sensitive. So, let’s say a hundred people come into a doctor’s office who have COVID-19, eighty-five of them are going to be able to be tested positive with this test very quickly. It’s a cheap test. It’ll probably be about five dollars a test and you can get a result within five minutes … you’re getting a very fast result and you can start to take action immediately.

“The company itself said that they’re going to be able to produce about two hundred thousand of these tests starting right away. But in several weeks, they’ll be able to produce up to 1.5 million a week. So, this dramatically expands our testing capacity as long as doctors are able to run these tests in their offices.”

Former FDA Commissioner Scott Gottlieb, MD
In an interview on CBS’ Face the Nation, former FDA Commissioner Scott Gottlieb, MD (above), said, “These antigen-based tests aren’t as reliable, meaning they’re not as sensitive. So, they’re going to miss some patients who have COVID. But in the hands of a doctor who already has a high index of suspicion that the patient may have the disease … they allow you to dramatically expand testing. And they’re very cheap. They’re very easy to perform. And again, most doctors have these machines already in their offices.” (Photo copyright: US Food and Drug Administration.)

Other LDTs That Have Received EUAs

Here’s a look at other laboratory-developed tests from major manufacturers that have received emergency-use authorizations from the FDA:

Abbott Laboratories

Test: Abbott RealTime SARS-CoV-2 assay
Type: Molecular (rRT-PCR)
EUA Issued: March 18, 2020

This test is designed for use with Abbott’s m2000 RealTime system, which is installed in about 200 US medical laboratories, the company says. It can run up to 470 patient samples in 24 hours. As of a May 11 statement, the company said it had shipped more than two million tests in the US.

Test: Alinity m SARS-CoV-2 assay
Type: Molecular (rRT-PCR)
EUA Issued: May 11, 2020

This test is designed for use with Abbott’s Alinity m system, which the company describes as its “most advanced laboratory molecular instrument,” with the ability to run up to 1,080 tests in 24 hours, according to a press release.

Type: Molecular
Instrument: ID Now
EUA Issued: March 27, 2020

This is a rapid test designed for use with the ID Now system, a compact portable instrument for point-of-care settings such as urgent care clinics. As of May 11, Abbott said it had shipped more than 1.7 million tests in the US, and that it planned to increase manufacturing capacity to two million tests per month.

However, the test has encountered some stumbling blocks. On May 14, the FDA issued an alert stating that the ID Now COVID-19 test could produce inaccurate negative results. This came after researchers at NYU Langone Health, Northwell Health, and Cleveland Clinic reported problems with the test, according to MedTech Dive. Abbott issued a statement suggesting that the problems were due to improper sample collection and handling, however, the FDA said that Abbott had agreed to conduct post-market studies to identify the cause of the false negatives and suggest remedial actions.

Test: SARS-CoV-2 IgG assay
Type: Chemiluminescent microparticle immunoassay (CMIA) antibody test
EUA Issued: April 26, 2020

This is a qualitative test designed to detect the presence of IgG antibodies following a SARS-CoV-2 infection. The FDA authorized use of the assay on Abbott’s Architect i2000SR system in April, and then followed up with a May 11 EUA for its use on the Alinity i system. In a statement, Abbott said it planned to ship 30 million tests globally starting in May.


Test: Xpert Xpress SARS-CoV-2
Type: Molecular (rRT-PCR)
EUA Issued: March 21, 2020

In a March statement, the FDA touted this as the first point-of-care COVID-19 test to receive an EUA. The company estimates the detection time as approximately 45 minutes. It is designed for use with Cepheid’s GeneXpert Dx diagnostic software and GeneXpert Infinity systems, which have nearly 5,000 US installations, according to a Cepheid statement.

Hologic, Inc.

Test: Aptima SARS-CoV-2 assay
Type: Molecular (Dual Kinetic Assay)
EUA Issued: May 14, 2020

This test runs on Hologic’s Panther system, which, according to a Hologic press release, can provide results in about three hours and run more than 1,000 tests per day. The company claims that more than 1,000 Panther systems are installed in US labs, and that it expects to produce an average of one million tests per week.

This was the second Hologic test to receive and EUA. On March 16, the FDA issued an EUA for the Panther Fusion SARS-CoV-2 assay, a PCR test that runs on the Panther Fusion system.

