Coronavirus COVID-19 (SARS-CoV-2) Detection, Characterization, Vaccine and Therapy Production

Immunology

Patient immune response to COVID-19 infection is variable and may contribute to negative clinical outcomes. A hyperinflammatory response can lead to cytokine storm syndrome (CSS), with significant impact on disease severity. Cytokine reagents and MILLIPLEX^® multiplex cytokine/chemokine detection panels provide comprehensive understanding of the inflammatory response to viral infection for both human and non-human primate samples. Our MILLIPLEX^® solutions have expanded to include kits to detect antibodies against SARS-CoV-2 antigens in human serum or plasma samples. These immunoassay kits are for research use only in critical efforts such as epidemiology and population research studies.

• MILLIPLEX^® MAP Human cytokine panels
• MILLIPLEX^® kits for SARS-CoV-2 IgG, IgA, IgM antibody detection
• Human and mouse cytokines for viral response and inflammation research
  

 MILLIPLEX^® MAP Human cytokine panels

Patient immune response to COVID-19 infection is variable and may contribute to negative clinical outcomes. Hyperinflammatory response can lead to cytokine storm syndrome (CSS), with significant impact on disease severity. Cytokines and MILLIPLEX^® multiplex cytokine/chemokine detection panels provide comprehensive understanding of the inflammatory response for both human and non-human primate samples.

 MILLIPLEX^® research kits for SARS-CoV-2 antibody detection

These MILLIPLEX^® kits are for the detection of antibodies against SARS-CoV-2 antigens in human serum or plasma samples. These immunoassay kits are for research use only, and facilitate COVID-19 research efforts for critical vaccine development, epidemiology, and population research studies.

 Human and mouse cytokines for viral response and inflammation research

The immune response to SARS-CoV-2 infection can lead to significant COVID-19 patient morbidity and mortality. Our diverse collection of human and nonhuman cytokines may help to elucidate patient Inflammatory and anti-inflammatory compensation in research models.

From early phase development, to large scale production, Vaccine manufacturers are concerned with balancing speed to market and cost containment, while maintaining product safety. Our process development engineers, regulatory experts, and comprehensive portfolio of products and services can help you meet your process goals and many process challenges, such as increasing process efficiency and product recovery, achieving higher product yield, and ensuring process safety and reproducibility of multi-strains products.

• Upstream
  
• Downstream
  
• Formulation
  
• Biosafety Testing Services
  
• Cell Line Characterization
  
• Quality Control and Environmental Monitoring
  
• Screening
  
• Development and Manufacturing Services
  
• Analytical Methods for Nucleic Acid Vaccine

Upstream

Our upstream portfolio includes single-use bioreactors, cell culture media, media supplements, critical raw materials, buffers, mixers, and a full range of filtration technologies to prevent microbial contamination and ensure your process meets yield and productivity targets.

Downstream

From scale-up to full-scale production, we offer a range of filtration technologies, buffers, CIP solutions, stainless and single-use systems, integrated technologies as well as validation services. Coupled with our in-house application experts who have decades of know-how, we can help you tackle any downstream processing challenge.

Formulation

Our extensive portfolio of process chemicals, excipients and lipids are designed for demanding, time-sensitive applications including vaccine formulation.

We offer innovative lipid-based drug delivery excipients, such as Squalene and Synthetic Cholesterol, with superior characteristics enabling you to simplify and streamline formulation processes. You can also take advantage of our customized lipids manufacturing to create a tailored approach for your API.

To meet the unprecedented demand created by the global development of COVID-19 vaccines, we have increased production capacities and can supply GMP material in quantities ranging from grams to tons.

Many of the process chemicals in our broad portfolio are part of our Emprove^® Program, which provides comprehensive regulatory documentation to simplify and accelerate regulatory filings.

• Learn more about our lipid-based drug delivery excipients
• Explore our lipids customized manufacturing capabilities
• Discover our portfolio of excipients for biomolecule formulation including our dedicated stabilizers

Biosafety Testing Services

We’re here to partner with you. Our testing facilities are operating and we’re actively engaging the biopharma community to prioritize biosafety testing during this health crisis. Just as we did during Zika, SARS, and Ebola outbreaks, we’re here to support vaccine and therapeutic developers and manufacturers to prioritize therapies. Contact our commercial teams to discuss your needs.

