Mesa Biotech Obtains CE Mark for its Accula RSV Molecular Point of Care Test

Mesa Biotech Inc., a privately-held, molecular diagnostic company that has developed an affordable and easy to operate PCR (polymerase chain reaction) testing platform designed specifically for point-of-care (POC), today announced it has obtained CE Mark in the European Union (EU) for its Accula™ RSV Test. The company's RSV test will be marketed by select distributors in the EU at once. Accula RSV Test is pending FDA clearance in the US.

"We are excited to introduce the second test in our PCR-based infectious disease diagnostic portfolio in the EU," said Hong Cai, Co-founder and Chief Executive Officer, Mesa Biotech, Inc. "The Accula RSV brings reference laboratory performance to the point of care, enabling clinicians to quickly and accurately diagnosis and treat their patients."

Respiratory syncytial virus (RSV) is an RNA virus attributable to outbreaks of respiratory tract infections. RSV infections can occur throughout the year, but typically peak during the winter months. Studies indicate that nearly 100 percent of children will suffer from RSV infections by age two. RSV viruses not only cause upper respiratory tract infections but also bronchiolitis of the lower respiratory tract, which often becomes severe in infants and toddlers with underlying diseases. Diagnosis of RSV is difficult because the initial symptoms can be similar to those caused by other infectious agents. Considering that the RSV virus is highly contagious, accurate diagnosis and prompt treatment of patients can have a positive effect on public health.

According to the World Health Organization (WHO), the global burden of RSV-associated acute lower respiratory infection is estimated at 33 million annually, resulting in more than 3 million hospitalizations and almost 60,000 in-hospital deaths in children under five years of age.

The Center for Disease Control (CDC) acknowledges that the specificity and sensitivity of rapid influenza diagnostic tests (RIDT) are lower than for viral culture and RT-PCR and vary by test.  The Accula System, a palm-sized, reusable dock with disposable test cassettes, offers the simplicity, convenience and procedural familiarity of traditional POC rapid immunoassays, while providing the superior sensitivity, specificity and information content of laboratory-based PCR testing. The Accula RSV test is indicated for use with nasal swab collection, which is less invasive than nasopharyngeal swabs and provides a more comfortable specimen collection experience for the patient, especially children.

About Mesa Biotech Inc.

Mesa Biotech designs, develops, manufactures and commercializes next generation molecular diagnostic tests, bringing the superior diagnostic performance of nucleic acid PCR amplification to the point-of-care (POC). Mesa Biotech's Accula™ System consists of a portable, palm-sized dock and disposable, assay-specific test cassettes. This patented system enables healthcare professionals to access actionable, laboratory-quality results at the POC with greater sensitivity and specificity than current infectious disease rapid immunoassay tests. The Accula Flu A/Flu B Test, Mesa Biotech's first product to market, has obtained CE Mark in the EU and 510(k) clearance and Clinical Laboratory Improvements Amendments (CLIA) waiver from the U.S. Food and Drug Administration (FDA).

Bio-Rad Wins USDA Contract for Its Pathogen Detection Testing Products

Bio-Rad Laboratories, Inc., a global leader of life science research and clinical diagnostic products, today announced that the company has been awarded a contract for iQ-Check real-time PCR pathogen detection test kits and the iQ-Check Prep Automation System from the United States Department of Agriculture’s Food Safety and Inspection Service (USDA FSIS).

The contract includes real-time PCR-based tests for pathogens that include Salmonella spp., Listeria monocytogenes, Campylobacter, Escherichia coli O157:H7, and Shiga toxin producing E. coli (STEC) that may be found in raw meat and poultry, ready to eat meat and poultry, processed egg products, and other food products and environmental samples. Bio-Rad’s iQ-Check real-time PCR test kits were selected based on their proven real-time PCR technology that uses highly specific patented DNA probes to detect pathogenic bacteria in a sample. USDA FSIS will also incorporate Bio-Rad’s iQ-Check Prep automation system for high throughput sample processing and elevated traceability.

