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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test

InspectIR COVID-19 Breathalyzer identifies a chemical signature associated with SARS-CoV-2 in about three minutes with 91.2% sensitivity and 99.3% specificity

One company is hoping that it can make breathalyzers a viable, easier way to screen for SARS-CoV-2. It will soon have the opportunity to learn if consumers will accept this form of screening for COVID-19, as its device recently obtained an Emergency Use Authorization from the FDA.

On April 14, 2022, InspectIR Systems, LLC, of Frisco, Texas, was granted the US Food and Drug Administration’s first-ever emergency use authorization (EUA202006) for a portable breath test device designed to screen for SARS-CoV-2 infection. Clinical laboratories that perform COVID-19 testing will want to compare the high-level sensitivity of this breath test compared to rapid antigen tests currently used for COVID-19 screening.

The InspectIR COVID-19 Breathalyzer uses gas chromatography-mass spectrometry to identify mixtures of five volatile organic compounds (VOCs) uniquely associated with the disease, the FDA said in a news release announcing the EUA.

The device is about the size of a carry-on suitcase. It provides test results in less than three minutes and is currently authorized for use with subjects who are 18 or older.

The FDA’s EUA limits use of the device to “a qualified, trained operator under the supervision of a healthcare provider licensed or authorized by state law to prescribe tests,” the federal agency said. The test “can be performed in environments where the patient specimen is both collected and analyzed, such as doctor’s offices, hospitals, and mobile testing sites.”

Jeffrey Shuren, MD, JD
The InspectIR COVID-19 Breathalyzer device “is yet another example of the rapid innovation occurring with diagnostic tests for COVID-19,” said Jeffrey Shuren, MD, JD (above), director of the FDA’s Center for Devices and Radiological Health (CDRH), in the news release. A portable device that can identify SARS-CoV-2 infections in a few minutes with 91% specificity may be of great interest to clinical laboratory companies operating COVID-19 popup testing sites around the nation. (Photo copyright: US Food and Drug Administration.)

In granting the authorization, the FDA cited results of a study with 2,409 participants in which the test had sensitivity (correct positive results) of 91.2% and specificity (correct negative results) of 99.3%. “The test performed with similar sensitivity in a follow-up clinical study focused on the Omicron variant,” the agency stated.

“The FDA continues to support the development of novel COVID-19 tests with the goal of advancing technologies that can help address the current pandemic and better position the US for the next public health emergency,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health (CDRH), in the news release.

In its coverage of the EUA, CNET noted that the InspectIR breath test is more sensitive than rapid antigen tests but not as sensitive as PCR tests. The FDA advised that people who receive a positive test result with the InspectIR COVID-19 Breathalyzer should follow up with a PCR molecular test.

How the InspectIR COVID-19 Breathalyzer Works

InspectIR LLC was founded in 2017 by Tim Wing and John Redmond, Forbes reported. Their original goal was to develop a breathalyzer for detection of cannabis or opioid use. However, with the onset of the COVID-19 pandemic, the entrepreneurs decided to adapt the technology into a SARS-CoV-2 diagnostic test.

Lacking a background in chemistry, they turned to Guido Verbeck, PhD, head of the University of North Texas Laboratory of Imaging Mass Spectrometry (UNT-LIMS) in Denton, Texas, to help develop the breath test.

As described in the FDA’s EUA documents, a subject breathes into the device using a sterilized one-time-use straw. A pre-concentrator collects and concentrates the five targeted VOCs, all from the ketone and aldehyde families of organic compounds. These go to a Residual Gas Analyzer, and an algorithm determines whether the sample contains the chemical signature associated with a SARS-CoV-2 infection.

Redmond told Forbes that the specific mix of VOCs is proprietary. The article notes that Wing, Redmond, and Verbeck have patented the pre-concentrator technology.

The devices are manufactured at a Pfeiffer Vacuum Inc. facility in Indiana. The InspectIR founders told Forbes they expect to produce 100 units per week in a start-up phase with plans to ramp up as sales increase. They also plan to look at applications for other respiratory diseases.

