Focus Feature: COVID-19
Pushing for a SARS-CoV-2 vaccine
The race is on to develop a vaccine as the pandemic continues
By Jeffrey Bouley
Vaccination is a proven way to put many infectious diseases in their place, and has been instrumental in not only beating back such maladies as polio and measles, but also keeping seasonal influenza outbreaks in check. One challenge, of course, has been in staying ahead of viral mutations in the coronaviruses that cause illnesses like influenza.
But the challenge faced in tackling the flu each year is ramped up several levels with the novel coronavirus SARS-CoV-2 that causes COVID-19, which has been sweeping across the globe. We haven’t seen this virus in humans before, our bodies aren’t ready for it and we are only just starting to understand the mechanisms of the virus and the full etiology of the disease.
Many companies are rising to the challenge, pushing to try to get a vaccine ready within a year or so because of the highly contagious nature of SARS-CoV-2 and the much higher mortality rate of COVID-19 compared to seasonal flu.
While we will get to some of those specific efforts shortly, it is worth noting that public and private entities are banding together to set guidelines and provide assistance in these efforts.
Global regulators convene
One such effort began with a March 18 teleconference of global regulators convened jointly by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) under the auspices of the International Coalition of Medicines Regulatory Authorities (ICMRA). In that conference, they discussed regulatory considerations related to the development of SARS-CoV-2 vaccine candidates and preclinical data requirements to support proceeding to first-in-human (FIH) clinical trials.
The two key topics addressed by regulators in the meeting were discussion of the preclinical data required to support proceeding to FIH clinical trials, and the need to address the theoretical risk for SARS-CoV-2 vaccine-induced disease enhancement prior to proceeding to FIH clinical trials. (For more on the second topic, see the sidebar “SARS-CoV-2 vaccine disease enhancement risks” right after this article.)
Looking at the preclinical aspect of vaccine development to support FIH trials, the participants considered the following:
- They acknowledged that the extent of preclinical data to support proceeding to FIH clinical trials depends on the vaccine construct, the supportive data available for the construct and data from closely related products
- They noted that opportunities to leverage knowledge accumulated with platform technology should be considered to accelerate the development of a SARS-CoV-2 vaccine manufactured using the same platform
- To the previous point, if a platform technology utilized to manufacture a licensed vaccine or other investigational vaccines is well characterized, for example, it is possible to use toxicology data (e.g., data from repeat dose toxicity studies, biodistribution studies) and clinical data accrued with other products using the same platform to support FIH clinical trials for a SARS-CoV-2 vaccine candidate
- They also noted that the vaccine manufacturer should provide a rationale supported by data to justify why certain preclinical studies, such as toxicity studies, would not need to be conducted prior to proceeding to FIH clinical trials
- Chemistry manufacturing and controls characterization should be adequate to support the safety of the SARS-CoV-2 vaccine construct prior to proceeding to FIH clinical trials
- For all SARS-CoV-2 vaccine candidates, it is necessary to obtain data in animals and to characterize the immune response induced by a SARS-CoV-2 vaccine candidate
- It is not required to demonstrate the efficacy of the SARS-CoV-2 vaccine candidate in animal challenge models prior to proceeding to FIH clinical trials.
“This first global regulators discussion was a critically important exchange of information and views. The FDA and the EMA intend to convene additional meetings with other global regulators to enable sharing of data from upcoming clinical trials to help ensure global preparedness and promote regulatory convergence, with the goal of streamlining global SARS-CoV-2 vaccine development,” said Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.
Even before the global teleconference, the EMA noted that it had “activated its plan for managing emerging health threats,” according to Guido Rasi, the agency’s executive director, who added, “The new coronavirus has been declared a public health emergency of international concern by the World Health Organization, and we are drawing on the strong expertise of the European medicines network to provide fast-track scientific advice and give prompt feedback on any proposed medicine developments.”
The EMA also noted that it is “surveying the landscape” for potential antivirals and vaccines to treat or prevent novel coronavirus infections, and that it will collaborate and exchange information with European Union public health authorities, notably the European Commission, the Health Security Committee and the European Centre for Disease Prevention and Control, the World Health Organization and other international regulators, in particular through the ICMRA.
“Vaccine development is still at an early stage. There are no existing vaccines that could be repurposed to work against the new virus,” the EMA stated. “Timelines for vaccine development are difficult to predict at this point, but it is currently estimated that the first clinical trials will not start before April/May 2020. This means that it will take several months before candidate vaccines are ready for larger clinical studies. Once there is sufficient information available, EMA is ready to assess any applications for marketing authorization within the shortest possible timelines.”