“We are pleased to partner with the USDA to help protect the food supply,” said Annette Tumolo, Bio-Rad President, Life Science Group. “This is an exciting development for Bio-Rad, reflecting our strong performance in the area of rapid food pathogen testing solutions.”

The iQ-Check kits for pathogen detection are routinely used in food safety programs worldwide, and are recognized by several renowned international validation organizations.

iQ-Check and Bio-Rad are trademarks of Bio-Rad Laboratories, Inc. in certain jurisdictions.

FDA Authorizes Emergency Use of First Ebola Fingerstick Test with Portable Reader

The U.S. Food and Drug Administration announced that an emergency use authorization (EUA) has been issued for a rapid, single-use test for the detection of Ebola virus (Zaire ebolavirus). This is the second Ebola rapid antigen fingerstick test available under EUA, but the first that uses a portable battery-operated reader, which can help provide clear diagnostic results outside of laboratories and in areas where patients are likely to be treated.
The test, called the DPP Ebola Antigen System, is used with blood specimens, including capillary “fingerstick” whole blood, from individuals with signs and symptoms of Ebola virus disease (EVD) in addition to other risk factors, such as living in an area with large numbers of EVD cases and/or having contact with other individuals exhibiting signs and symptoms of EVD.

“The scourge of Ebola tragically demonstrates that we’re a global community when it comes to public health protection. Infectious disease doesn’t recognize nation states. Bacteria and viruses don’t respect territorial boundaries. It takes a sustained, robust and globally coordinated effort to protect our nation and the global community from various infectious disease threats. We’re all in this together. To that end, our FDA team of experts in drugs, vaccines and diagnostics continue to collaborate with our Federal, international and industry partners to employ our collective expertise, experiences from previous incidents, and resources to assist in the global response to the Ebola outbreak in the Democratic Republic of Congo,” said FDA Commissioner Scott Gottlieb, M.D. “This EUA is part of the agency’s ongoing efforts to help mitigate potential, future threats by making medical products that have the potential to prevent, diagnosis or treat available as quickly as possible. We’re committed to helping the people of the DRC effectively confront and end the current Ebola outbreak. By authorizing the first fingerstick test with a portable reader, we hope to better arm health care providers in the field to more quickly detect the virus in patients and improve patient outcomes.”

The FDA’s EUA authority allows the agency to authorize the use of an unapproved medical product, or the unapproved use of an approved medical product when, among other circumstances, there are no adequate, approved and available alternatives. When circumstances exist justifying authorization, the EUA becomes an important mechanism that allows broader access to medical products that have not been FDA cleared or approved and are instead only authorized for use for the duration of an emergency declaration. The FDA’s criteria for issuing an EUA for a diagnostic test includes making an assessment that it is reasonable to believe, based on the totality of evidence available to the agency, that the test may be effective and the known and potential benefits of using the test outweigh its known and potential risks.

In 2014, during the Ebola outbreak in West Africa, an emergency was declared by the Secretary of Health and Human Services. While that outbreak has ended, ongoing, smaller Ebola outbreaks have continued, and the emergency declaration is still in place. Recent outbreaks in remote areas with limited resources can benefit from rapid diagnostic tools, and the issuance of an EUA for the DPP Ebola Antigen System is an important step in addressing these outbreaks.

The DPP Ebola Antigen System provides rapid diagnostic results with tests that can be performed in locations where a healthcare provider does not have access to authorized Ebola virus nucleic acid tests (PCR testing), which are highly sensitive but can only be performed in certain laboratory settings that are adequately equipped. The DPP Ebola Antigen System has been authorized for use with capillary “fingerstick” whole blood, ethylenediaminetetraacetic acid (EDTA, an anticoagulant added to whole blood to prevent coagulation) venous whole blood and EDTA plasma. The DPP Ebola Antigen System should only be run in facilities, including treatment centers and public health clinics where patients are likely to be treated, and laboratories that are adequately equipped, trained and capable of such testing.

