Lab-developed tests were controversial before the COVID-19 pandemic, and there was attempts at regulating them more in the United States.  Then came a massive infectious disease threat for which lab developed tests were essential.  The sudden onset of a disease for which there were no existing test products, so labs had to develop their own.

Lab-developed tests are likely to be a fifth of tests, according to a recent survey by the Association for Molecular Pathology.

There has been a running stalemate under the role of laboratory-developed tests, which may or may not change in the wake of COVID-19.  Originally, LDTs were designed to be solutions that do not otherwise exist yet on the market. Hence, FDA has not enforced premarket reviews of LDTs. Instead , LDTs are regulated by the Centers for Medicare and Medicaid Services (CMS), where they are categorized as high- complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). However, technology advancements have facilitated designing of complex LDTs, with some being similar to IVD tests that have undergone FDA review before entering the market.

The majority of LDTs are based on molecular diagnostic technologies such as nucleic acid amplification, array-based hybridization, NGS, and liquid biopsies.

Could COVID-19 break the stalemate towards the side of test innovation and LDT?  Lab Developed Tests were critical for the crisis in late march. For instance there were media reports  January that SARS-CoV-2 virus had reached the US, lab professionals said they were hesitant to launch LDTs. They were unsure if the agency would practice “enforcement discretion.”

One showdown proved ill-timed for the side of stricter FDA regulation of tests.   In March 2020, lawmakers introduced a bill that would vastly change the oversight system for diagnostics in this country and give the US Food and Drug Administration explicit authority to regulate tests developed by labs, legislators and media were confused by what seemed to be a reversal of need for more testing.    The bipartisan (VALID) Act was designed to streamline regulations and speed access to tests in public health emergencies like the present COVID-19 pandemic.

  Opponents argued that in the hands of the FDA, the lab industry would be overburdened with regulation and no longer nimble in the face of advancing science or a sudden public health crisis.

Kalorama Information produces 30 reports a year.  Their reports can be found at www.kaloramainformation.com

The landscape of COVID-19 testing has been rapidly evolving.  New products and services are continually being introduced, and regulatory approvals have been growing and expanding to include more types of tests, samples, and sample collection methods.  With the sudden global demand and governments loosening requirements during the crisis, there has been an unprecedented flood of products.  It has attracted scores of companies, some of which have rushed or cut corners and produced tests with low accuracy.  In many cases there have been recalls and the FDA has issued warning letters, revoked EUAs, and tightened some of its more lenient regulations, for example for Policy D antibody tests.

Along with labs procuring additional systems and increasing their staffing, there are other ongoing activities that are being undertaken to address the various challenges of COVID-19 testing.  The growth is expected to continue, even with some areas seeing declining cases for example in the US.  Most labs are using multiple suppliers’ COVID tests, as a way to hedge against shortages or other problems.

A significant but decreasing portion of countries still remains relatively unscathed with small numbers of cases.  There are only about 40 countries with zero to one case per day, out of 210, mainly islands or less-travelled areas.  Regions that are seeing their first spike in cases are now facing the issue of scaling up to the necessary volume.  Due to the unknowns that remain about the virus, it is also still a challenge to determine the appropriate level of testing.  Some lessons can be applied from the countries that were hit earlier

This is partly dictated by the existing instrumentation but there is usually some flexibility.  Pooling and other techniques are being incorporated to stretch supplies out for more tests.

Due to the supply situation as well as the nature of scientific collaboration, many professional organizations have taken the initiative to address the challenges.  The Association for Molecular Pathology (AMP), for example, has developed five key recommendations for testing labs to best respond to the pandemic, based on its recent survey –

 

  • Reassess type and location of SARS-CoV-2 testing services needed – better match to the situation
  • Reprioritize supply allocations based on clinical testing needs, which could change over time – e.g. as prevalence falls or climbs
  • Increase transparency, communication, and real-time transmission of information between laboratories and suppliers (commercial manufacturers and government) – reagent, supply, resource availability and supply quantities, allocation strategies etc
  • Real-time coordination amongst laboratories to leverage moments of excess capacity – share supplies to ensure rapid processing of samples
  • Standardize agency reporting format and processes for reportable infectious diseases during a pandemic – reduce significant burden on labs, reduce delays, establish electronic systems and formats.


For countries that are still at the beginning of the crisis, taking these steps could improve the chances of success; and for the others, they will likely be among the key considerations to prepare for the next pandemic.