Learn more about our BioReliance^® Viral Clearance Studies.

Learn more about our BioReliance^® Bulk Harvest Lot Release Testing and BioReliance^® Comprehensive Lot Release Testing.

Learn more about our BioReliance^® Product Characterization Services.

Learn more about our BioReliance^® Cell Banking and Biorepository Services.

BioReliance^® Vaccine Bulk Harvest Testing

Biosafety testing of vaccine bulk harvest and control cells involves a range of tests to demonstrate freedom from adventitious agents (bulk harvest and control cells) and to confirm identity of the vaccine material (bulk harvest). The choice of tests should be based on a viral safety risk assessment as well as relevant regulations and guidance documents and will typically address the following key areas:

• Detection and identification of vaccine gene of interest
  
• Vaccine virus titre
  
• Sterility, Mycoplasma and Mycobacterium
  
• Neutralization of vaccine virus for cell and in vivo based adventitious virus tests
  
• Adventitious viruses

Tests can be performed using a range of methods, from traditional cultivation and sequencing assays to state-of-the art rapid methods employing novel molecular methods such as Next Generation Sequencing and degenerate PCR. Contact info@bioreliance.com to discuss your needs.

Cell Line Characterization

Learn more about our BioReliance^® Cell Line Characterization Services.

Learn more about our BioReliance^® Product Characterization Services.

Learn more about our BioReliance^® Viral Clearance Studies.

Learn more about our BioReliance^® Bulk Harvest Lot Release Testing  and BioReliance^® Comprehensive Lot Release Testing.

Learn more about our BioReliance^® Next Generation Sequencing (NGS).

Learn more about our BioReliance^® Blazar Rapid Molecular Detection Platform.

BioReliance^® Vaccine Efficacy Studies

Vaccine efficacy studies are performed to establish the ability of the vaccine to induce a protective response. These should be performed before the first in man clinical studies. These studies normally require immunisation into a suitable model system and demonstrating an immune response using firstly ELISA methods and then demonstrating the immune response is protective by using viral neutralization methods. These methods can then be modified and used as potency release assays for releasing each batch of clinical product, as well as a stability indicating method for stability studies. Contact info@bioreliance.com to discuss your needs.

Quality Control and Environmental Monitoring

Effective quality assurance, constant quality control and accurate results are key to manufacturing safe therapies. Our complete solutions for microbial detection and sterility assurance help you meet the highest quality standards and regulatory demands.

Many organizations are experiencing increased production demands as a result of the COVID-19 pandemic situation. The Milliflex Quantum^® system is a rapid microbial detection technology that can help reduce routine testing times significantly, providing results in 1/3 the time of traditional microbiology methods. This valuable time savings can be leveraged to facilitate early release of urgently needed supplies to their intended destination (medial, hospitals, labs).

Screening

Screening can directly identify drug targets for treating COVID via anti-virals and also aid in identification of targets within producer cell lines that can then be engineered to more efficiently produce virus/viral particle vaccines at a larger scale. Explore our Functional Genomics CRISPR and RNAi Libraries.

Development and Manufacturing Services

World-class process development and manufacturing for virus-based therapeutic products. From small scale toxicology and Phase I material to commercial-scale manufacturing and fill finish, our flexible facilities and expert staff are leaders in viral product manufacturing. Learn more about our BioReliance^® Viral and Gene Therapy Manufacturing.

With extensive experience in producing customized cell lines for enhancing viral vaccine production, our cell engineering services enable you to produce higher levels of vaccine titer and scalable production cell lines. We will work with the parental cell line of your choice to generate your desired modifications.

Analytical Methods for Nucleic Acid Vaccine

Nucleic Acid Vaccines - Product and process related impurities

A variety of analytical methods are available to assess product purity. Typically, these will include a combination of orthogonal separation techniques, such as chromatography (RP-HPLC, SEC, IEX) and electrophoresis (CE-SDS). Additional assays can be employed to test for impurities specific to the particular product or process. For example, residual enzymes and DNA in RNA based products. Contact info@bioreliance.com to discuss your needs.