Other help on the way
On the same day that global regulators convened, the U.S. Pharmacopeia (USP) announced that it would provide free technical assistance to developers of medical treatments such as antiviral drugs and vaccines that can support the public health response to the COVID-19 pandemic. USP is making its scientific teams available to help developers ensure the quality of their materials as they scale up manufacturing to bring products into the clinical environment, as well as to design tests that ensure quality of materials.
Consortia are also coming onto the scene, with Themis announcing March 19 that it would join a consortium with Institut Pasteur and University of Pittsburgh—with funding support from the Coalition for Epidemic Preparedness Innovations (CEPI)—to rapidly develop a COVID-19 vaccine candidate based on the versatile measles virus vector technology licensed exclusively to Themis by Institut Pasteur in Paris.
At the end of March, Cobra Biologics, an international contract development and manufacturing organization for biologics and pharmaceuticals, announced it is working as part of a consortium led by the Jenner Institute at Oxford University to rapidly develop, scale up and produce a potential adenoviral vaccine candidate, ChAdOx1 nCov-19 (ChAdOx1), for fast-tracked clinical trials for COVID-19. ChAdOx1 is one of five frontrunner vaccines in development around the world, and could end up being the United Kingdom’s first COVID-19 vaccine. The ChAdOx1 consortium also includes the University of Oxford Clinical Biomanufacturing Facility, the Vaccines Manufacturing and Innovation Centre (VMIC), Advent Srl, Pall Life Sciences and Halix BV.
Developed at the Jenner Institute, ChAdOx1 is said by its backers to be one of the most promising vaccine technologies for COVID-19, as it can reportedly generate a strong immune response from one dose. Data so far suggest it might be able to be given safely to vulnerable members of the public, including children, the elderly and those with a pre-existing condition such as diabetes.
Additional efforts in the industry
Codagenix Inc., a clinical-stage biotechnology company developing prophylactic vaccines and oncolytic virus therapies, announced back in February that it had begun a collaboration with the Serum Institute of India to rapidly co-develop a live-attenuated vaccine against the emergent coronavirus. The company uses “viral deoptimization” to synthesize rationally designed, live-attenuated vaccines, and it says that its technology allows for the rapid generation of multiple vaccine candidates against emerging viruses, starting with only the digital sequence of the viral genome.
Also in February, French drugmaker Sanofi teamed up with the Biomedical Advanced Research and Development Authority in the United States to develop a vaccine against the new coronavirus, and Sanofi said that it might have a candidate ready for clinical trials within a year.
In mid-March, Pfizer Inc. and BioNTech SE agreed to a letter of intent regarding the co-development and distribution (excluding China) of a potential mRNA-based coronavirus vaccine aimed at preventing COVID-19 infection. The collaboration aims to accelerate development of BioNTech’s potential first-in-class COVID-19 mRNA vaccine program, BNT162, which is expected to enter clinical testing by the end of April 2020.
This builds on a research and development collaboration into which Pfizer and BioNTech entered in 2018 to develop mRNA-based vaccines for prevention of influenza.
“We are proud that our ongoing, successful relationship with BioNTech gives our companies the resiliency to mobilize our collective resources with extraordinary speed in the face of this worldwide challenge,” said Mikael Dolsten, chief scientific officer at Pfizer.
Meanwhile, Luina Bio and Griffith University said they are combining Luina Bio’s leadership position in the Australian biopharmaceutical industry with the strength of Griffith University’s rapid response technology in the hopes of making a significant contribution toward a COVID-19 vaccine.
Also in Australia, Murdoch Children’s Research Institute (MCRI) has announced its infectious disease researchers are preparing to roll-out a multicenter randomized controlled clinical trial of the BCG vaccine—which is currently used primarily against tubercolosis—against the novel coronavirus.
In yet another Australia-based effort, the Melbourne-based factory of the Commonwealth Scientific and Industrial Research Organization (CSIRO) began production of a test dose for a potential vaccine at the end of February.
As noted by Kajal Jaddoo, a healthcare analyst at analyst firm GlobalData, regarding the CSIRO work, “Researchers from the University of Queensland developed this test vaccine in six weeks using world-first molecular clamp technology. Animal testing of the vaccine is set to begin.