Companion diagnostics are rising to the forefront of pharmaceutical development and treatment. Companion diagnostics increase the probability of clinical success by identifying patients with the presence of biomarkers or disease-specific therapeutic targets that can dramatically improve outcomes. The COVID-19 pandemic has gripped the world and continues to be a major area of research and development for diagnostic test developers.

Several approaches continue to evolve, including the use of personalized medicine technologies being adjusted to address the COVID-19 need.

Spartan Bioscience developed its CE and FDA approved DNA analyzer to detect risk of poor treatment choices for patients taking various antiplatelets, antidepressants and PPIs.  People carrying CYP2C19 mutations can impair drug metabolism and alter response to drug therapy.  Over the first-half of 2020, Spartan Bioscience has shifted its technology to focus on detecting COVID-19 and Legionella using its qPCR on-site DNA analyzer.

Our report on companion diagnostics (https://kaloramainformation.com/product/companion-diagnostics-in-the-covid-19-era/), and found that COVID-19 has had a small impact on the market for important cancer test and drug combinations.  But since the oncology therapeutics these tests help facilitate are critically important for patients, that impact was limited.  This was according to informal surveys of companion diagnostic vendors conducted by the authoring analysts of the market report.

Along with new developments, diagnostic service providers are also shifting workloads to address the demand for COVID-19 services.  MiraDx, for example, has opened its CLIA-certified lab to providing COVID-19 test services.  The lab has an analyze capacity of over 9,000 tests with no backlog, reported by MiraDx.  The company also reports test results are available in approximately 48 hours and are being prioritized for hospitals, essential workers and field-based healthcare workers.  MiraDx lists the test at $150 per completed test.
Minimal Ongoing Disruptions

Analysts contacted some oncology treatment centers and others focusing on CDx activity to determine the impact of COVID-19 on laboratory activity.  The analysts of the report found.

• Initial (March 2020) decline in CDx requisitions, yet by April 2020 this was largely resolved;
• Less than 10 percent reduction in test volume reported;
• Budgets largely frozen, no capital expenditures will be initiated in the foreseeable future;
• Some backlog on processing tests due to restructuring of hours and laboratory layout requirements; and
• By appointment only lab draws were in effect beginning around February 2020 for some facilities and ongoing through April 2020 which impacted test volume slightly.

Delaying treatment in patients with overall good prognosis would be detrimental to the outcome in some patients prescribed targeted therapies, primarily cancer therapies.  Therefore, oncologists report only minimal delays in treatment which is often determined case-by-case, dependent on factors such as disease status, cancer type, age of the patients, etc.

For example, systemic therapy may be delayed for a short period in patients aged 50 or older with non-aggressive tumor types; in contrast, delaying treatment in an aggressive tumor could be catastrophic to the patient’s outcome.  The National Institutes of Health (NIH) lists more than 200 clinical trials currently underway for COVID-19 biomarker discovery, development and clinical application.

Along with new developments, diagnostic service providers are also shifting workloads to address the demand for COVID-19 services.  MiraDx, for example, has opened its CLIA-certified lab to providing COVID-19 test services.  The lab has an analyze capacity of over 9,000 tests with no backlog, reported by MiraDx.  The company also reports test results are available in approximately 48 hours and are being prioritized for hospitals, essential workers and field-based healthcare workers.  MiraDx lists the test at $150 per completed test.

There is also a growing trend for treatment centers, specifically cancer treatment centers, and research hospitals to get involved in the COVID-19 recovery plan.  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University (Baltimore, Maryland, United States) is gearing up to commence a Phase II trial to promote recovery from COVID-19 with ivermectin or bicalutamide endocrine therapy.  The study is an interventional trial with an estimated enrollment of 60 participants that have had a confirmed PCR test of COVID-19 infection and require inpatient hospitalization due to COVID-19 with minimal or no respiratory symptoms. Estimated start date is June 2020 with estimated completion in June 2021.

 

In Kalorama Information’s Emerging Infections Testing report (https://kaloramainformation.com/product/emerging-infectious-disease-diagnostics-markets-and-trends/) , we discussed Chagas.  Chagas disease is named after the Brazilian physician Carlos Ribeiro Justiniano Chagas, who discovered the disease in 1909. Chagas disease (Trypanosoma cruzi, known as kissing bugs) is also referred to as American trypanosomiasis. It is endemic throughout Mexico, and Central and South America, and is caused by the protozoan parasite T cruzi, which is transmitted to humans by blood-sucking insects of the family Reduviidae (Triatominae).  Now there is word  that the Defense Department is concerned enough to embark on a study, which is just the latest indication of the disease threat in the United States.