Therapy Production

Knowing what to expect and who and where to go for guidance can provide confidence you’re on the right track and accelerate you on the right path. From bench to full-scale production, we offer a full range of raw materials, tools, services, and technologies, from off-the-shelf to customizable, to accelerate development, optimization, and scale-up of your process. Our in-house experts have decades of bioprocessing experience and will collaborate with you to tackle any development and processing challenges, as well as provide quality testing services.

• Small Molecule Therapeutics
  
• Analysis of Antivirals and other therapeutic drug candidates
  
• Assay and Impurity Profiling Methods
• Plasma-Derived Therapies
  
• Monoclonal Antibodies
  
• Quality Control and Environmental Monitoring
  
• Biosafety Testing Services
  
• Novel Modalities
  
• Virus & Viral-Like Therapies

Small Molecule Therapeutics

Classical Pharmaceutical Formulation & Manufacturing

Finding a robust formulation, complying with regulatory requirements, and adhering to quality standards are all top priorities when manufacturing an anti-viral or other small molecule drug.

Based on our expertise in this industry, we understand your challenges in development and manufacturing of small molecule pharmaceuticals and formulation and can support you with products and services. Find out more about our portfolio and access relevant technical resources.

Comprehensive End to End Solutions for Genotoxicity Assessment

BioReliance^® offers genetic toxicology services for the detection of toxic, mutagenic, clastogenic and morphological transforming activity in a number of well-characterized test systems. Our scientific staff and state-of-the-art facilities provide the most current and comprehensive genetic toxicology resources available anywhere.

Analysis of Antivirals and other therapeutic drug candidates

Therapeutic drugs must be tested – from drug development to Quality Control (QC) of the active pharmaceutical ingredient as well as the final formulation.

Our offering comprises products for Analysis such as: Standards and Reference Materials, HPLC and UHPLC Columns and accessories, TLC products, GC, Solvents, Buffers and Reagents, Sample preparation, Filtration, Water Purification Solutions and many more.

Various drugs¹ are currently under investigation as to whether they are effective treatment for COVID-19, including Lopinavir, Ritonavir², Chloroquine³, and Fingolimod⁴ for which we can offer the CRMs and the primary compendial standards.

Assay and Impurity Profiling Methods

Several HPLC methods (Assay and Impurity Profiling methods) have been developed to assess, control and test the quality of COVID-19  drug candidates. The published methods follow either specific Ph EUR or USP monographs, and they have been validated following guidelines in relevant Pharmacopeial General Chapters. There is a reference for each method, to the relevant monograph method, and the relevant pharmacopeial volume, and relevant pharmacopeial authority. In the absence of a compendial assay, a suitable method was developed and is described in detail including the required consumables.

In the absence of a compendial assay, a suitable method was developed and is described in detail including the required consumables.

• Lopinavir Assay
  
• Lopinavir and Ritonavir Tablets
• Chloroquine/Hydroxychloroquine
  
• Dexamethasone
• Remdesivir
• Fingolimod

Plasma-Derived Therapies

Plasma manufacturers are investigating plasma therapies as a treatment for COVID-19. Plasma production processes are highly variable depending on the production platform utilized. Please visit our Plasma Resource Center for information on common challenges in manufacturing plasma-derived therapies and how we can help you overcome them.

Please see our brochure for an overview of the products and services we have to support plasma-derived therapy manufacturing.

Relevant chromatography and TFF products for plasma can be found below.

Monoclonal Antibodies

mAb CDMO Services: BioReliance^® End-to-End Solutions

Your biotech company has discovered a promising molecule with the potential to develop a biologics drug against COVID-19? If you don’t have the in-house resources and capacity, we can develop and manufacture your treatment for you; offering a flexible model for engagement that can include fast-track development and no upfront payment or booking fees. Our adaptive CDMO solutions allow you to more effectively manage project risks and manage uncertainty, guiding you from cell line development and process development to GMP manufacturing.

Explore our end-to-end MaB manufacturing portfolio.

Products for mAb Manufacturing

From upstream to downstream, single-use or stainless steel, traditional or intensified processing, we have the full portfolio of chemicals, systems, and consumables to help you produce your monoclonal antibody.  