Ortho Clinical Diagnostics

Test: VITROS Total and IgG COVID-19 Antibody Test
Type: ELISA Antibody Test
EUA Issued: April 14, 2020

Ortho’s antibody test is designed for use with its VITROS XT 7600, 3600, 5600, and ECi/ECiQ immunodiagnostic systems, which, the company says are installed in more than 1,000 US labs. The Total Reagent Pack is a qualitative test that detects the presence of all antibodies against SARS-CoV-2.

On April 24, Ortho announced it had received another FDA EUA, this one for its Anti-SARS-CoV-2 IgG test, which detects the presence of IgG antibodies. In a statement, the company said it expects to produce “several million” IgG tests per month.

Roche Diagnostics

Test: cobas SARS-CoV-2
Type: Molecular (rRT-PCR)
EUA Issued: March 12, 2020

This test is designed for use with Roche’s cobas 6800 and 8800 systems. The 6800 can process up to 384 results in an eight-hour shift, Roche says, compared with 1,056 results for the 8800 model. The company says results are available in about 3.5 hours. In a statement, Roche said it planned to ship 400,000 tests per week.

Test: Elecsys Anti-SARS-CoV-2
Type: Electrochemiluminescence immunoassay (ECLIA) Antibody Test
EUA Issued: May 2, 2020

Roche describes this as a qualitative antibody test that can be used on cobas e series immunoassay analyzers. Testing time is 18 minutes. As of May 19, the test was live at more than 20 US labs, “with plans in the next several weeks to increase to more than 200 commercial and hospital lab sites with the ability to perform millions of tests per week,” the company stated in a press release.

It’s likely the FDA will continue to issue emergency-use authorizations as the agency receives more applications from IVD manufacturers.

—Stephen Beale

Related Information:

FDA Approves First Antigen Test for Detecting the Coronavirus

Ex-FDA Chief Calls New Covid-19 Antigen Test a ‘Game-Changer’

Serology-based Tests for COVID-19

Serology Testing Free Webinar

Molecular-based Tests for COVID-19

Current Molecular and Antigen Tests with FDA EUA Status

FDA Emergency Use Authorization (EUA) Information, and List of All Current EUAs

Canadian Scientists and Medical Researchers Urge Health Canada to Regulate Laboratory-developed Tests

Lack of regulations and quality management jeopardizes the quality and safety of LDTs, claim experts in clinical laboratory medicine in a commentary to Canadian policymakers

Health Canada is the latest government healthcare organization under pressure to enact legislation that regulates laboratory-developed tests (LDTs). In a public commentary, several members of the Institute of Health Policy, Management and Evaluation (IHPME) at the University of Toronto in Ontario, urged Canadian lawmakers to follow the European Union’s lead and find ways to monitor LDTs in Canada.

The IHPME members published their comments in the Canadian Medical Association Journal (CMAJ), a peer-reviewed journal owned by Joule Inc., a subsidiary of the Canadian Medical Association. In it, they claim “recent expansion of the molecular diagnostics industry has revealed weaknesses in Canada’s regulatory system for laboratory-developed tests, which are not subject to statutory regulations on medical devices.”

For pathologists and clinical laboratory professionals in both Canada and the United States, these recent actions show the concerns many experts have as they watch the explosive growth in the use of laboratory-developed tests in both countries. In many ways, the swift advances in molecular and genetic diagnostics is outrunning the ability of government regulators to keep pace with use of LDTs in clinical care settings.

In their commentary in CMAJ, the IHPME members also claim the review and evaluation of LDTs in Canada is inconsistent. Some LDTs they say, may endure stringent assessments and have endorsements by clinical guidelines or findings that are published in scientific journals. Other LDTs, however, may have no analysis at all.

In addition, the IHPME members point out that there is no national registry kept of LDTs. They theorize that a lack of proper regulation, controls, and quality management “has potentially jeopardized the delivery of quality, safe, timely, and appropriate care.”