Chagas disease is part of the trypanosomal group of diseases that includes human African trypanosomiasis (also known as African sleeping sickness), and leishmaniasis. These diseases are grouped together because they share a common family of vectors: African trypanosomiasis (Sleeping Sickness, caused by Trypanosoma brucei), South American trypanosomiasis (Chagas Disease, caused by Trypanosoma cruzi), and leishmaniasis (a set of trypanosomal diseases caused by various species of Leishmania).

Chagas represents one of the greatest and least publicized public health problems in Latin America. Transmission occurs through insects that spread in low-income rural and peri-urban housing and through uncontrolled blood transfusions.

Although mainly a vector-borne disease, Chagas disease can be acquired by humans through blood transfusions and organ transplantation, congenitally (from a pregnant woman to her baby), and through oral contamination (foodborne).

Chembio, Bioconcept and Altona Diagnostics are among the companies that produce tests for Chagas.   Last year, a study found that a combination of marketed rapid point-of-care (POC) diagnostics was useful in screening for Chagas disease in a study conducted in Bolivia. The results compared well with the gold standard enzyme-linked immunosorbent assay (ELISA) approach, which is a challenge in low-resource settings, researchers reported on December 19 in PLOS Neglected Tropical Diseases.  Molecular testing is the most effective technique, however it is not widely available for screening programs. There is some expectation that current advancements in miniaturization may lead to cost-effective molecular devices. In the meantime major health organizations have been motivated to take action.

Doctors in the United States that treat people with Chagas disease, a parasitic illness transmitted by the “kissing bug” in the Americas, are increasingly worried about the estimated 30,000 to 45,000 people that are at increased risk of complications from COVID-19 because they have Chagas-related heart problems. As an indication of that concern, the U.S. Department of Defense has granted 700,000 to Texas State University to conduct a study assessing the threat of Chagas disease to military bases. https://www.sanmarcosrecord.com/news/texas-state-university-study-chagas-disease-threat-military.

 

The fast spread of COVID-19, a respiratory condition, has healthcare systems focused on other diseases that could spread using the same method.  Kalorama Information’s Emerging Infectious Disease Diagnostics report: (https://kaloramainformation.com/product/emerging-infectious-disease-diagnostics-markets-and-trends/) details multiple types of viruses that are being tracked worldwide, many that have jumped from developing nations to developed ones.  These are some of the known infectious disease threats, and there is the possibility there could be unknown pathogens as well.

Streptococcus pyogenes (group A streptococcus, GAS) colonizes the throat or skin and is responsible for a broad spectrum of diseases that range from simple and uncomplicated pharyngitis and skin infections (impetigo, erysipelas, and cellulitis) to scarlet fever and life-threatening invasive illnesses including pneumonia, bacteremia, necrotizing fasciitis, streptococcal toxic shock syndrome (TSS), and sequelae such as acute rheumatic fever, reactive arthritis and glomerulonephritis.

Chlamydia pneumoniae [unrelated to the sexually transmitted disease] can trigger pulmonary infections.  Prevalence in the general population is high, reaching up to 70%.  Asymptomatic progression of an infection with Chlamydia pneumonia is often problematic because a primary infection may not be diagnosed until it has led to chronic conditions like asthma or chronic obstructive pulmonary disease.

Acute pharyngitis or Strep throat is one of the most frequent illnesses for which pediatricians and other primary care physicians are consulted, with an estimated 15 million visits per year in the United States.

Respiratory syncytial virus (RSV), which causes infection of the lungs and breathing passages, is a major cause of respiratory illness in young children.

“These are some of the known respiratory system-based infectious disease threats, and there is the possibility there could be unknown pathogens as well.”

Bordetella pertussis is the microorganism that causes the whooping cough; a very contagious infectious disease worldwide spread that affects mainly children aged 0 to 4.  Whooping cough was once a terrible menace to children, with hundreds of thousands of cases reported annually.  Then a vaccine drove cases down, and the illness became thought of as rare and even antiquated.  But it never totally disappeared; in 2018 the World Health Organisation reported 151,074 pertussis cases globally.  Based on 2008 data the WHO estimated that there were 89,000 deaths.

Discovered in 2001, human metapneumovirus (HMPV) shares many symptoms with the flu.  Research has shown that HMPV is one of the most common causes of acute respiratory infections.  For otherwise healthy children and adults, it tends to be a minor illness, but can be serious for populations including the very young, the very old and people with underlying health problems, such as asthma or chronic heart disease.

