It’s an oft-told story that the fortune of Swedish chemist and businessman Alfred Nobel was founded on patented explosives, including dynamite. While his products were used beneficially in mining and construction applications, their wartime use in munitions gave him concern that he would be remembered solely as a ‘merchant of death’. Consequently, Nobel set aside the vast majority of his fortune to establish the prizes that bear his name, awarded to those who have had the greatest benefit on mankind in various fields of endeavor, including the Peace Prize and the Chemistry Prize. This year’s Chemistry Prize was awarded jointly to Emmanuelle Charpentier of France and Jennifer Doudna of the US for their parallel developments of genome editing, namely their groundbreaking 2012 works on CRISPR. Like dynamite, CRISPR offers the twin potential to provide both great risks and rewards to human life.

These and other concerns have produced a variety of moratoria on certain types of research, particularly with respect to human subjects. Nevertheless, the promise of the technology is so great that scientists have a broad array of perfectly ethical and beneficial avenues of research to follow, and are doing so at an ever-increasing rate. In a recently published report from BioInformatics, The 2020 Market for CRISPR/Cas Genome Editing Products, a survey of 328 researchers working with the technology revealed that the number of CRISPR experiments being carried out per month is expected to increase by an average of 16.2% over the next 18 months. The study also offers information on CRISPR workflows, applications and perceptions of vendors and service providers in the space.

CRISPR (clustered regularly interspaced short palindromic repeats) represents a technology developed from the mechanisms underlying a naturally occurring bacterial ability to protect themselves from foreign genetic elements, such as from a viral infection.  From this natural defense has arisen a technology for gene editing, allowing researchers to alter the genetic code with precision, using instruments already found in many life science labs. A gene can be deleted from its location in an organism’s DNA, or novel genes can be inserted into the code. Depending on the application, these changes can be performed on a single cell, or into an entire tissue or organism with an appropriate delivery method.

From the original publications just 8 years ago, a vibrant research community has grown to make use of the technology (as has a vibrant legal industry assessing the patent situation). This revolutionary tool in research and industry does raise some issues of safety. While scientists are generally focused on the positive aspects of treating genetic diseases, developing novel gene therapies, or developing GMO crops with beneficial properties, the legal, ethical and regulatory framework has been slow to develop. This concern is not entirely theoretical or artificial – in 2018, Chinese researcher He Jiankui claimed that he had created the first human genetically edited babies, altering the germline CCR5 gene of twin girls during the embryo stage in an attempt to make them resistant to HIV. Widely condemned by the global scientific community for violating scientific principles and ethical norms, he was fired and sentenced to three years in prison. But in some ways, the genie is now out of the bottle.

What is a Lab-Developed Test?

In vitro diagnostic (IVD) tests are manufactured and sold by diagnostic companies following approval (or clearance) by the appropriate regulatory agencies.  IVD tests are then distributed and used by many different clinical laboratories. In contrast, a laboratory developed test (LDTs) is developed by a clinical laboratory for use specifically in that laboratory.

There are thousands of FDA cleared or approved diagnostic tests, especially when you consider the large numbers of tests that are available for each analyte.  So, why would clinical laboratories develop their own tests?  The answer is simple.  Despite the large number of FDA-cleared or -approved tests and CE-IVD marked tests, there remain many tests that are simply not available commercially for clinical labs to purchase.  If a clinical laboratory wants to offer one of these tests, the lab must develop its own test.

Laboratory developed tests (LDTs) are not a recent phenomenon but due to the urgent need for testing of SARS-CoV-2, there has been a flood of new tests and the regulatory guidance has changed dramatically. Historically, these tests were low-volume, simple and well characterized for low-risk diagnostic applications. Today, high-risk, complex tests have been developed as LDTs, and are being used to provide clinical results to physicians and their patients.