InspectIR has not announced exact pricing, but Time reports that the company will lease the equipment to clients, and that pricing per test will be comparable to rapid antigen tests.

InspectIR’s first breathalyzer device is receiving much positive coverage from the media. Should it prove to effective at spotting COVID-19 at popup testing sites, it may supplant traditional clinical laboratory rapid antigen tests as the screening test of choice.   

Stephen Beale

Related Information:

Coronavirus (COVID-19) Update: FDA Authorizes First COVID-19 Diagnostic Test Using Breath Samples

The First COVID-19 Breathalyzer Test Is Coming to the US

Frisco Startup Gets FDA Approval on COVID Breathalyzer after Teaming Up with UNT Researcher

Meet the Founders of the $2.7 Million Startup Behind the New COVID Breathalyzer

FDA Authorizes First COVID-19 Breath Test

How a New Breath Test Could Make Mass COVID Testing Easier

FDA Authorizes First COVID-19 Breath Test Meet the InspectIR COVID-19 Breathalyzer Test Just Authorized by the FDA

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?

Pathologists and Researchers Predict Development Trajectory for Biomarker-based Molecular Diagnostics in Support of Translational Medicine

Emerging field of translational medicine expected to contribute to more informative studies that provide superior data for making medical decisions

These are boom times for translational medicine. That’s the term used to describe how the health of individuals and the community can be improved through applying new knowledge into diagnostic tools (including medical laboratory tests), medicines, procedures, policies, and education.

Rapid developments in the field of translational medicine include a role for pathologists who are discovering and validating molecular biomarkers associated with diseases.

Pathologists Have a Role in the Science of Translational Medicine

Translational medicine was the centerpiece in an interview conducted with an expert in biomedical research. Translational medicine is “where unproven observations advance to increasingly large and more informative studies to provide definitive and comparative information for a medical decision in routine clinical practice” contended Biomedical Consultant John Sninsky, Ph.D., former Vice President of Discovery Research at Alameda, California-based Celera Diagnostics. He was quoted in an interview published by GenomeWeb.

In validating translational medicine findings, Sninsky noted that everyone (e.g. pathologists, clinical laboratory scientists, and medical technologists) who contribute to the process must “weigh and balance” information so that it’s not used prematurely, but also not delayed when it has been proven useful to medical decisions. “So, in the end, no one piece of information, whether it be the conventional diagnostic test or the new test, will suffice for medical decisions, but will require gathering and reflecting on as much of the information as possible,” added Sninsky.

Large-scale Studies Better Sources for Personalized Medical Data

The goal of “personalized medicine” is for doctors to be able to prescribe treatments that more effectively “target” their patients’ unique physiologies and conditions. How to best conduct research and interpret the findings in ways that advance clinical care is under debate, as experts address the issues of individualized care versus population management.

What makes translational medicine relevant to pathologists, clinical chemists, and other clinical laboratory scientists is that this field of science is already changing how research studies and clinical trials are designed and conducted. Experts knowledgeable in this field predict that the principles of translational medicine will support important improvements.

First, these methods will be used to design clinical studies that are less expensive and faster to complete. Second, when such studies are conducted in this fashion, there will be a faster timeline between publication of findings and acceptance by providers, payers, and patients. Both improvements have the potential to directly benefit clinical labs as they develop new medical laboratory tests, conduct the clinical studies needed to demonstrate patient benefits, and then clear regulatory requirements needed to bring these new diagnostic assays to market.

The best method for gathering that data, however, is in question, noted Sninsky. He thinks large-scale studies are a better source for accumulating the needed data than research on individuals. “If you identify personalized medicine as information that’s truly unique to an individual, we actually think that information applicable to segments of the population will prove more timely and more important,” stated Sninsky, who then added, “we think that maybe calling it ‘targeted medicine’ rather than personalized medicine makes the case in point.”