Besides respiratory conditions, diarrheal disease, also known as gastroenteritis (GI), affects approximately 1.7 billion people each year and is a leading cause of child morbidity and mortality worldwide and especially in developing countries. In the United States alone, 99 million cases of GI infection occur annually, leading to over 250,000 hospitalizations and 17,000 deaths.  Shiga toxin-producing E. coli are commonly associated with food- and water-borne outbreaks of diarrheal illness.  E. coli O157 is the most well-known strain and has been responsible for numerous outbreaks.

These diseases and others are a continued focus of development for in vitro diagnostic manufacturers.

Science and Medicine Group Inc. including Kalorama Information, SDi, BioInformatics, and IMV are marshaling our information and data resources to help those on the frontline in the fight against the COVID-19 virus. Science and Medicine Group Inc. is a market research and media company serving the life science, analytical instrument, diagnostic, medical imaging and dental industries. We also maintain four vibrant communities of more than 300,000 scientists and medical professionals including LabPulse.com, AuntMinnie.com, DrBicuspid.com, and The Science Advisory Board

Today we gave access to our Knowledge Center to employees of the Centers for Disease Control (CDC).   The Knowledge Center is an innovative information sharing platform that enables users to search almost 1,000 detailed reports on a wide variety of diagnostic and medical imaging technologies to understand the science behind the technologies as well as the capabilities and strategies of the market’s supplier base. The CDC will be able to use all the clinical diagnostics from Kalorama and diagnostic imaging from IMV to better coordinate a response among market participants from CT, Ultrasound, Molecular, and Point-of-Care diagnostics. We believe an “all diagnostics on deck” approach to COVID-19 detection would greatly accelerate the detection and also ease the strain on laboratory testing, some of which requires extensive PPE and often has time delays between sample collection and insight.

Kalorama Information, the most trusted name in healthcare and clinical diagnostics market research, has put a large database of diagnostic instruments in the U.S. online free of charge to start-ups, commercial entities developing COVID-19 solutions, and hospitals laboratories so they can locate sites that do testing in the US market. The entire Clinical Masterfile details the manufacturer and model of 39,628 clinical diagnostic instruments at 5,331 U.S. hospitals. Today we are making the COVID-19 instrument part of our Kalorama Clinical Masterfile available for commercial suppliers and local hospitals and labs.  These data will allow national and local hospitals and suppliers to find each other and get the necessary COVID-19 kits, reagents, and controls distributed through national supply chains or local swaps. The list has 1,787 FDA-EUA Approved Instruments or Instruments that can run EUA COVID-19 TaqMan ™ Assays.  We are also releasing 157 Instruments that are COVID-19 capable with Staff Training and Adjustment for Lab Developed Tests. Laboratory professions will be able to use the database to find each other and share reagents and kits needed to maintain their labs’ testing volume.

Bruce Carlson, Publisher of Kalorama Information said, “Market knowledge is essential for developers, potential investors and government agencies.  A crisis brings attention to many markets previously unconsidered, and new employees and agencies need to stay informed with foundational knowledge.  Market research exists for this purpose. Kalorama, IMV and other Science and Medicine Group Publications have available market assessment resources in molecular diagnostics, CT, next-generation sequencing, respiratory point-of-care testing, remote patient monitoring and immunoassays. These tools can provide companies with baseline market assessments to understand these markets which are more important than ever. We are tracking changes in these markets related to COVID-19 though various upcoming publications.”

Dentists and dental hygienists are currently only caring for critical patients but are generally on the frontlines of public health. We believe these practitioners, along with newly developed point-of-care swab tests, will be a key part of community outbreak monitoring once the virus outbreak is under control. To prepare, DrBicuspid.com has made articles and Continuing Education (CE) courses on infection control and PCR available at no charge for dentists and dental hygienists. Our editorial team, lead by Kevin Henry and Dr. David Rice, are prioritizing content to protect these practitioners and prepare them for serving patients once they are able to get back to work serving their patients.

“We know that dentists and dental team members have a lot of questions right now, including when dental practices might re-open on a full-time basis and be able to care for their full patient database,” said Kevin Henry, Editor-in-Chief of DrBicuspid.com. “Our job is to bring experts together from across the industry to answer these questions as well as providing advice on best business practices to help them overcome the financial hardships brought on by COVID-19.”

Science and Medicine Group will continue to look for opportunities to leverage our broad range of capabilities to assist industry and the scientific and medical communities in increasing testing and the development of therapies and vaccines.