Kalorama’s Report Estimates a 12 Billion Dollar Market  for LDTs

he market for LDTs offered as services is worth over $12 billion, as indicated in this sample below from tbe Kalorama Information’s newest report:

 

LDT Revenue Growth

 

The LDT clinical services market is a large field that covers a wide range of activities, and this is reflected in the topics covered in this report.  This report includes discussions of:

  • Overview of laboratory developed tests (LDTs), including technologies used in LDTs and products sold to laboratories developing and performing LDTs
  • Clinical applications for which LDTs are used
  • Market drivers and challenges in the LDT market
  • Sales for 2020 and projected to 2025 – LDT clinical diagnostic test services
  • Sales for 2020 and projected to 2025 – Products sold to laboratories offering LDTs
  • Profiles of companies in the LDT market

Information used to calculate the market sizes for the LDT clinical diagnostic service market were derived from a wide range of sources including public information about company sales; interviews with market participants including executives, marketing managers and product managers; Kalorama’s databases; and other industry sources.

This Market is Driven by Regulation and Changes in Regulation

The FDA has indicated that it would like to increase oversight of laboratory develop tests for many years.  In July 2014, the FDA notified Congress that it plans to issue a draft guidance entitled “Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs).  On September 30, 2014, the FDA posted two draft guidances to its web site:  “Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)” and “Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).”  The comment period for both of these documents lasted until February 2, 2015.

This has created considerable uncertainty.  While has not been possible to know what the final guidance documents would say, it was clear that the FDA wants to increase oversight of LDTs, and to require 510(k) clearance or PMA approval of many LDTs.

The future of regulation of LDTs is even more uncertain now.  In November 2016, in the wake of uncertainty following the presidential election, the FDA indicated that it would delay finalizing the draft guidance on LDTs.  On January 13, 2017, the FDA issued a “Discussion Paper on Laboratory Developed Tests (LDTs).”  This discussion paper synthesizes feedback that the FDA received on the 2014 draft guidance and proposes a prospective oversight framework.  Some of the proposals in the discussion paper include “grandfathering” LDTs (except when required to protect public health), exempting certain categories of new or significantly modified LDTs, reduced time-frame for phasing in regulation of LDTs with risk-based and phased-in oversight, evidence standards, third-party review, clinical collaboratives, transparency, quality system requirements, and post-market surveillance.

Due to the need for coronavirus testing discussed above, the regulatory process is again being scrutinized. It has been planned that the FDA would step up oversight of LDTs after the 2016 election. However, that is not happen. The regulatory boat was stagnant.

At the start of the pandemic, FDA stressed the  need for availability of coronavirus tests developed by laboratories and commercial manufacturers to meet the testing needs.

In March 2020, a bipartisan-backed bill called the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was introduced to Congress. The VALID Act would create a new risk-based oversight framework for in vitro clinical tests, a category that was owned by LDTs and test kits.  That was followed by a bill introduced later in the month by Senator Rand Paul called the Verified Innovative Testing in America Laboratories (VITAL) Act which would take regulation of LDTs out of the FDA’s hands.

In September 2020, the FDA was directed by the U.S. Department of Health and Human Services (HHS) to drop its pursuit of regulation of LDTs. Both the ACLA and the Association for Molecular Pathology backed the move of HHS.  HHS stated that the move is a part of their ongoing department wide review of regulatory flexibilities enacted since the start of COVID-19. There continues to be mixed responses to the latest HHS move. Critics are concerned that this could negatively impact the accuracy of individual labs’ tests, allowing unreliable tests to come to market. This is probably not the last that we will hear about this controversy.

This a Unique Market to Quantify

Estimating revenues for products sold to these laboratories is more challenging as a result of many factors.  For example, a laboratory may purchase an instrument with the intention of using that instrument to perform FDA cleared or approved tests and also LDTs on that instrument.  Alternatively, a laboratory may purchase a research instrument, and then validate and use LDTs on that instrument as well as potentially performing some studies.  Also, clinical laboratories may use consumable reagents for applications that were not intended by the manufacturer.  For example, a clinical laboratory may use an FDA cleared or approved test on a non-approved type of specimen after the required validations have been completed for the LDT.  In this example, the reagents used by the clinical lab for the LDT may be reported by the diagnostic company as an IVD product, and not as a component of an LDT.  These are just a few of the challenges to be faced when estimating the size of the market for products sold to clinical laboratories for use in LDTs.