“While the development of vaccines is time-consuming, this first test dose is in production, which shows incredible progress by the researchers. Using a DNA blueprint of COVID-19 by Chinese scientists, the researchers identified a section of the virus to target, specifically a spike protein. The molecular clamp technology holds and changes the shape of the spike protein to allow the human immune system to recognize and kill it.”
Sartorius, for its part, noted that it is supporting CanSino Biologics Inc. and a research team at the Institute of Bioengineering at the Academy of Military Medical Sciences in China in their development of a vaccine candidate against SARS-CoV-2, which is entering clinical trials. For their work, CanSinoBIO and the Institute of Bioengineering used Sartorius’ BIOSTAT STR single-use bioreactor system for the upstream preparation of the recombinant vaccine. Sartorius says its technology has been proven useful before in vaccine manufacturing because it offers rapid scalability and flexibility to adapt to fluctuating demand.
In addition to its consortium work noted earlier, Cobra Biologics entered into a collaboration with the Karolinska Institutet, bolstered by €3 million in emergency funding from Horizon 2020, for research and development and Phase 1 clinical trial testing of a DNA vaccine against COVID-19.
Also, Johnson & Johnson plans to begin human testing of its experimental vaccine for SARS-CoV-2 by September, and it could be ready for emergency use authorization by early next year.
By no means is this list exhaustive, and we will keep you posted as we learn of additional vaccine-related efforts against the novel coronavirus.
SARS-CoV-2 vaccine disease enhancement risks
Global regulators’ discussion of the theoretical risk for SARS-CoV-2 vaccine-induced disease enhancement prior to proceeding to first-in-human (FIH) clinical trials covered several issues, among them the following:
- There is urgency of proceeding to FIH trials with SARS-CoV-2 vaccine candidate, but risk mitigation strategies remain important so that human subjects enrolled in clinical trials would not need to be exposed to unreasonable risk
- The potential for vaccine-induced disease enhancement is a special circumstance that needs to be evaluated according to available science, which may include the use of relevant animal models currently in development
- Even though there are limitations in the current knowledge and understanding of risk of enhancement of disease and the value of these models in predicting likelihood of occurrence in humans, studies in animal models are considered important to understand the potential for vaccine-induced disease enhancement with SARS-CoV-2 vaccine candidates
- Because of limited availability of non-human primates, requiring such studies with every SARS-CoV-2 vaccine candidate prior to FIH trials is not possible and would significantly delay clinical vaccine development
- Some vaccine constructs for which there is adequate information and support from the knowledge around the immune response elicited may be permitted to proceed to FIH trials without first completing animal studies, but for some vaccines, preclinical data (e.g. postvaccination challenge data from animal models, immunopathology studies in animal models, etc.) may be required prior to advancing to FIH clinical trials
- In the event that FIH clinical trials are permitted to proceed in the absence of studies in animals, such animal studies are, in general, expected to be conducted in parallel with FIH trials so that these data are available prior to enrolling large numbers of human subjects into Phase 2 and 3 clinical trials.
The regulators also expressed the need for developing mechanisms that would allow sharing of data from animal models and clinical trials to alert the global regulatory community regarding the outcomes of trials in an ongoing and timely manner.
Researchers converge on COVID-19
While the world waits for vaccines against the new coronavirus, scientists pursue therapeutics for the illness it causes
By Jeffrey Bouley
Given the suddenness with which the SARS-CoV-2 virus struck and the speed with which people have contracted COVID-19 and co-morbidities of the disease, efforts to find cures for infection are at a similar fever pitch as those to create a vaccine.
Unsurprisingly, there is significant work being done to explore existing drugs for potential efficacy against COVID-19. As noted by the European Medicines Agency on March 31, among the potential treatments for COVID-19 that are undergoing clinical trials already to assess their impact on the disease are:
- Remdesivir (investigational)
- Lopinavir/ritonavir (currently authorized as an anti-HIV medicine)
- Chloroquine and hydroxychloroquine (currently used as treatments against malaria and certain autoimmune diseases such as rheumatoid arthritis)
- Systemic interferons, in particular interferon beta (currently authorized to treat diseases such as multiple sclerosis)
- Monoclonal antibodies with activity against components of the immune system.
Novartis, for its part, announced at the end of March that it is donating 20,000 doses of hydroxychloroquine to the University of Washington for a COVID-19 post-exposure prophylaxis clinical trial. Sandoz, the company’s generics and biosimilars division, is facilitating the donation. Earlier in the month, Novartis announced that it would donate up to 130 million doses of generic hydroxychloroquine to support the global COVID-19 pandemic response.