Explore our portfolio for every step of your mAb manufacturing.

Quality Control and Environmental Monitoring

Effective quality assurance, constant quality control and accurate results are key to manufacturing safe therapies. Our complete solutions for microbial detection and sterility assurance help you meet the highest quality standards and regulatory demands.

Many organizations are experiencing increased production demands as a result of the COVID-19 pandemic situation. The Milliflex Quantum^® system is a rapid microbial detection technology that can help reduce routine testing times significantly, providing results in 1/3 the time of traditional microbiology methods. This valuable time savings can be leveraged to facilitate early release of urgently needed supplies to their intended destination (medial, hospitals, labs).

Biosafety Testing Services

We’re here to partner with you. Our testing facilities are operating and we’re actively engaging the biopharma community to prioritize biosafety testing during this health crisis. Just as we did during Zika, SARS, and Ebola outbreaks, we’re here to support vaccine and therapeutic developers and manufacturers to prioritize therapies.

Learn more about our BioReliance^® Cell Line Characterization Services.

Learn more about our BioReliance^® Product Characterization Services.

Learn more about our BioReliance^® Viral Clearance Studies.

Learn more about our BioReliance^® Bulk Harvest Lot Release Testing and BioReliance^® Comprehensive Lot Release Testing.

BioReliance^® Vaccine Bulk Harvest Testing

Biosafety testing of vaccine bulk harvest and control cells involves a range of tests to demonstrate freedom from adventitious agents (bulk harvest and control cells) and to confirm identity of the vaccine material (bulk harvest). The choice of tests should be based on a viral safety risk assessment as well as relevant regulations and guidance documents and will typically address the following key areas:

• Detection and identification of vaccine gene of interest
• Vaccine virus titre
• Sterility, Mycoplasma and Mycobacterium
• Neutralization of vaccine virus for cell and in vivo based adventitious virus tests
• Adventitious viruses

Tests can be performed using a range of methods, from traditional cultivation and sequencing assays to state-of-the art rapid methods employing novel molecular methods such as Next Generation Sequencing and degenerate PCR. Contact info@bioreliance.com to discuss your needs.

Novel Modalities

Nucleic Acid Vaccines - Product and process related impurities

A variety of analytical methods are available to assess product purity. Typically, these will include a combination of orthogonal separation techniques, such as chromatography (RP-HPLC, SEC, IEX) and electrophoresis (CE-SDS). Additional assays can be employed to test for impurities specific to the particular product or process. For example, residual enzymes and DNA in RNA based products. Contact info@bioreliance.com to discuss your needs.

Virus & Viral-Like Therapies

Learn more about BioReliance^® Virus Bank Characterization.

Learn more about our BioReliance^® Cell Line Characterization Services.

Learn more about our BioReliance^® Product Characterization Services.

Learn more about our BioReliance^® Viral Clearance Studies.

Learn more about our BioReliance^® Bulk Harvest Lot Release Testing and BioReliance^® Comprehensive Lot Release Testing.

Learn more about our BioReliance^® Cell Banking and Biorepository Services.

BioReliance^® Vaccine Bulk Harvest Testing

Biosafety testing of vaccine bulk harvest and control cells involves a range of tests to demonstrate freedom from adventitious agents (bulk harvest and control cells) and to confirm identity of the vaccine material (bulk harvest). The choice of tests should be based on a viral safety risk assessment as well as relevant regulations and guidance documents and will typically address the following key areas:

• Detection and identification of vaccine gene of interest
• Vaccine virus titre
• Sterility, Mycoplasma and Mycobacterium
• Neutralization of vaccine virus for cell and in vivo based adventitious virus tests
• Adventitious viruses

Tests can be performed using a range of methods, from traditional cultivation and sequencing assays to state-of-the art rapid methods employing novel molecular methods such as Next Generation Sequencing and degenerate PCR. Contact info@bioreliance.com to discuss your needs.