Oncology LDTs Lead

Much of the focus and attention in recent years has been on the emergence and growing use of complex LDTs based on technologies such as polymerase chain reaction (PCR), microarrays, and next generation sequencing.  To generate test results that were not previously possible, LDTs are being developed and used in many different applications.  The largest segments of this market are oncology, genetic (inherited) disorders, and infectious disease, but laboratory developed tests can be developed and used for virtually all disorders.

Urgent care’s story in the United States has been all about growth.  They offer walk-in care and a range of services, expanded hours and limited wait times.  They usually have imaging equipment and multiple providers and are in a freestanding location or a dedicated store within a retail strip mall.  With approximately 10,000 locations across the country, urgent care clinics (UCCs),  are an increasingly important part of the U.S. health care marketplace.

The concept is not new.  There are many urgent care centers in operation 30 years or more.  There are urgent care centers operating longer than the primary practices surrounding them.  But in a sense, urgent care as it exists now is new in that the awareness and utilization of these centers increased greatly.

Growth, with Limits

Urgent care centers are expected to grow in three distinct ways, according to the latest Kalorama Information report.   They will grow in the number of locations, there will be more patients visiting them each day, and the centers will earn more revenue from them.  The three factors have a multiplier effect.  This will lead to a 24.8 billion-dollar market in 2020 and growth near eight percent.

However, urgent care growth will be limited by the competition and saturation of markets, and competition from retail clinics, and extended hours at physician offices.  The sheer amount of locations is draining the available patient population.  Some insurance carriers will no longer pay urgent care fees in saturated markets such as NY/NJ and Florida.  This compounded by the trend of seniors tending to use physician care rather than urgent care does set a limit on the amount of locations there can be in the U.S. in the future.  The market is not mature, but the maturation point is visible.

“76.6% of the U.S. population resides within a 10-minute drive to an urgent care center.” – Urgent Care Association

This is good news for urgent cares, but also means there are limits to growth.    The industry will not be a “boom mode” forever.  The fastest growth, Kalorama estimates, happened in the early part of this decade, between 2011 and 2017.  There are limiters to growth as well as drivers, and there is increasing visibility on those limiters. It is estimated a population of 50,000 is needed to fuel an urgent care center.  The U.S. has already past the saturation point in urban areas, though rural areas with limited healthcare remain sources of growth.

Urgent Care and Its Competitors

What distinguishes urgent care centers is that they are a walk in clinic offering extended hour access for acute illness and injury care that is either beyond the scope or availability of the typical primary care practice but offer less services than an emergency room would.

The urgent care clinic concept has shown potential to provide affordable, accessible and quality medical care to consumers who otherwise would have to wait hours, days, or even weeks for care. They also provide an alternative to costly, time-consuming emergency room care for sicknesses that could have been prevented if basic health care services had been available.

Table 1-1: Urgent Care Centers vs. Retail Clinics and Physician Practices

Characteristic Urgent Care Center Retail Clinic Physician Practice
Accepts insurance Yes Yes Yes
Appointment required No No Yes
Extended hours Yes Yes Sometimes
Located in a retail store, typically a drug store No Yes No
Freestanding or in its own space Yes No Yes
Physician on-site Yes No Yes
Treats broken bones Yes No Yes
X-ray and/or ultrasound on-site Yes No Rarely
Treats cuts & lacerations Yes No Yes
Treats complicated conditions No No Yes
Specialists on-site No No Sometimes

Urgent care’s sales pitch is its savings over ER.  For example, a 2010 Health Affairs report pointed to cost saving potential, finding that up to 27% of emergency department cases could be seen in urgent care; such a transition would generate up to $4.4 billion in annual cost savings.  This has mostly held.  A more recent white paper from the Urgent Care Association of America estimated that the cost savings of using urgent care centers versus emergency departments could amount to as high as about $18.5 billion per year.