“As the world comes together as friends and neighbors to fight the pandemic, we are proud to provide our MasterFile database to researchers and clinicians,” said Jonathan West, Vice President of Business Development. “They are the true “Superheroes” of our time and the entire Science and Medicine Group team is humbled by the opportunity to support them. “

The FDA approved BioFire FilmArray COVID-19 test, as well as Mesa Biotech’s Accula.  Both can bring a COVID-19 diagnosis to the point of care where testing is most needed.   BioFire’s Film Array has thousands of placements.  Accula is a hand-held test.

https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations

Tests approved with an EUA include:

  • Mesa Biotech Inc. Accula SARS-Cov-2 Test
  • BioFire Defense, LLC BioFire COVID-19 Test
  • Cepheid Xpert Xpress SARS-CoV-2 test
  • GenMark ePlex SARS-CoV-2 Test
  • DiaSorin Molecular LLC Simplexa COVID-19 Direct assay
  • Abbott Molecular Abbott RealTime SARS-CoV-2 assay
  • Quest Diagnostics Infectious Disease, Inc. Quest SARS-CoV-2 rRT-PCR
  • Quidel Corporation Lyra SARS-CoV-2 Assay
  • Laboratory Corporation of America (LabCorp) COVID-19 RT-PCR Test
  • Primerdesign Primerdesign Ltd COVID-19 genesig Real-Time PCR assay
  • Hologic, Inc. Panther Fusion SARS-CoV-2
  • Thermo Fisher Scientific, Inc. TaqPath COVID-19 Combo Kit
  • Roche Molecular Systems, Inc. (RMS) cobas SARS-CoV-2

 

 

Molecular point of care

We projected in Kalorama’s  mPOC market study that molecular point of care ( mPOC ) would lead the fight in meeting the demand for COVID-19 testing with accurate and fast results.   Lab staff is at a premium, hospitals are taxed, and testing needs to happen where it can be useful to isolate patients.  We suggested that Cepheid was a likely candidate for an early EUA, and that has turned out to be the case.   This was based on the company’s track record with Zika and Ebola, as well as a host of other diseases where it has been a first-mover on rapid molecular tests.

As we suggested might happen and as the company predicted, Cepheid has designed a cartridge that uses the existing platform which will save at least 23,000 locations [5,000 US] from having to buy a new instrument.  They company says it will start shipping on March 27th.

Danaher’s Cepheid on Saturday said it has received emergency authorization from the U.S. Food and Drug Administration to use its rapid molecular test for point-of-care patients that can detect the virus that causes COVID-19 in 45 minutes.

We suggested that Cepheid was a likely candidate for an early EUA, and that has turned out to be the case.   Also, as we suggested, the company has designed a cartridge that uses the existing platform which will save at least 23,000 locations from having to buy a new instrument.

Cepheid said the following in a statement: “During this time of increased demand for hospital services, clinicians urgently need an on-demand diagnostic test for real-time management of patients being evaluated for admission to health-care facilities.  An accurate test delivered close to the patient can be transformative — and help alleviate the pressure that the emergence of the 2019-nCoV outbreak has put on health-care facilities that need to properly allocate their respiratory isolation resources,” said Dr. David Persing, MD, Ph.D., chief medical and technology officer at Cepheid.

Other near-patient systems are Credo Biosystems, based in Singapore, which received a CE-Mark for its test, and GenMark’s near-patient e-Plex COVID-19 test, which received an EUA this week.

But Cepheid’s new test is a significant development, for the following reasons:

  • Cepheid has a greater installed base than other systems, and a design that fosters easier use in a clinical setting.
  • The announced speed of 45 minutes is much faster than any approved test we have read of so far, several magnitudes higher than the speed of the approved tests of last week.
  • It  requires no operator training to take the test and determine a result.  This means it can be used in a doctor’s office or retail clinic.
  • 45 minutes is a brief enough time to await results at point-of-care under normal circumstances.
  • Also extraction steps using a kit are not necessary, this is handled in the machine.  There is currently backlogs with such kits at major manufacturers.
  • They are not high-throughput systems, so a test like say a Cobas 6600 in a lab can produce many more test results in a shift, but they are faster so volume is not insignificant.

If one is looking for an example of how fast the IVD industry that Kalorama has observed for two decades can respond to a crisis, this – along with approvals announced by Roche, Abbott, and other firms of mod-complex systems – is evidence.