While today’s action will increase access to diagnostic tools for healthcare providers who may not have otherwise been equipped to perform tests, it is important to note that a negative result from the DPP Ebola Antigen System, especially in patients with signs and symptoms of EVD, should not be used as the sole basis for patient management decisions. The diagnosis of EVD must be made based on multiple factors such as, history, signs, symptoms, exposure likelihood and other laboratory evidence in addition to the detection of Ebola virus.

The FDA remains committed to using its authorities and resources to advance the development of countermeasures to address emerging threats and recently outlined its efforts to help address Ebola virus outbreaks. The FDA will continue to work with its federal partners and potential commercial product manufacturers in the most expedited manner to increase the availability of authorized diagnostic tests for Ebola virus disease for emergency use during this and any future outbreak.

With the issuance of the EUA for the DPP Ebola Antigen System to Chembio Diagnostic Systems Inc., the FDA has now issued EUAs for nine nucleic acid tests and two rapid diagnostic tests for Ebola virus detection in human specimens.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Cellphone Technology Developed to Detect HIV

The management of human immunodeficiency virus 1 (HIV), an autoimmune disorder that cripples the immune system by attacking healthy cells, remains a major global health challenge in developing countries that lack infrastructure and trained medical professionals. Investigators from Brigham and Women’s Hospital have designed a portable and affordable mobile diagnostic tool, utilizing a cellphone and nanotechnology, with the ability to detect HIV viruses and monitor its management in resource-limited regions. The novel platform is described in a paper published recently in Nature Communications.

“Early detection of HIV is critical to prevent disease progression and transmission, and it requires long-term monitoring, which can be a burden for families that have to travel to reach a clinic or hospital,” said senior author Hadi ­­Shafiee, PhD, a principal investigator in the Division of Engineering in Medicine and Renal Division of Medicine at the Brigham. “This rapid and low-cost cellphone system represents a new method for detecting acute infection, which would reduce the risk of virus transmission and could also be used to detect early treatment failure.”

Traditional virus monitoring methods for HIV are expensive, requiring the use of polymerase chain reaction (PCR). Shafiee and his colleagues sought to design an affordable, simple tool that makes HIV testing and monitoring possible for individuals in developing countries with less access to medical care.

Utilizing nanotechnology, a microchip, a cellphone and a 3D-printed phone attachment, the researchers created a platform that can detect the RNA nucleic acids of the virus from a single drop of blood. The device detects the amplified HIV nucleic acids through on-phone monitoring of the motion of DNA-engineered beads without using bulky or expensive equipment. The detection precision was evaluated for specificity and sensitivity.

Researchers found that the platform allowed the detection of HIV with 99.1 percent specificity and 94.6 percent sensitivity at a clinically relevant threshold value of 1,000 virus particles/ml, with results within one hour. Notably, the total material cost of the microchip, phone attachment and reagents was less than $5 per test.

“Health workers in developing countries could easily use these devices when they travel to perform HIV testing and monitoring. Because the test is so quick, critical decisions about the next medical step could be made right there,” said Shafiee. “This would eliminate the burden of trips to the medical clinic and provide individuals with a more efficient means for managing their HIV.”

“We could use this same technology as a rapid and low-cost diagnostic tool for other viruses and bacteria as well,” said lead author Mohamed Shehata Draz, ­­PhD, an instructor in the Division of Engineering in Medicine and Renal Division of Medicine at the Brigham.. “This platform could help a lot of people worldwide.”

Funding for this work was provided by the National Institute of Health under award numbers R01AI118502, R21HD092828, and P30ES000002; Harvard T.H. Chan School of Public Health, Harvard Center for Environmental Health through Harvard NIEHS Grant; and American Board of Obstetrics and Gynecology, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Society for Reproductive Endocrinology and Infertility through ASRMAward, and Harvard University Center for AIDS Research (CFAR) under award number 5P30AI060354–14.

Draz, MS et al. “DNA engineered micromotors powered by metal nanoparticles for motion based cellphone diagnostics” Nature Communications DOI: 10.1038/s41467-018-06727-8

FDA Approves First Drug Using the Recombinant Factor C Assay for Endotoxin Testing

Lonza announced today that the recombinant Factor C (rFC) Assay has been used for endotoxin testing of Eli Lilly’s Emgality™ (galcanezumab), the first drug approved by the U.S. Food and Drug Administration (FDA) to have been released using this method instead of traditional Limulus Amebocyte Lysate (LAL) - based  methods. Emgality™ is a monoclonal antibody drug treatment for the prevention of migraine in adults.