For these reasons, rising rates of utilization are leading to substantial profits for providers, which is in turn fuelling further expansion. More than half of US centers have been open more than 5 years, however, new centers continue to open and existing UCCs continue to expand.

The urgent care business model involves providing a full range of services of nonemergency acute care. UCCs differ from traditional physicians’ offices with procedure rooms for lacerations and fractures, a radiology department for x-ray services, and a laboratory.

More information can be found at Kalorama Information’s report: https://kaloramainformation.com/product/the-u-s-market-for-urgent-care-centers/

It’s beyond theory.  The microbiome is one of many trends that align well with the IVD market.  It is explored in Kalorama Information’s study of the in vitro diagnostic market, The Worldwide Market for In Vitro Diagnostic Tests along with other trends such as automation and gene editing.   The continuous search of the etiology of diseases as part of the body’s systemic response to change has led to a consideration of the gut microbiome as part of disease processes.  While still in the early phase of development a number of companies have developed assays for the study of the microbiome and there is a proliferation of microbiome related therapeutics.

Bacteria in the gut, mouth and plaque (biofilms) have been implicated in a number of diseases including diabetes, obesity, autoimmune, cancer, diarrhea, and mental disorders.  Thousands of species of microbes—bacteria, viruses, fungi, and protozoa—inhabit every internal and external surface of the human body.  The microbiome’s complicated relationship with its human host is increasingly considered crucial to health.  Imbalances in the microbiome’s diverse microbial communities, which interact constantly with cells in the human body, may contribute to chronic health conditions, including diabetes, asthma and allergies, obesity and the metabolic syndrome, digestive disorders including irritable bowel syndrome (IBS), and autoimmune disorders like multiple sclerosis and rheumatoid arthritis.

The microbiome skincare market is expected to continue to grow by double digits in every country researched (United States, Germany, Korea, Japan, Thailand, and China).  The primary drivers for its growth are the natural wellness trend, the fear of chemicals, increasing influence of environmental stressors, and pharmaceutical company investment.  In fact, recent television ads for skin care soaps in N. America state the product “keeps the skin’s natural microbiome intact.”  There are of course probiotics and books that direct consumers to maintain a healthy gut for overall wellness.

While still in the early phase of development a number of companies have developed assays for the study of the microbiome and there is a proliferation of microbiome related therapeutics.

Intense research into the relationship of a person’s population of normal flora and pathogenic invaders with the etiology and progression of disease states has been developed into microbiome-based molecular tests.  Some IVD companies are already developing a greater appreciation for the microbiome’s contributions to human biochemistry and have launched tests to measure changes in the microbiome to monitor disease progress.  At this time, most testing is available from service providers and for research.  There are however at least two CE Marked test kits available from Genetic Analysis (Oslo, Norway) and Luxia Scientific (France)

Researchers also evaluate specific diseases associated with disturbances in the microbiome, including gastrointestinal diseases such as Crohn’s disease, ulcerative colitis, irritable bowel syndromes, and obesity, as well as urogenital conditions, those that involve the reproductive system, and skin diseases like eczema, psoriasis, acne, obesity, diabetes, autoimmune disorder, acute diarrhea, cancer, mental disorder, and others.

Of interest are the CE Marked tests from Genetic Analysis (Oslo, Norway).  Genetic Analysis was awarded the CE Mark for its Dysbiosis test for microbiome imbalance in irritated bowel syndrome.  Genetic Analysis has developed GA-map technology, the first gene-based routine test for the mapping and aide in diagnosis of diseases associated with dysbiosis and imbalances in the bacteria in the digestive system.  Genetic Analysis was established in 2008 and is based on research done by Professor Knut Rudi at Norwegian University of Life Sciences.