Demand for testing has gone from a healthcare industry topic to a national crusade in weeks with the onset of COVID-19. High-throughput tests have been approved by the U.S. Food and Drug Administration (FDA) for use in the U.S. for the detection of SARS-CoV-2, the virus behind the disease. But for true intervention in doctors offices — or even airports, many see so-called “point-of-care” (POC) IVD tests as the ideal solution.  A new report on worldwide point-of-care markets from IVD market researcher Kalorama Information has been released amid the coronavirus outbreak. The report has markets for all kinds of near-patient testing — everything from self testing for glucose to rapid HIV tests to cardiac marker tests. Yet the focus in recent weeks has been on tests for COVID-19. Point-of-care tests are tests designed to be portable enough and fast enough to be useful during an one visit or in a decentralized location within a hospital or clinic.

To break a transmission chain, fast access is needed. These tools offer fast access, rather than waiting on texts or doctor’s office staff for restults. Kalorama publishes a report each year on POC markets and has just released its 2020 version: https://kaloramainformation.com/product/the-worldwide-market-for-point-of-care-poc-diagnostics-7th-edition/.

In terms of actual tests for coronavirus tests, there are no U.S. approvals at the time of writing, but products are in development. Molecular POC (mPOC) tests make the most sense because the threat is a virus and can be identified using the gold standard of reverse transcription polymerase chain reaction (RT-PCR). Point-of-care tests are currently used for flu and step tests, including systems by Abbott (ID NOW), Roche (Liat), and Cepheid (Xpert Xpress) mPOC-maker Cepheid says it is developing an automated molecular test for the qualitative detection of SARS-CoV-2. And Cepheid says it will try to utilize its tens of thousands of existing instrument placements. “By leveraging the design principles of our current Xpert Xpress Flu/RSV cartridge technology, in which multiple regions of the viral genome are targeted to provide rapid detection of current and future pandemic coronavirus strains, we are developing a test that can be applied in multiple settings where actionable patient management information is needed quickly,” the company said.

Singapore POC maker Credo Diagnostics Biomedical announced this week that it has obtained the CE mark in Europe for an assay to detect SARS-CoV-2. The test runs on the firm’s platform, called VitaPCR, and the company said it uses PCR and runs the test in 20 minutes. The system needs minimal operator training to run and involves no additional equipment, according to Credo.

The company says the VitaPCR SARS-CoV-2 Assay is now also pending Emergency Use Authorization from the FDA and Emergency Use Listing from the World Health Organization.  While not as fast as immunoassays, the mPOC systems typically use isothermal amplification to achieve much faster turnaround than the regular lab-based RT-PCR tests. This is one of their biggest strengths, along with low. The following are some additional examples of molecular diagnostic systems and assays including POC and other technologies which are available or under development:

  • Aldatu Biosciences – PANDAA qDx SARS-CoV-2
  • Becton Dickinson (BD) – BD and BioGX submitted for EUAs on BD Max platform
  • BGI/ Pathomics Health – Fluorescent RT-PCR kit (CE marked); 2019-nCoV PMseq Kit
  • Bio-Rad – standards – synthetic COVID-19 RNA transcripts and human genomic DNA
  • bioMerieux/ BioFire Defense – FilmArray, BioFire COVID-19 Test
  • Biomeme – Go Strips for  COVID-19
  • BIONEER Corporation – AccuPower 2019-nCoV
  • Caspr Biotech – Phantom 1.0 Dx, disposable test usingCRISPR
  • Cepheid – Test in development for Xpert Xpress system announced; partnership for Sherlock Biosciences’ CRISPR-based SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) engineering biology platform, to design tests to run on Cepheid’s GeneXpert systems
  • CerTest Biotec – VIASURE 2019-nCoV Real Time PCR Kit (CE mark for BD Max platform)
  • Co-Diagnostics – Logix Smart Coronavirus Disease 2019 (COVID-19) Test; single step rRT-PCR (CE mark)
  • Coyote Bioscience – Mini8 Portable Molecular Diagnostic QPCR Station (CFDA approved)
  • Credo Diagnostics Biomedical – VitaPCR platform, COVID-19 assay (CE mark)
  • Curetis/ OpGen/ BGI – RTPCR test kit for SARS-CoV2 (CE mark)
  • Diagnostics for the Real World Ltd – SAMBA II COVID-19 Test
  • GenMark – ePlex SARS-CoV-2 test; sample-to-answer system based on competitive DNA hybridization and electrochemical detection technology (RUO, with EUA submitted)
  • HiberGene – HG Swift, can use battery power, pursuing Fast Track Emergency Use in China
  • Integrated DNA Technologies (Danaher) – 2019-nCoV CDC EUA Kit
  • Jiangsu Qitian Gene Biotechnology Co., Ltd. – Fluorescent RAA Detection for 2019-nCoV
  • LabCorp – COVID-19 reverse transcription polymerase chain reaction (RT-PCR) test (EUA issued)
  • LGC Biosearch – primer and probe kits for CDC Real-Time RT-PCR Diagnostic Panel
  • MiCo Biomed Co. Ltd – VERI-QTM PCR 316 COVID-19 detection system
  • Mobidiag – Novodiag COVID-19 + InfA/B – multiplex test for coronavirus and influenza
  • Molbio – TrueLab, Truenat SARS CoV-2 – TruePrep and TrueNAT instruments
  • Mologic – battery powered point-of-need diagnostic test
  • Novacyt – qPCR (CE mark)
  • OnSiteGene – Peak V
  • Pinpoint Science – SARS-Cov-2 test in partnership with Analog Devices
  • Qiagen – QIAstat-Dx, Respiratory Panel 2019-nCoV
  • QuantuMDx – Q-POC
  • RainSure Bio – DropX-2000 Digital PCR System, RainSure COVID-19 dPCR Detection Kit
  • Randox Laboratories Ltd – Extended Coronavirus Array
  • Seegene – Allplex 2019-nCoV assay (CE mark)
  • Sentinel Diagnostics – Stat-NAT COVID-19 assay
  • SolGent – DiaPlexQ Novel Coronavirus (2019-nCoV) Detection Kit (CE mark)
  • Twist Bioscience – NGS-based target capture for SARS-CoV-2 detection and screening
  • Ubiquitome – Liberty16, open mobile real time PCR system with 2-3 hour battery life

 

In addition to direct tests for SARS-CoV-2, Kalorama expects demand for flu tests to increase due to “rule-out” testing.

Right now, molecular is the focus for the current pandemic, but immunoassays also are in development. Molecular tests generally analyze the viral RNA in patient throat/nasal swabs, but there are other POC testing methods that use immunoassays to detect the patient’s COVID-19 antibodies in blood or serum. It appears there are roles for both mPOC and immunoassay POC tests as there are trade-offs between the two. Immunoassays generally suffer from a high rate of false negatives (low sensitivity), with some rare exceptions. Nonetheless, immunoassays can have comparable speci􀂦city and a varying combination of lower cost, faster turnaround, greater portability, and, thus, advantages in the context of larger-scale population surveillance, screening, and triaging of patients in outbreak situations.

About Kalorama Information

Not since the Swine Flu epidemic of 2009 has there been this amount of emphasis on vaccines and vaccine development.  This new infectious disease threat with no anti-viral, nor vaccine is causing significant concern among healthcare providers, governments and the public.  Last-resort measures such as school closings and curfews in place in the United States has only increased focus on a vaccine solution that could provide enough protections to individuals.

Kalorama covers vaccines markets from 2018 to projected 2024 markets in its market research study: https://kaloramainformation.com/product/vaccines-2018-world-market-analysis-key-players-trends-pediatric-and-adult-segments-influenza-cervical-cancer-combinations-hepatitis-pneumococcal-mmr-varicella-poliovirus-hib-others/
A new report will be out in July 2020.

Some diseases have proven extremely difficult to address through vaccines – HIV, for example. However, although much is unknown about COVID-19, it is nonetheless a respiratory disease that belongs to a class of diseases – corona viruses – that is well understood.  This provides more confidence

We talked with our vaccine analysts to get their sense of the landscape with novel coronavirus.

Early Efforts and a First Trial Dose

COVID-19 vaccine candidates are now heading into trials. Companies in various stages of development include Gilead, GlaxoSmithKline, Pfizer, Moderna, Medicago and others.

Pfizer chairman and CEO Dr Albert Bourla said: “Many companies, including Pfizer, are working to develop antiviral therapies to help infected patients fight this emerging virus as well as new vaccines…Pfizer is working to advance our own potential antiviral therapies and is engaged with BioNTech on a potential mRNA coronavirus vaccine.”