• ATP Testing & Sanitation
  
• Labware
• Air Monitoring for Chemical Disinfectant Exposures
  

ATP Testing & Sanitation

Recent studies of the NIH showed that viable viruses can be detected after 2-3 days. The MVP Icon^® is a quick and easy-to-use system to check effectiveness of cleaning and disinfection procedures, even if viruses like SARS-CoV-2 are not directly measured. The MVP ICON^® measures the amount of adenosine triphosphate (ATP) in surface samples, an indicator of environmental contamination. Results are obtained in less than a minute and securely documented for subsequent evaluation. The MVP Icon^® helps you and your staff in a fast and easy way to monitor the success of cleaning and disinfection procedures.

Labware

Our Labware partner brands are chosen to bring our customers the best products from around the industry with easy access and seamless ordering for all of your PCR and RT-PCR needs.

Air Monitoring for Chemical Disinfectant Exposures

Applying cleaning agents such as chemical disinfectants and solvents to various work surfaces may release harmful chemical vapors and fumes and expose the employee to an inhalation risk from these hazardous chemicals. While workers wear personal protective equipment (PPE) to protect themselves from an exposure to the virus, it may not be suitable and effective in preventing an inhalation exposure from these chemical cleaning agents. 

Virus/Host Protein Analysis

Vital tools for analyzing virus and host proteins include the Duolink™ assay, Covidyte™ coronavirus protease substrates, industry-leading reagents for protein separation, and tools for mass spectrometry.

• Substrates for Coronavirus protease research
• Protein-protein interaction analysis/PLA
  
• Viral protein extraction and separation tools
  
• HPLC/UHPLC and Mass Spectrometry
  

Substrates and inhibitors for Coronavirus protease research

The coronavirus main protease (M^pro), plays a central role in viral gene expression and replication as the agent of proteolytic processing of replicase polyproteins, making it an opportune target for anti-CoV drug development. The inhibition of similar proteases has been an efficacious strategy in the treatment of HIV and hepatitis C, confirming the potential of protease inhibitors for the treatment of viral infections. Covidyte™ peptide substrates are compatible with high-throughput handling systems.

Protein-protein interaction analysis/PLA

Protein-protein interaction studies have recently been identified as important for SARS-CoV-2 research. The Duolink™ PLA (Proximity Ligation Assay) can be used to confirm endogenous protein-protein interaction in cells and tissues with a microscopy or flow cytometry readout.

 Viral and host protein extraction and separation tools

Affinity gels and columns, plus ready-to-use buffer for cell lysis provide rapid extraction of viral proteins on accelerated timelines, with accurate results. Learn how western blot can be used to confirm virus purification.

HPLC/UHPLC and mass spectrometry

Current research related to viruses relies increasingly on protein analysis by (U)HPLC  and mass spectrometry (MS), including MALDI (Matrix Assisted Laser Desorption Ionization). Our complete solutions for UHPLC, HPLC and MS analysis include columns and solvents optimized for these techniques.

RT-PCR Analysis

In addition to being used to aid in the diagnosis of COVID-19, reverse transcriptase–polymerase chain reaction (RT-PCR) is an indispensable technique in the SARS-CoV-2 research lab.

Reagents and tools for viral genetics analysis collected here include nucleic acid purification (NAP) kits for RNA purification, high-efficiency systems for RT-PCR and quantitative RT-PCR, cDNA synthesis kits, and more. Viral RNA extraction buffer lyses viral particles and stabilizes RNA from saliva ready for direct analysis via RT-qPCR with no additional cleanup step.

• RT-PCR Tools, Systems, and Kits
  
• Nucleic Acid Purification
  
• Molecular Decontamination and Water Solutions
• Plates, Tips and Labware for RT-PCR

RT-PCR Tools, Systems and Kits

One-step systems and  PCR master mixes can simplify and accelerate gene amplification across a wide dynamic range. TRI reagent accelerates isolation of nucleic acids and proteins from tissue.

Nucleic Acid Purification

GenElute™ Total RNA Purification Kits provide a rapid method for the isolation and purification of RNA from a variety of sample types, including viral RNA from cells, tissues, blood, and swabs. These kits are available in miniprep spin columns for efficient, rapid processing.

Molecular Decontamination and Water Solutions

Protect valuable nucleic acids from loss and degradation with nuclease-free water.

Plates, Tips and Labware for RT-PCR

Our labware tools are chosen to bring our customers the best selection of fit-for-purpose products from across the industry with easy access and seamless ordering for applications critical to viral studies including PCR and RT-PCR.