In 2018, Luxia Scientific (Paris, France) was awarded the CE Mark for its 1test1 that analyzes the bacterial content of the gut microbiome.  Leveraging 16S rRNA sequencing, it provides information about bacterial diversity and the relative abundance of many bacterial groups that provide beneficial health benefits, (according to Luxia).   In March 2018, Luxia announced an exclusive distribution agreement with Life Genomics (Sweden) whereby Life Genomics will exclusively distribute Luxia’s 1test1 test in Sweden, Denmark, Finland, Iceland, and Norway.

Other IVD industry initiatives include:  OraSure Technologies (Bethlehem, PA) is best known for its point-of-care diagnostic tests for infectious diseases and molecular sample collection devices.  In January 2019, OraSure acquired CoreBiome (St. Paul, MN) an early-stage microbiome services provider for customers in the pharmaceutical, agricultural, and research communities.  The company’s slogan is “Powering microbiome science with big data”.  CoreBiome’s technology provides information-rich characterization of microbial diversity and function, paired with machine learning and expert analytics.  CoreBiome’s BoosterShot platform allows researchers to efficiently run high-resolution DNA sequencing on thousands of microbiome samples.  OraSure indicated that CoreBiome’s microbial genomics technology will complement the company’s DNA Genotek’s molecular sampling business.

Bio-Rad Laboratories entered into a collaboration with Genetic Analysis AS (Oslo, Norway) and Bioaster, a French microbiology research institute, to study gut microbiome alterations in metabolic disorders.  The project will look for microbiota signatures of dysbiosis in metabolic disorders like diabetes and obesity in order to pursue diagnostics development.  It will use Bioaster’s deep and 16S-targeted sequencing technologies and advanced pipelines of data analysis for highlighting new gut microbiome biomarkers, according to a statement.

Bio-Rad acquired the distribution rights for the CE Marked GA-Map test made by Genetic Analysis (Oslo, Norway).  The assay tests for gut microbiota and detects bacterial imbalances to diagnose and manage conditions such as inflammatory bowel disease and irritable bowel syndrome to detect imbalances in the gut microbiome.  GA-map uses 16S rRNA amplification and a number of proprietary analysis technologies.

Thermo Fisher launched the Applied Biosystems Axiom Microbiome Array for simultaneous detection of archaea, bacteria, fungi, protozoa and viruses in human and non-human samples. Developed in collaboration with the Lawrence Livermore National Laboratory (LLNL), the array is designed to increase the understanding of microorganisms, while accelerating the translation of these insights into human health and agricultural applications.

According to Thermo Fisher, a major advantage of the array, which incorporates sequences for over 12,595 species in the National Center for Biotechnology Information (NCBI) archive, is the simultaneous detection of protozoa and viruses and ease of analysis, a capability that is not available with 16S or other platforms.  Most recently, the Axiom Microbiome Array won the R&D 100 Award, which honors great R&D pioneers and their revolutionary ideas in science and technology.  Awarded by R&D magazine, and considered the “Oscars of Innovation”, the R&D 100 Awards recognize and celebrate the top 100 technology products of the year.

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.

 

A rapid scale-up of diagnostic testing for the novel coronavirus was the focus of a declaration of emergency by President Donald Trump in a March 13 press conference. The plan calls for sharply boosting the production of coronavirus test kits while also making tests available at a network of drive-through sites.

In an address at the White House Rose Garden, Trump announced a series of sweeping measures designed to eliminate government regulations that may have been hindering the federal response to the coronavirus outbreak. Most of Trump’s address was devoted to the administration’s plans for making diagnostic testing more available across the country — an issue that has become a flash point for criticism of the administration’s response to the virus.