Biomedical Consultant John Sninsky, Ph.D

Biomedical Consultant John Sninsky, Ph.D. (pictured above), former Vice President of Discovery Research at Alameda, California-based Celera Diagnostics, said in an interview with GenomeWeb that Targeted Medicine is more descriptive of where disease management is heading, rather than Personalized Medicine, because gathering information on a segment of the population is more straight forward than gathering information on an individual. (Photo copyright Celera Diagnostics)

Sninsky pointed out that validation and demonstration of utility only comes with replication in large studies. Therefore, in order to be effective, he suggested that applicable information would usually address about 10% of the population, “so disease management or health management, in the context of targeted medicine, is the way we think about it.”

Role of Clinical Laboratories in the Accelerated Development of In Vitro Diagnostic Assays

According to Sninsky, the natural progression and availability of diagnostics won’t change much. Large clinical reference laboratories will continue to create laboratory-developed assays. These “home-brews” will then evolve into FDA-approved in vitro diagnostic products that get distributed to “lower-throughput” clinical laboratories.

Sninsky further observed that sometimes these “smaller service laboratories” end up offering the assays as a [clinical] service after they’re launched. This accelerates the assay’s development as an in vitro product, he said, noting that the advantage of in vitro diagnostic products over services is their widespread availability.

NIH Support for Translational Medicine Steps Up FDA Regulatory Process

Sninsky acknowledged that getting biomarker-based molecular diagnostics validated and cleared through the Food and Drug Administration (FDA) and into the hands of physicians continues to be an onerous process. The FDA, however, has taken steps to accelerate the process, which Sninsky welcomes.

“One of the things I think is really good news is the stand that the U.S. regulatory agency has taken in terms of saying we’re going to help this process along,” he noted. “If someone would have said to me 15 years ago that the FDA was going to be leading the charge of the application of biomarkers, I would have been pessimistic about that.”

Since launching its Experiential Learning Program (ELP), the FDA’s Center for Devices and Radiological Health (CDRH) has accelerated the pre-market approval rate of medical and diagnostic devices, which includes in vitro diagnostic products.

Support for advancing the translational medicine approval process was demonstrated by the National Institutes of Health (NIH) in 2011 with the establishment of the National Center for Advancing Translational Sciences (NCATS). NIH also recently launched a Precision Medicine Initiative that aims to use genetic data from individuals to personalize diagnostic and therapeutic strategies. This $215 million project is pending Congressional approval of the President’s 2016 budget. (See Dark Daily, “Obama’s $215 Million Precision Medicine Initiative: Will Congress Fund It and Can It Advance Genetic Testing and the Value of Clinical Laboratory Services?”, March 23, 2015.)

Clinical Laboratories Provide the Diagnostic Tests for Physicians

While the clinical laboratories that run these tests do help in the development and wider distribution of in vitro diagnostic assays, Sninsky believes that caregivers, health plans, and patients have a greater role in demonstrating clinical effectiveness. “What our experience has been is it’s not the clinical labs who will decide whether new biomarkers are used, but instead will be the practicing clinicians, the reimbursement agencies, and the patients who see value in them that will make those decisions,” concluded Sninsky.

–Patricia Kirk

Related Information:

‘Targeted Medicine’: New Name of the Game 

Obama’s $215 Million Precision Medicine Initiative: Will Congress Fund It and Can It Advance Genetic Testing and the Value of Clinical Laboratory Services? 

Weill Cornell and New York Presbyterian to Create New Precision Medicine Institute to Use Genome Sequencing to Individualize Cancer Treatment 

FDA Pushes Forward with Plans to Regulate Laboratory-Developed Tests, in a Move that Will Impact Many Clinical Laboratory Companies and Pathology Groups 

FDA Approving Devices Faster 

FDA Presents Plans to Ensure the Reliability of Laboratory-Developed Diagnostic Tests 

NIH and FDA Join Forces to Advance Translational Medicine and Regulatory Science 

FDA Expands Its Internal Program to Learn More from Companies about Medical Device Manufacturing 

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