Sequencing

There is a growing need to sequence the viral genome of SARS-CoV-2 samples to better understand novel variants and their transmission. The PrimalSeq workflow using the ARTIC protocol has emerged as a key method for the study of SARS-CoV-2 by amplifying the viral genome sequence from cDNA. Reagents and tools collected here support NGS solutions for investigating the genome of COVID-19-positive samples.

Viral RNA Extraction

cDNA Synthesis

Multiplex PCR

Library Preparation

Sequencing

Common Reagents

*Not available in the US or Japan.

Virus Attachment & Entry

When a viral outbreak occurs, determining the mechanism of host cell attachment and entry is a priority. SARS-CoV-2 requires the host ACE-2 receptor for entry and exploits the serine protease TMPRSS2 for spike protein priming.

Collected here are cell lines for viral propagation and such unique in vitro models of the human respiratory epithelium as the 16HBE14o- line. Antibodies and small molecules specific for SARS-CoV-2 include ZooMAb® recombinant monoclonal and chimeric antibodies.

• Cell Lines for Virus Propagation and Respiratory Models
• Antibodies and Small Molecules for SARS-CoV-2 and Coronavirus Research
• ZooMAb^® Recombinant Monoclonal SARS-CoV-1/2  Antibodies
• ACE-2 Enzymatic Activity and Inhibitor Screening Kits

Cell Lines for Virus Propagation and Respiratory Models

Cell lines used to study SARS CoV viral attachment and propagation include Vero variants, Huh-7D, Caco-2, and 16HBE14o-, and are available below.

Antibodies and Small Molecules for SARS-CoV-2 and Coronavirus Research

Early research into the cellular entry mechanism has shown that SARS-CoV-2 uses the angiotensin converter enzyme II (ACE2) receptor for attachment and entry, and the serine protease TMPRSS2 for S protein priming. Find monoclonal and polyclonal antibodies and small molecules specific for relevant viruses and the receptors known to be exploited by them for cellular attachment and entry, including ACE2, and explore our groundbreaking ZooMAb^® recombinant antibodies against SARS-CoV-2-related targets.

Read our technical article for more information about SARS-CoV-2 proteins and relevant reagents.

ZooMAb^® Recombinant Monoclonal SARS-CoV-1/2 Antibodies

In response to the community’s need for highly specific and reproducible antibodies for SARS-CoV-1/2 research, our scientists have designed ZooMAb^® recombinant monoclonal antibodies against various SARS-CoV-1/2 targets. ZooMAb^® antibodies are all recombinantly produced, lyophilized, free of animal components, and offer our highest reproducibility to ensure optimal performance now and whenever you need them.

We are committed to providing researchers with the reagents and technical support during the COVID-19 outbreak. Explore our offering of ZooMAb^® recombinant monoclonal antibodies that are suitable for COVID-19 research.

ACE-2 Enzymatic Activity and Inhibitor Screening Kits

Angiotensin II-converting enzyme (ACE2) is a zinc-based metalloprotease and part of the renin-angiotensin system (RAS) that controls the regulation of blood pressure by cleaving the C-terminal dipeptide of Angiotensin II to convert it to Angiotensin 1-7. As a receptor of human coronaviruses such as SARS-CoV-2, ACE2 is a potential therapeutic target for cardiovascular and coronavirus-induced diseases, including COVID-19.

Screening for small molecule and peptide inhibitors may identify treatments for coronavirus-mediated infection. Read more.

Gene Editing

Find reagents here for shRNA or CRISPR approaches for knockdown or knockout of the ACE2 receptor and other genes relevant to SARS-CoV-2, available in plasmid, lentiviral and synthetic formats.

For additional information on viral gene editing, please visit our advanced genomics page.

shRNA ACE2

CRISPR ordering

Explore our Functional Genomics CRISPR and RNAi Libraries to find screening tools to determine which genes make cells more susceptible or resistant to COVID-19 infection, replication, and progression. These tools facilitate research into the development of genetic tests that can be used as secondary diagnostics when assessing predisposition for COVID-19 complications, as well as the risk of infection.