In his emergency declaration, Trump said that previous government regulation included “very old and obsolete” rules. The new declaration would enable the U.S. Department of Health and Human Services (HHS) to waive rules that may have impeded hospitals and healthcare providers from responding adequately to the coronavirus outbreak. The declaration would also make available $50 billion in federal funding to fight the outbreak.

But Trump reserved the lion’s share of his speech to explain what the administration is doing to make diagnostic test kits more available to test for SARS-CoV-2. Healthcare providers and clinical labs in the field have complained that they have not had enough coronavirus tests available to meet demand, and some have claimed that testing criteria have been too restrictive.

The new plan relies on a combination of making more testing capacity available and at the same time making it easier for Americans to get tested, such as with drive-through testing sites. The administration is also working with Google to set up a website that will enable Americans to determine on their own whether they should seek out testing.

With respect to testing capacity, Trump explained the work the administration has been doing with diagnostics manufacturers such as Roche and Thermo Fisher that builds on a meeting between diagnostics vendors and the government last week.

Roche developed a high-throughput test for the coronavirus, cobas SARS-CoV-2, that received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) within 24 hours of submission of an application. The test’s high-volume capacity should be a step forward in meeting demand for coronavirus testing, Trump said.

FOR MORE INFORMATION

https://www.labpulse.com/index.aspx?sec=sup&sub=mic&pag=dis&itemid=800889

 

Molecular point-of-care diagnostic solutions offer improvements in the sensitivity and specificity of existing near-patient and rapid tests while expanding the diagnostic capabilities at points of care, such as hospital critical care units, physician offices, outpatient clinics, and community health posts in the developing world, and are used to assess conditions or admit patients.  The concept of molecular point of care is to mix the accessibility of POC testing with the accuracy of molecular technology. Kalorama has covered molecular point of care on a yearly or biyearly basis since 2013. Our latest report found slower system adoption, but brisk consumables sales and the continued hope of test menu expansion.

The molecular point of care segment, the focus of the report, includes only the small/ portable models and defines the molecular POC/ near-POC market as:

  • Systems that are CLIA-waived, or could soon have or potentially have the capability for running CLIA-waived tests.
  • Systems that can run moderate-complexity or high-complexity tests in a decentralized setting such as a non-laboratory area of a hospital or a physician office/ clinic visit.
  • Tests with a short waiting period for the results, making it practical and useful for POC.

This may differ from other definitions of point of care.  The mPOC systems have great sensitivity and scalability, and they won over early adopters but have had difficulty making the case for routine adoption.  As was asked at the Association for Molecular Pathology (AMP) meeting panels last year: Is the juice worth the squeeze? And there’s not a true answer yet. These systems will have to prove to gain new placements.

“Our latest report found slower system adoption, but brisk consumables sales and the continued hope of test menu expansion.”

The overall revenues estimate for this “true” mPOC segment is provided below. This segment is largely made up of tests for the flu and other respiratory diseases.    However, they are earning consumables sales from the placements they have.  As presented, the revenues for this segment are forecast to increase from $360 million to $852 million between 2019 and 2024, with a compound annual growth (CAGR) of 18.8%.

Kalorama also details another segment: more than $2 billion of “near-patient” systems that are not aimed at decentralized testing areas and require users to have technical competency.

Molecular systems need to prove marginal worthiness in the clinical setting as they have a higher cost.    Molecular tests tend to have much higher sensitivity and specificity, even 100%, but lab-based nucleic acid amplification tests were historically slower and required more expertise to run. Now with mPOC systems, the question will turn on marginal difference in sensitivity over immunoassay systems, and this will be driven by journal literature and clinical practice changes.

Justification for purchases of molecular point-of-care instruments and reagents are dependent on the argument of superior sensitivity and specificity. In this regard, the findings from a January 2020 Journal of Clinical Microbiology study are welcome news.  Major CLIA-waived mPOC systems were compared with immunoassay systems. Molecular had high-90s sensitivity, whereas the tested immunoassay system had high sensitivity of 80% and a sensitivity for influenza B of 67%. Not being able to establish a “true-negative” test has been a frustration of providers using rapid immunoassay tests.