The researchers calling on Health Canada to address these issues include:

  • Kelly Holloway, PhD, Research scientist at University of Toronto;
  • Fiona A. Miller, PhD, Professor of Health Policy and IHPME Chair in Health Management Strategies;
  • François Rousseau, PhD, Professor, Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Quebec;
  • Alberto Gutierrez, PhD, Partner, NDA Partners LLC, former Director, Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health (CDRH);
  • Stuart Hogarth, PhD, Lecturer in Sociology of Science and Technology, University of Cambridge, Cambridge, UK.
During an exclusive presentation offered by The Dark Report (Dark Daily’s sister publication) in 2015, Alberto Gutierrez, PhD (above), who at that time was Director, Office of In Vitro Diagnostics and Radiological Health at the FDA, said, “LDTs are an area that will be difficult to regulate. There is a broad set of tests. Some of the LDTs are very good. Some of them require a lot of expertise from the pathologists and some of them don’t. Regulating LDTs in a way that makes sense and that does not disrupt what’s going on [in clinical laboratories] is going to be difficult.” (Photo copyright: FDA.)

Canadian Scientists Call on Health Canada to Take the Lead on Regulating LDTs

In the US, the FDA has been making moves to regulate LDTs since 2010, with much opposition from clinical laboratories and In Vitro Diagnostic (IVD) manufacturers. The FDA describes LDTs as internally designed clinical laboratory tests that are developed, manufactured, and used within a single laboratory. They have not undergone government regulatory review, can be simple or complex, and can be utilized to detect a variety of analytes.

Health Canada is the name of a department that falls under the purview of the Minister of Health and is part of Canada’s Health Portfolio. It is responsible for helping Canadians maintain and improve their health. Other agencies included in the Health Portfolio are:

According to the IHPME paper, however, Health Canada currently does not have a way to regulate LDTs, and no government agency in that country is responsible for the oversight of laboratory-developed tests. Only LDTs that are marketed as test kits are evaluated and reviewed by Health Canada. 

“The current laboratory regulatory system in Canada involves a mixture of public and private entities and operates with oversight from provincial governments, nongovernmental organizations, and professional societies,” the IHPME paper states, adding, “most provinces and territories rely on voluntary standards that are unevenly applied, with little auditing and systematic testing to ensure quality.”

The authors also note that the current lab regulations in Canada apply only to the operations of the medical laboratories themselves, encompassing such things as lab environments, personnel, accreditation, and quality control. They believe the loophole regarding LDTs needs to be addressed, and they urged Health Canada to “demonstrate leadership” by subjecting these tests to regulations that are currently applied to medical devices and pharmaceuticals.

Other Countries Regulate LDTs, though Not Without Controversy

In support of their call to action, IHPME researchers noted that Australia, the EU, and the US all have taken steps to regulate LDTs.

The Australian government began oversight of LDTs in 2010 by subjecting high-risk LDTs to external evaluation and then tracking them in a public registry.

An EU regulation, which was passed in 2017, will administer regulatory review of LDTs manufactured on an industrial scale, which targets commercial laboratories. The law exempts LDTs utilized within individual hospital laboratories and should be fully implemented by 2022.

Though on its radar since the 1990s, in 2010, the FDA officially announced its intent to regulate LDTs in the US. The agency released an initial draft approach for doing so starting in 2014, held a public workshop on the topic in 2015, and released a discussion paper in 2017. At this time, however, the FDA is not regulating LDTs, though the agency remains open to the possibility.

Dark Daily has reported extensively over the years on the development of LDTs and the controversy surrounding the FDA’s moves to regulate them.

According to the FDA website, problems with several high-risk LDTs have been identified, including:

  • Claims that are not adequately supported with evidence;
  • Lack of appropriate controls which may yield erroneous results; and
  • Falsification of data.

However, in “FDA Looks to Clamp Down on Laboratory-Developed Tests and Put an End to ‘Wild West of Medicine’: Might CLIA Problems at Theranos Support FDA’s Position?Dark Daily, May 4, 2016, Roger D. Klein, MD, JD, Chair of the Association for Molecular Pathology (AMP) Public Relations Committee, and Medical Director, Molecular Oncology at Cleveland Clinic, called a report released by the FDA in 2015 “mostly a hodgepodge of outlier assays.”

The FDA’s report, titled, “The Public Health Evidence for FDA Oversight of Laboratory Developed Tests,” reviewed 20 case studies of LDTs for Lyme disease, ovarian cancer, whooping cough, fibromyalgia, prostate cancer, autism, breast cancer, melanoma, Vitamin D, and other conditions. The agency concluded that in many instances “patients have been demonstrably harmed or may have been harmed by tests that did not meet FDA requirements.”