CEL-SCI Corp. recently signed a collaboration agreement with the University of Georgia’s Center for Vaccines and Immunology to develop the LEAPS COVID-19 immunotherapy. CEL-SCI’s immunotherapy candidate aims to treat patients at highest risk of dying from COVID-19.
The collaboration will begin with preclinical studies based on experiments that had already been conducted with the LEAPS (Ligand Epitope Antigen Presentation System) immunotherapy in collaboration with the National Institutes for Allergies and Infectious Diseases against another respiratory virus, H1N1—the virus involved in the 2009 H1N1 flu pandemic. Those successful studies reportedly demonstrated that LEAPS peptides, given after virus infection has occurred, reduced morbidity and mortality in mice infected with H1N1.
It is possible that a LEAPS coronavirus SARS-CoV-2 immunotherapy could reduce or arrest the progression of the SARS-CoV-2 virus infection and prevent tissue damage from inflammation resulting from lung infection by the virus. By stimulating the correct immune responses to the COVID-19-causing virus without producing unwanted inflammatory responses associated with lung tissue damage, LEAPS immunotherapy may be particularly beneficial in those patients who are at highest risk of dying from COVID-19.
“We are eager to commence these studies, which if successful, may lead to clinical trials in humans to address the immediate and critical need to treat COVID-19 in the most vulnerable patients. We are very pleased and honored to partner with Dr. Ted M. Ross and his team and the University of Georgia Center for Vaccines and Immunology,” said CEL-SCI CEO Geert Kersten.
Added Ross: “LEAPS has the potential to be a powerful tool against SARS-CoV-2, the causative agent of COVID-19, based on its dual antiviral and anti-inflammatory properties. Combining the prior preclinical data of LEAPS against H1N1 with our advancing knowledge of COVID-19, we aim to rapidly evaluate this technology’s potential to meet the urgent need to treat patients at greatest risk of dying from this global pandemic. The University of Georgia’s biocontainment labs at the Center for Vaccines and Immunology are ideally suited for these studies, and will serve as critical assets in this collaboration with CEL-SCI.”
Previous studies indicated that LEAPS immunogens could prevent lethal infection by herpes simplex virus (HSV) and influenza A (H1N1) and stop the inflammatory disease progression of rheumatoid arthritis in animal models. LEAPS peptides against HSV demonstrated that the T cell response was sufficient to prevent viral disease, and if there was residual virus production, an antiviral antibody was generated to further control the spread of the virus.
The proposed LEAPS peptides for the COVID-19 study are directed toward antigens within the NP protein of SARS-Cov-2 virus that elicit cytolytic T cell responses. Unlike the viral glycoprotein “spike” antigens that are important for antibody-based vaccines, these NP-antigens are said to be less variable between viral strains and less likely to change in response to antibodies elicited by prior infection or other vaccines.
Speaking of antibodies, late March saw Vir Biotechnology sign a deal with Xencor related to an antibody-extending technology. Specifically, Vir has in-licensed non-exclusive rights to Xencor’s Xtend Fc technology that can extend the half-lives of novel antibodies it is investigating for the potential treatment of COVID-19.
One of the problems with protein-oriented therapeutics is the fact that they can degrade in circulation too quickly. However, Xencor’s technology increases binding affinity to a receptor called FcRn which is present inside lysosomes in epithelial cells lining blood vessels, thus “rescuing” antibodies from such degradation.
Tiziana Life Sciences plc, a biotechnology company focused on inflammatory and autoimmune diseases, says that it is expediting development of TZLS-501, a novel, fully human anti-interleukin-6 receptor (anti-IL6R) monoclonal antibody (mAb) for treatment of patients infected with coronavirus COVID-19. The company entered into a worldwide license for composition of matter of TZLS-501 with Novimmune, SA, a Swiss biotechnology company, in 2017.
As Tiziana notes, certain patients infected with coronavirus COVID-19 may develop an uncontrolled immune response (sometimes called a cytokine storm), resulting in severe damage to lung tissue which could lead to respiratory failure. Early clinical studies conducted by physicians and other researchers in China suggest that anti-IL6R mAbs may be used in clinical practice for treatment of COVID-19.
Tiziana’s anti-IL-6R mAb binds to both the membrane-bound and soluble forms of IL-6R and rapidly depletes circulating levels of IL-6 in the blood, according to the company. Excessive production of IL-6 is regarded as a key driver of chronic inflammation, and is believed to be associated with severe lung damage observed with COVID-19 infections and acute respiratory illness.