Cambridge, MA-based Moderna announced first participant dose in a Phase 1 trial for mRNA-1273 against the novel coronavirus.  Moderna’s mRNA-1273 is an mRNA vaccine against SARS-CoV-2 encoding for a prefusion stabilized form of the Spike (S) protein. The company’s Phase 1 study is evaluating the safety and immunogenicity of three dose levels of mRNA-1273 (25, 100, 250 μg) administered on a two-dose vaccination schedule, given 28 days apart. A total of 45 healthy adults will be enrolled in the study. Participants will be followed through 12 months after the second vaccination. The primary objective is to evaluate the safety and reactogenicity of a two-dose vaccination schedule of mRNA-1273. The secondary objective is to evaluate the immunogenicity to the SARS-CoV-2 S protein.

This is a major opportunity for vaccine developers, so it is likely that if a developer has a vaccine  that could be even partially effective, they will do everything possible to move it thru trials quickly.   At the same time, governments are looking for more tools to contain the spread. It’s clear that steps taken to date have not been sufficient.   So they are highly motivated to support vaccine development efforts.

Technology 

Demand is not the issue, according to Kalorama’s vaccine analysts.  The market pull will be there, but in vaccine markets, where customers are generally governments, it comes down to the technology – the products.

Some diseases have proven extremely difficult to address through vaccines – HIV, for example. However, although much is unknown about COVID-19, it is nonetheless a respiratory disease that belongs to a class of diseases – corona viruses – that is well understood.  This provides more confidence that it is possible to create a vaccine that would protect some portion of the population.

Since other countries do have significant vaccine development resources – China, India, Japan, etc. – it is certainly possible that a vaccine could be developed overseas before one is developed in the U.S. In fact, I would guess that Chinese vaccine developers began working on this weeks before U.S. vaccine developers.

The Gaurdian reported that about 35 companies and academic institutions are racing to create such a vaccine, at least four of which already have candidates they have been testing in animals.

Stat News reported about an interesting synthetic mRNA solution that is being developed.   https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/ that would be “programmed with the goal of getting our inner machinery to produce certain coronavirus-like proteins — the very proteins that the pathogen uses to gain entry into our cells. Researchers at Moderna and the NIH think that once those homemade dummy virus particles are there, the thinking goes, our bodies will learn to recognize and clobber the real thing.”

Production

Of course, developing a vaccine is only part of the problem. Any vaccine would have to be effectively manufactured and distributed. That could create significant roles for many other players.

Most inactivated influenza vaccines are produced by growing influenza viruses in eggs.  This requires a staggering amount of them. For the H1N1 flu vaccine, a million eggs are required for 3 million doses, more or less.

Egg-based production process begins with candidate vaccine viruses (CVVs) grown in eggs provided by the CDC or approved partner per current FDA regulatory requirements. These CVVs are then injected into fertilized hen’s eggs and incubated for several days to allow the viruses to replicate. The fluid containing virus is harvested from the eggs.

Cell-based flu vaccine has been developed as an alternative to the egg-based manufacturing process. On August 31, 2016, FDA issued an approval for Seqirus, the sole FDA-approved cell-based flu vaccine manufacturer in the United States, to begin using cell-grown CVVs.  Cell culture technology is potentially more flexible than the traditional technology, which relies upon adequate supply of eggs. Recombinant DNA manufacturing is another option. This method does not require an egg-grown vaccine virus and does not use chicken eggs at all in the production process. Instead, manufacturers isolate a certain protein from a flu virus. This proteins are then combined with portions of another virus that grows well in insect cells and allowed to replicate. A protein is harvested from this mix that is used to make the vaccine.

According to a recent article in the Los Angeles times, there are many different vaccine-making platforms, each with its own set of advantages and disadvantages. https://www.latimes.com/science/story/2020-03-12/why-does-it-take-so-long-to-make-a-coronavirus-vaccine “For example, a vaccine based on the virus’ genome can be made quickly, in perhaps a month or two, but it may be harder to manufacture in giant quantities. Another option is to take the virus’ genetic snapshot and put it into a different virus for transport. These vaccines take longer to make — say, six to eight months — but they can be scaled up more readily.”

” almost 33% of readers believe it will take over a year, while slightly more 28% are optimistic there could be a vaccine available within three months.” -Pharmaceutical Technology

An article in Pharmaceutical Technology  said that “Readers of Pharmaceutical Technology have been voting on how long they think it will take for a vaccine to be available to patients. With over 164,000 votes cast, the results show than almost 33% of readers believe it will take over a year, while slightly more 28% are optimistic there could be a vaccine available within three months.”

In general,  this is a very major opportunity for the vaccine industry to shine.  We would expect it to rise to the occasion with at least one, if not several, potential products.  Kalorama will of course report on updates in our biennial vaccine market research study.