 

March 9, 2020 — The revival of legislation to change the regulation of laboratory-developed tests (LDTs) has drawn a mixed response. The reintroduction of the Verifying Accurate, Leading-edge IVCT Development (VALID) Act is intended to remove barriers that are believed to have impeded the U.S. government’s response to the coronavirus epidemic.

The issue of diagnostics regulation has emerged as a political lightning rod, with some faulting the Trump administration’s response to the outbreak and others blaming what they claim is a history of federal overregulation of clinical labs.

“The industry associations that produce commercial IVD kits and pathologists who are concerned about overcommercialization of lab tests are clashing with representatives of the laboratories themselves.  These opinions represent longstanding positions of the players.”

Clinical labs are regulated by the U.S. Centers for Medicare and Medicaid Services (CMS) under CLIA and are not typically subject to oversight by the Food and Drug Administration (FDA). However, the FDA does regulate individual diagnostic tests, with diagnostic manufacturers required to gain FDA approval to market their assays. Yet another regulatory category, laboratory-developed tests, are tests that labs can develop and use on their own.

The situation has created several hurdles in responding to the novel coronavirus. When the FDA declared the coronavirus a public health emergency, it triggered a requirement that labs in the field get the FDA’s blessing to use their LDTs for the virus. The FDA subsequently waived this rule on February 29, but the need for a permanent solution to the regulatory environment is apparent…

To read more, please visit LabPulse.com: https://www.labpulse.com/index.aspx?sec=sup&sub=lab&pag=dis&ItemID=800854

 

coronavirus

The House of Representatives and Senate today passed an $8.3 billion spending package to help providers and local governments handle the spread of the coronavirus and to boost the development of vaccines and tests of the virus.  While vaccine support and spending on healthcare is expected, the bill also  boosts telehealth solutions with financial support and positive regulatory changes. 

Telehealth, or as Kalorama defines it, remote patient monitoring, is a $42-billion dollar market

The coronavirus response bill released by Congress on March 5th expands the Medicare reimbursement for  providers using who treat patients via telehealth to treat seniors at home.  The emergency spending bill waives Medicare’s geographical restrictions on telehealth during a public health emergency, enabling providers to use telehealth in both urban and rural areas as well as in the patient’s home as part of an “emergency area.”  Previously this was limited to rural areas.  It also loosens definition on telehealth devices, essentially allowing any device connecting physician and patient with audio and video capabilities.  This is a significant boost for telehealth and is understandable given the spread of the disease and the need to both service patients and protect physicians, nurses and other staff.

Most importantly, the bill contains mandatory funding authorization for $500 million over 10 years to be used toward a remote health care program.

This is a boost for the patient monitoring and telehealth market.  Kalorama Covers Remote Patient Monitoring in This Report: https://kaloramainformation.com/boost-for-42-billion-dollar-remote-patient-monitoring-market-in-covid-19-bill/

The global patient monitoring and telehealth market is estimated to be worth about $42 billion in 2019, inclusive of devices, peripherals, software, packaged services, monitoring services and other applications.  The market has benefited from the demand to move to a more wireless and streamline operation both within major health facilities and in-home treatment markets.  The demand to integrate data processing capabilities and EMR transfer options has also fueled the market.  There is also an increasing trend to upgrade to ambulatory and hand-held devices.

No longer is telehealth for rural patients alone.  For qualified providers, an emergency waiver will allow telehealth to be reimbursed by Medicare.   And extra funding is provided.

The interest in telemedicine and telehealth has exploded over the last decade.  Involvement in this care segment has several benefits and hospitals, caregivers, device manufacturers, and patients are continuing to jump on board with acceptance using this technology.  There are more than 700 clinical trials using telehealth recently completed, currently underway.  The global patient monitoring and telehealth market has continued its expansion in both the institutional and home segments of the health market with the United States and many European countries at the forefront of implementation.