“We believe that the features of TZLS-501—consisting of its dual mechanism of action to inhibit signaling by the membrane-bound and soluble IL-6 receptors, along with rapid depletion of circulating IL-6 cytokine, a major cause of lung damage—provide TZLS-501 with distinct advantages for treatment of COVID-19 over other anti-IL-6R mAbs, such as Actemra and Kevzara, for treatment of COVID-19,” said Dr. Kunwar Shailubhai, CEO and chief scientific officer of Tiziana. “The recent decision by researchers in China to add Actemra to treatment guidelines for coronavirus patients with serious lung damage confirms the utility of anti-IL6R mAb. We are excited to move forward with our clinical development plan to expedite evaluation in patients as soon as possible.”
Looking more broadly at potential antibodies, Carterra Inc. was selected by the La Jolla Institute of Immunology (LJI) to provide antibody screening and characterization for the Coronavirus Immunotherapy Consortium (CoVIC), which is funded in part by the Bill and Melinda Gates Foundation.
LJI said it would use Carterra’s proprietary LSA platform to screen hundreds of antibodies in just a few days, allowing CoVIC to move therapeutic candidates to the clinic as early as this summer.
Headquartered at LJI, CoVIC will serve as a clearinghouse to understand which antibodies are most effective against the novel coronavirus SARS-CoV-2 and to accelerate the research pipeline to provide immunotherapeutics in order to protect vulnerable individuals from severe manifestations of COVID-19 in all parts of the world, including low-resource settings.
This effort is being funded as part of the COVID-19 Therapeutics Accelerator launched in early March by the Gates Foundation, Wellcome and Mastercard. The Accelerator aims to provide “fast and flexible funding” at key stages of the development process to de-risk the pathway for drugs and biologics to prevent and treat COVID-19.
“We are thrilled that Carterra will provide full antibody characterization data using affinity measurements and, potentially more importantly, ultra-high resolution information of the epitopes,” commented Dr. Erica Ollmann Saphire, a professor in LJI’s Center for Infectious Disease and Vaccine Research. “Knowing how well these antibodies bind to the target is important, but understanding their mechanism of action and how different antibodies can complement each other will determine what ends up in the clinic.”
As Carterra and LJI note, traditional antibody discovery requires a primary screen of ever-expanding antibody libraries. Only a small group of candidate antibodies are then characterized on traditional, low-throughput, low-resolution biosensor tools which provide real-time readout of the binding profile. This workflow runs the risk that potential drug candidates could be missed, or that the process of candidate selection could be exceedingly long.
According to Carterra, its LSA technology “is turning that model on its head” by enabling the high-resolution analysis of entire libraries, combining screening and characterization into one step, thereby minimizing the risk of missing a potent therapeutic candidate and reportedly condensing months of work into days.
Diagnostic efforts progress rapidly
LGC Diagnostics’ SeraCare Life Sciences announced in March that with the rapid global spread of the SARS-CoV-2 virus and the urgent need for reliable diagnostic solutions, it is expanding production of its novel COVID-19 reference materials to include high-titer stocks that serve as a valuable tool for diagnostic manufacturers.
“As a leading provider to the in-vitro diagnostic industry, we are keenly aware of the important role that reliable reference materials play in the development of accurate diagnostic tests,” said Michael Sweatt, executive vice president and general manager at LGC Diagnostics. “Offering our AccuPlex COVID-19 solution in a high-titer format enables diagnostic manufacturers to accelerate development efforts through use of concentrated, lot-specific reference material to complete their assay validation activities.”
Meanwhile, Mologic Ltd, a developer of lateral flow and rapid diagnostic technologies, announced in March that it had been awarded about £1 million by the Wellcome Trust and the Department for International Development as part of the U.K. government’s £46-million international coronavirus prevention and research funding package.
The funding will be used by Mologic and global partners to develop a point-of-need diagnostic test for the virus, in addition to supporting the company’s efforts to initiate research for novel vaccine candidates.
Mologic says it will build on its experience developing a rapid test kit for Ebola to create a new handheld diagnostics device to detect COVID-19. This will reportedly allow health officials to test for the virus at home or in the community, providing results in 10 minutes, without the need for electricity or a laboratory. The company is working in partnership with the Institut Pasteur de Dakar to validate and manufacture the COVID-19 test at a new manufacturing site, DiaTropix, in Senegal.