In 2003 Lonza launched the PyroGene™ recombinant Factor C Assay, the first endotoxin testing method to utilize a recombinant form of Factor C, the first component in the horseshoe-crab clotting cascade activated by the presence of endotoxins. As an animal-free method, the PyroGene™ Assay offers a more sustainable alternative to LAL-based tests that use the lysate obtained from horseshoe crab blood as their main ingredient.

“The recent FDA approval of Emgality™ marks a significant breakthrough in establishing the recombinant Factor C Assay as the non-animal method of choice for the identification of contaminating endotoxins in drug products,” said Lakiya Wimbish, Product Manager for Lonza’s PyroGene™ Recombinant Factor C Assay. “This development serves as an official confirmation that the recombinant Factor C method can be as accurate, sensitive and specific as LAL-based methods, while helping to secure the supply of natural resources.”

Allen Burgenson, Lonza’s Global Subject Matter Expert for Endotoxin Testing Solutions, said, “Lonza is the commercial innovator in bringing recombinant technology for endotoxin testing to market. This milestone accomplishment in advancing rFC technology will help to ensure the sustainability of the world’s horseshoe crab species. The three species of horseshoe crab found in Asia (Carcinoscorpius rotundicauda, Tachypleus tridentatus and Tachypleus gigas) are in serious decline due to overfishing, habitat loss and their use as a regional food. As these species become depleted due to a lack of regulatory oversight, countries such as China that use them to prepare Tachypleus Amebocyte Lysate (TAL) will look to the North American species, Limulus polyphemus, to fulfill their ever increasing needs in order to release non-pyrogenic pharmaceutical products to the market. Use of recombinant products, such as recombinant Factor C for endotoxin detection will greatly reduce the pressure on these species.”

Detecting E. coli Strains Using Molecular Electronics

Finding a fast and inexpensive way to detect specific strains of bacteria and viruses is critical to food safety, water quality, environmental protection and human health. However, current methods for detecting illness-causing strains of bacteria such as E. coli require either time-intensive biological cell cultures or DNA amplification approaches that rely on expensive laboratory equipment.

Now, Josh Hihath, an associate professor of electrical and computer engineering at the University of California, Davis, and colleagues at the University of Washington and TOBB University of Economics and Technology in Ankara, Turkey have adapted a molecular electronic device called a single-molecule break junction to detect RNA from strains of E. coli known for causing illness. The findings were published online in the journal Nature Nanotechnology.

“The reliable, efficient and inexpensive detection and identification of specific strains of microorganisms such as E. coli is a grand challenge in biology and the health sciences,” said Hihath. “Our technique could pave the way for rapid, straightforward detection of pathogens, antimicrobial resistant bacterial strains and biomarkers for cancer.”

Hihath and his team focused on E. coli since it is a common pathogen that could easily be found in the food supply, but might not cause illness in a benign form. The worst strain of E. coli, called E. coli O157:H7, produces a toxic substance called Shiga toxin that causes bloody diarrhea, kidney failure and even death.

Single-molecule break junction devices consist of two metal electrodes with atomically sharp interfaces that are brought into contact in a liquid solution of interest, such as a solution containing RNA sequences from E.coli. As the electrodes are brought into contact and pulled apart, an electrical bias is applied and the current is measured. This process is repeated hundreds or thousands of times to determine the conductance of a single molecule.

“One of the questions we asked is how small of a change in the sequence is needed to cause a meaningful change in the electrical conductance?” said Hihath. “The smallest thing we can change is a single-base, so we decided to see if a single-base change can be measured.”

By testing short sequences of RNA bound to DNA with chemical linkers, the team examined an E. coli sequence that would produce Shiga toxin. Their findings showed that changes in the electrical resistance of RNA due to a single-base change could be measured, which would allow them to see not only if a sequence was E.coli, but the specific strain of E.coli that produces Shiga toxin.