Klein noted, however, that “The 20 tests described by FDA are mostly a hodgepodge of outlier assays including tests that were never offered, tests for which comparable FDA assays perform poorly, tests for poorly defined disorders with psychologic components, and use of an FDA-approved test off-label.” He continued, “That FDA could find only these dubious examples out of the many thousands of laboratory-developed procedures (LDPs) that benefit patients each day, calls into question the agency’s rationale for expanding its regulatory scope to include LDPs.”

Perhaps this is why the FDA has yet to implement regulations for LDTs. The controversy continues.

Whether Health Canada will accept the advice of the IHPME scientists and take steps to regulate laboratory-developed tests in Canada remains to be seen. As more LDTs are created and manufactured, however, it is probable that governments will continue to evaluate the administration and oversight of laboratory-developed tests.

In both Canada and the United States, pathologists, clinical laboratory managers, and executives at in vitro diagnostic manufacturers can expect an ongoing tug-of-war between government regulators and the lab industry over the most appropriate ways to regulate LDTs.

—JP Schlingman

Related Information:

Health Canada Needs to Act on Laboratory-developed Diagnostics

Laboratory Developed Tests

The Public Health Evidence for FDA Oversight of Laboratory Developed Tests: 20 Case Studies

Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)

FDA Discussion Paper on Laboratory Developed Tests

FDA Announces Intention to Regulate LDTs as Devices

FDA Official Makes Case in Favor of LDT Guidance

Regulation of Laboratory Developed Tests by FDA: Time for the Agency to Cease and Desist Until Congress Enacts Legislation

Johns Hopkins University Study Finds Laboratory-Developed Liquid Biopsy Tests Can Give Different Results; Call for ‘Improved Certification’ of Medical Laboratories That Develop These LDTs

FDA Looks to Clamp Down on Laboratory-Developed Tests and Put an End to ‘Wild West of Medicine’: Might CLIA Problems at Theranos Support FDA’s Position?

Biomarker Trends Are Auspicious for Pathologists and Clinical Laboratories

Few anatomical tools hold more potential to revolutionize the science of diagnostics than biomarkers, and pathologists and medical laboratories will be first in line to put these powerful tools to use helping patients with chronic diseases

There’s good news for both anatomic pathology laboratories and medical laboratories worldwide. Large numbers of clinically-useful new biomarkers continue to be validated and are in development for use in diagnostic tests and therapeutic drugs.

Clinical laboratories rely on biomarkers for pathology tests and procedures that track and identify infections and disease during the diagnostic process. Thus, trends that highlight the critical role biomarkers play in medical research are particularly relevant to pathology groups and medical laboratories.

Here’s an overview of critical trends in biomarker research and development that promise to improve diagnosis and treatment of chronic disease.

Emerging Use of Predictive Biomarkers in Precision Medicine

Recent advances in whole genome sequencing are aiding the development of highly accurate diagnostics and treatment plans that involve the development and use of Predictive Biomarkers that improve Precision Medicine (PM).

PM involves an approach to healthcare that is fine-tuned to each patient’s unique condition and physiology. As opposed to the conventional one-size-fits-all approach, which looks at the best options for the average person without examining variations in individual patients.

Predictive biomarkers identify individuals who will most likely respond either favorably or unfavorably to a drug or course of treatment. This improves a patient’s chance to receive benefit or avoid harm and goes to the root of Precision Medicine. (Image copyright: Pennside Partners.)

The National Institutes of Health (NIH) defines PM as “an emerging approach for disease treatment and prevention that considers individual variability in genes, environment, and lifestyle for each person.” It gives physicians and researchers the ability to more accurately forecast which prevention tactics and treatments will be optimal for certain patients.

Combining Drugs for Specific Outcomes

Cancer treatment will be complimented by the utilization of combination drugs that include two or more active pharmaceutical ingredients. Many drug trials are currently being performed to determine which combination of drugs will be the most favorable for specific cancers.

Combination drugs should become crucial in the treatment of different cancers treatments, such as immunotherapy, which involves treating disease by inducing, enhancing, or suppressing an immune response.

Biomarkers associated with certain cancers may enable physicians and researchers to determine which combination drugs will work best for each individual patient.