“As seen with the COVID-19 outbreak, viruses can quickly transmit between populations; however, our knowledge to tackle this threat has also grown exponentially,” noted Prof. Paul Davis, co-founder and chief scientific officer of Mologic. “For rapid epidemic preparedness and response, we need to develop a platform that is readily modified according to a novel pathogen, as we are demonstrating through our accelerated programs for Ebola and COVID-19.”
By late March, Mologic had begun early validation of its COVID-19 point-of-need diagnostic tests with the Liverpool School of Tropical Medicine and St Georges’ University London.
Also looking to speed things up for point-of-care diagnostics, Heat Biologics Inc., a clinical-stage biopharmaceutical company, has entered into a collaboration with the University of Miami to develop a proprietary COVID-19 test.
The test would require a simple pharyngeal throat swab to deliver on-the-spot results on a paper strip in under 30 minutes. In contrast, current tests for COVID-19 usually rely on the use of expensive thermal-cyclers, with results in five to six hours, or require blood draws to detect antibodies indicative of previous exposure. Preliminary research suggests the new test is specific to the novel coronavirus, with no cross-reaction to previous coronavirus subtypes. The test is designed to enable cost-effective manufacturing amenable for mass production and deployment around the world.
“Our lab has tremendous experience developing accurate and easily usable tests for infectious diseases such as HPV and Zika,” said Dr. Sylvia Daunert, chair of biochemistry and molecular biology at the University of Miami Miller School of Medicine. “Unlike tests that detect antibodies (IgG and IgM method), which can take weeks to manifest, our test is being developed to utilize molecular recognition and amplification of the target virus. This should allow for much earlier detection—within a couple days of exposure—providing critical and time-sensitive information to help curb the spread of the disease.”
And in one last example of recent diagnostics work around the novel coronavirus, March 19 brought news from Bio-Rad Laboratories Inc. that in two studies published this month, ahead of peer review, researchers in China reported that the company’s QX200 Droplet Digital PCR (ddPCR) System showed superior sensitivity and precision for clinical detection of SARS-CoV-2 compared to existing test methods that are performed using qPCR.
In the first study, clinicians in Wuhan, China, observed that a subset of infected individuals who tested negative for COVID-19 using qPCR tested positive using ddPCR. The findings suggest that ddPCR can reduce false-negative results of COVID-19 without any increase to false-positive results, and could be a powerful complement to the current standard of testing.
The second study, led by the National Institute of Metrology and provincial disease control agencies in China, also concluded that Droplet Digital PCR significantly improves diagnostic detection accuracy of SARS-CoV-2 from 28.2 percent to 87.4 percent, thereby reducing false negatives. Furthermore, they found that Droplet Digital PCR is more sensitive and suitable for low virus load specimens from patients under isolation and observation even without any clinical symptoms.
“Bio-Rad is working to make ddPCR-based tests available for COVID-19 detection and is partnering with Biodesix in Colorado to bring an Emergency Use Authorization test online,” stated Norman Schwartz, Bio-Rad’s president and CEO. “By more quickly identifying those who test positive for the virus, individuals can be quarantined and receive treatment as quickly as possible, helping to contain the spread of COVID-19.”
FDA continues to formulate diagnostic guidance
As of late March, the U.S. Food and Drug Administration was still taking a piecemeal approach to guidelines for those developing tests for SARS-CoV-2 infection and COVID-19. However, on March 25 the agency did take another step forward by summarizing and organizing four pathways for such tests.
The pathway it is currently calling Policy A is designed for CLIA-certified labs that wish to launch validated SARS-CoV-2 tests and specifies that labs are permitted to begin using tests on patient samples as soon as they are validated internally, if they have notified FDA and subsequently file an EUA application within 15 days.
Policy B is intended to allow individual states to authorize tests within their jurisdictions that will be run in high-complexity CLIA labs. Under this pathway, tests can be used on patients as soon as they are validated and the FDA is notified, and a subsequent EUA is not required.
Policy C is aimed a commercial manufacturers of COVID-19 tests and says that a manufacturer can launch its test and platform as soon as it is validated, provided it has notified FDA and will submit an EUA application within 15 business days.
All three of those pathways apply to molecular, antigen and antibody tests.
The fourth pathway, Policy D, applies only to antibody-based serology tests. According to current FDA policies, such tests—regardless of whether they come from a commercial manufacturer or a CLIA lab—do not need to submit an EUA application at all.