“A system that could selectively identify short sequences of DNA or RNA opens up new avenues for developing an electronic sensor platform for a wide range of applications,” he adds. “Eventually, we want to get to the point where we can extract RNA samples from real organisms and measure their conductance on a sensing platform.”

This work was supported in part by the National Science Foundation.

UCLA Engineers Invent Small, Inexpensive RNA Detector to Quickly Test for Infections

Today, most medical tests to detect bacteria or viruses in body fluids take hours or days to process. Now, researchers at the UCLA Samueli School of Engineering have invented a new technology to detect genetic material—such as that in microorganisms that cause disease—in a way that’s faster, cheaper, and does not require sophisticated equipment. A team led by Harold Monbouquette, professor of chemical and biomolecular engineering, and Jacob Schmidt, professor of bioengineering, patented their device, published the first description of the technology, and established a start-up company to begin developing prototypes of a commercial version of the detector.

“We’re working on developing a device that’s useful right at the point of care,” said Monbouquette, who is also the school’s associate dean for research and physical resources. “That means it can be easily run in a doctor’s office, clinic, or emergency room without samples being sent away to a lab.”
Nearly a decade ago, Monbouquette and Schmidt crossed paths—at a UCLA poster session—and discovered that they were both working on approaches to simplify the detection of nucleic acids, the DNA or RNA that defines cells’ and organisms’ identities. Rather than compete with each other, they teamed up and combined their ideas.

The new device relies on a 1-centimeter square glass slide that has an electric current flowing through it and is contacted by tiny plastic beads, each around 800 nanometers wide— less than one one-thousandth of a millimeter. Every plastic bead has molecules called peptide nucleic acid (PNA) coating its surface.

The PNAs are designed to bind specifically to whatever nucleic acid the test is detecting. If a doctor is interested in whether a patient has chlamydia, for instance, the PNA will only bind to a stretch of RNA that’s unique to chlamydia. If there’s even a tiny amount of that exact bit of RNA present, it will bind to the corresponding PNA and immediately interrupt the flow of the electric current, telling the doctor that the disease is present.

“It’s like a yes-or-no pregnancy test,” explained Monbouquette. “And that’s adequate for a lot of pathogens — you just want to know whether a patient is infected or not.”

In a recent paper, published in the journal Lab on a Chip in July, Monbouquette and Schmidt described the detection method’s high sensitivity— able to detect the equivalent of one bacterium in half a of a wine glass. Even when a mixture of bacteria was tested, the chip could detect the presence of Escherichia coli when there were 1 million-times more RNA molecules from another bacterium, Pseudomonas putida. Moreover, the technique had no false positive results during the initial experiments.

The researchers think the technology—once it’s adapted to a form that can be mass-produced—will give doctors the ability to run faster labs to diagnose a variety of infections.

“There are a lot of diseases where the doctor takes a sample, sends it off to the lab, and doesn’t get results for days,” said Schmidt. “We can do it in 15 minutes or less, which means you can sit in the waiting room, wait for an answer, and potentially start getting treated before you ever leave the doctor’s office.”

He envisions a small toaster-sized device in which different cartridges— each containing the glass slides for a specific pathogen— can be inserted depending on what test needs to be run. It’s hard to predict the cost since a manufacturable prototype hasn’t been developed yet, but Schmidt said each test will be “easily under $50.”

With that kind of application and price point in mind, Monbouquette and Schmidt have founded Electronucleics, a company that will oversee further development of the nucleic acid detection technology. Their first goal is to streamline the processing needed for samples to be run on the machine—in the lab, they’ve been using filters, pipets, test tubes and a handful of reagents to process samples before injecting them into the detector. Next, they will work with an outside firm to develop a planned prototype featuring push-button simplicity.

They plan to first optimize the technology for use in detecting gonorrhea and chlamydia infections—there’s an unmet need for rapid diagnosis of these sexually transmitted diseases, the researchers said. But they envision other applications in the future, including the diagnosis of respiratory illnesses and flu, or the detection of pathogens in food and water.