Developing More Effective Diagnostics

In Vitro diagnostics (IVDs) are poised for massive growth in market share. A report by Allied Market Research, states the worldwide IVD market will reach $81.3 billion by 2022. It noted that IVD techniques in which bodily fluids, such as blood, urine, stool, and sputum are tested to detect disease, conditions, and infections include important technologies such as:

Allied Market Research expects growth of the IVD market to result from these factors:

  • Increases in chronic and infectious diseases;
  • An aging population;
  • Growing knowledge of rare diseases; and
  • Increasing use of personalized medicines.

The capability to sequence the human genome is further adding to improvements in diagnostic development. Pharmaceutical companies can generate diagnostic counterparts alongside related drugs.

Biopsies from Fluid Sources

Millions of dollars have been spent on developing liquid biopsies that detect cancer from simple blood draws. The National Cancer Institute Dictionary of Cancer Terms defines a liquid biopsy as “a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood.”

At present, liquid biopsies are typically used only in the treatment and monitoring of cancers already diagnosed. Companies such as Grail, a spinoff of Illumina, and Guardant Health are striving to develop ways to make liquid biopsies a crucial part of cancer detection in the early stages, increasing long-term survival rates.

“The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage,” said Dr. Richard Klausner, Senior Vice President and Chief Medical Officer at Grail.

Grail hopes to market a pan-cancer screening test that will measure circulating nucleic acids in the blood to detect the presence of cancer in patients who are experiencing no symptoms of the disease.

Clinical Trials and Precision Medicine

The Precision Medicine Initiative (PMI), launched by the federal government in 2015, investigates ways to create tailor-made treatments and prevention strategies for patients based on their distinctive attributes.

Two ongoing studies involved in PMI research are MATCH and TAPUR:

  1. MATCH (Molecular Analysis for Therapy Choice) is a clinical trial run by The National Cancer Institute. The researchers are studying tumors to learn if they possess gene abnormalities that are treatable by known drugs.
  2. TAPUR (Targeted Agent and Profiling Utilization Registry), is a non-randomized clinical trial being conducted by the American Society of Clinical Oncology (ASCO). The researchers are chronicling the safety and efficacy of available cancer drugs currently on the market.

New Tools for Pathologists and Clinical Laboratories

The attention and funds given to these types of projects expand the possibilities of being able to develop targeted therapies and treatments for patients. Such technological advancements could someday enable physicians to view and treat cancer as a product of specific gene mutations and not just a disease.

These trends will be crucial and favorable for clinical laboratories in the future. As tests and treatments become unique to individual patients, pathologists and clinical laboratories will be on the frontlines of providing advanced services to healthcare professionals.

—JP Schlingman

Related Information:

5 Trends Being Impacted by Biomarkers

Immuno-Oncology Stories of 2016

Bristol-Myers Leads Immune-Oncology Race but Merck, Astrazeneca and Roche Still Have Contenders

Five Companies to Watch in the Liquid Biopsy Field

Illumina Spinoff GRAIL to Trial Liquid Biopsies for Early Detection of Cancer

Illumina Forms New Company to Enable Early Cancer Detection via Blood-Based Screening

A to Z List of Cancer Drugs

Personalized Medicine and the Role of Predictive vs. Prognostic Markers

Understanding Prognostic versus Predictive Biomarkers

NCI-MATCH Trial (Molecular Analysis for Therapy Choice)

Six Months of Progress on the Precision Medicine Initiative

Home-testing IVD Diagnostic Devices Win Rigorous MDEA Design Awards as Part of Ongoing Trend to Move Medical Laboratory Tests Closer to Patient

Innovative designs promote in vitro home-testing medical diagnostic devices that could impact the work done in clinical laboratories

With greater frequency, new diagnostic technologies make it possible to move medical laboratory tests out of the traditional central lab facility and closer to the patient—including patient home self-testing. Even as this happens, engineers and designers are delivering elegant, well-designed devices designed for use in clinical laboratories as well as in near-patient settings.

Evidence of this trend comes from the most recent winners in the annual contest known as the Medical Device Excellence Awards (MDEA). In this year’s contest, two of the products receiving awards were medical laboratory test devices that were deemed to be innovative solutions to improve the lab testing process.

This contest intends to “recognize significant advances in medical product design and engineering that improve the quality of healthcare delivery and accessibility.” The competition was first held in 1998 and is sometimes described as the “Oscars” of the medical device. Receiving an MDEA medal offers validation, publicity, and a host of other benefits. (more…)