 The industry spoke in the past few days and Congress listened.  In a recent letter sent to Senate Majority Leader Mitch McConnell, R-Kentucky, House Speaker Nancy Pelosi, D-California, and other Congressional leaders, the ATA – along with HIMSS, the eHealth Initiative, Health Innovation Alliance and Personal Connected Health Alliance – has asked Congress to make money from the COVID-19 supplemental appropriation available for more telehealth services.

Unique Opportunities in Telehealth/Telemedicine

There are a number of market opportunities in telemedicine that may offer some benefits over traditional office-based care.

For example, AMD Telemedicine’s General Exam Camera and Telephonic Stethoscope were used in a pilot program to treat Illinois inmates with HIV and Hepatitis.   Other examples include using telehealth to address the growing need for mental health monitoring and intervention.  This is an area where interest has increased significantly, as barriers to treatment are three-fold: lack of treatment resources; lack of adequate medical coverage; embarrassment.

Mental Health Assessment through Telemedicine

Telemedicine in the area of mental health disorders and conditions is often referred to as telemental health or telepsychiatry.

One area of mental health therapy is PTSD a type of anxiety disorder brought on by very traumatic situations such as war.

The costs of PTSD are difficult to accurately pinpoint because it may manifest itself in different ways for different people. Some patients seek therapy in unhealthy methods such as through alcohol and drugs. Lost wages, mortality, therapy sessions, physical health problems (non-psychiatric care), and prescription drugs are all costs associated with treating PTSD.

Caregivers may use telepsychiatry when they move or if the patient moves. Telehealth has the potential to increase the time a patient can see one caregiver, which has been linked to improved care, and can be beneficial for the worker who can keep some of their income after a move, even if it is only on a part-time basis.

Currently, in traditional fee-for-service Medicare, use of the telehealth benefit is limited to rural Health Professional Shortage Areas (HPSA1), CMS defined telehealth originating sites, and synchronous telehealth services. The Next Generation ACO Telehealth Expansion Wavier eliminates the rural geographic component of originating site requirements, allows the originating site to include a beneficiary’s home, and for the use of asynchronous telehealth services in the

specialties of teledermatology and teleophthalmology.

The waiver will apply only to beneficiaries aligned to a Next Generation ACO and for services furnished by a Next Generation Participant or Preferred Provider approved to use the waiver.  An aligned beneficiary will be eligible for the Telehealth Expansion Waiver if the beneficiary is located at their home or one of the Centers for Medicare & Medicaid Services (CMS) defined telehealth originating sites.

Medicare currently covers a limited number of Part B services delivered by an approved provider to a Medicare beneficiary. The beneficiary must be located in an approved “originating site” and services must be delivered by face-to-face consult using live video conferencing technology.   Originating site under existing Medicare telehealth rules include.

– Physicians’ or practitioners’ offices

– Hospitals

– Clinics and federally qualified health centers

– Hospital-based renal dialysis centers (including satellites)2

– Skilled nursing facilities (SNFs)

– Community mental health centers

There are a huge number of companies offering some form of wireless and remote technologies, patient data processing applications and equipment, and EMR data transfer equipment.  Competitors supplying patient monitoring and telehealth systems to hospitals are large, established healthcare companies, often working in conjunction with information technology (IT) companies on an entire system.  The home healthcare and other sectors are much more fragmented and are dominated by privately held companies.  In addition, some companies supply innovative products, but only for a small segment of the market; and some companies supply products on a regional basis only.

Although there are many participants in the market, a handful of companies continue to make a significant impact on the patient monitoring and telehealth technologies market.  The top five contributors to the market include:

  • Medtronic
  • Abbott Laboratories
  • Philips Medical
  • Boston Scientific
  • GE Healthcare