Immunoassays are used for routine potency assessment of several vaccines, in some cases having been specifically developed as alternatives to in vivo potency tests. These methods require at least one well characterised monoclonal antibody (mAb) that is specific for the target antigen. In this paper we report the results of the comprehensive characterisation of a panel of mAbs against diphtheria with

A new, simple and rapid method for the quantitative determination of the antimicrobial preservative 2-phenoxyethanol, based on reverse phase ultra-high-performance liquid chromatography has been developed. The validation was performed according the ICH Q2 guideline “Validation of Analytical Procedures”. The desired chromatographic separation was achieved on a Waters Symmetry C18 (150 × 4.6 mm, 5 μm)

The quality of antivenom is governed by its safety and efficacy profiles. These quality characteristics are much influenced by the purity of antivenom content. Rigorous assessment and meticulous monitoring of antivenom purity at the preclinical setting is hence crucial. This study aimed to explore an integrative proteomic method to assess the physicochemical purity of four commercially available antivenoms

To ensure the quality of raw materials for pharmaceutical products, the right storage and distribution temperature conditions should be applied. Labeled temperature conditions of 539 raw materials at non-cold chain conditions (thus excluding 2–8 °C or < 0 °C conditions) were reviewed that revealed a set of 26 different temperature requirements. From a manufacturer perspective, it is hard or undoable

Distressing effects on animal and human health with lethal progression, being used as bioweapon and shared features with non-pathogenic bacteria demands sensitive, specific, safe, cost effective and rapid detection methods for anthrax causing organisms. Conventional microbiology based diagnostics for anthrax are time consuming and need sophisticated equipment, while molecular diagnostics require less

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory condition with a wide spectrum of disease manifestations and severities, resulting in significant morbidity and mortality. The aetiopathogenesis of SLE is complex. Young women and certain ethnicities are commonly affected, suggesting a significant hormonal and genetic influence. Diverse immunological abnormalities have been described

FGF21 (Fibroblast Growth Factor 21), which is expressed in the liver, adipose tissue, and pancreas, has been widely known as a therapeutic candidate for metabolic diseases. Though FGF21 is crucial to glucose, lipid, and energy homeostasis, it is not straightforward to develop a new drug with FGF21 due to its short half-life in serum. Here, we derived a novel long-acting FGF21 (LAPS-FGF21), which is

Viral contamination is a major concern for biological products. Therefore, virus testing of raw materials and cells is essential for the safety of the final product. We used high-throughput sequencing to detect viral-like sequences in selected CHO cell lines. Our aim was to test various approaches of sample preparation, to establish a pipeline for metagenomic analysis and to characterize standard viral

Tremendous progress has been made in recent years to produce functional cells for cell therapy products. Hundreds of clinical trials of stem cell products (SCPs) have shown promising therapeutic potential worldwide, including the products derived from human pluripotent stem cells (hPSCs), adult stem cells and mesenchymal stem cells (MSC). Before starting a clinical trial, comprehensive chemistry, manufacturing

Human adipose tissue derived mesenchymal stem cells (hAD-MSCS) with suppressive immunogenicity, homing to injury, inflammatory, and cancer sites can be suitable for gene therapy. PiggyBac (PB) is a type of transposon vector applied in mammalian systems and could overcome some limitations of other transposon and viral vectors. In this study, the therapeutic potential hAD-MSCs expressing thrombospondin-1

Replacement of the potency tests for diphtheria vaccines is a high priority for the international initiative to reduce, refine, and replace animal use in vaccine testing. Diphtheria toxoid containing vaccine products marketed in the US currently require potency testing by the United States Public Health Service (USPHS) test, which includes an in vivo passive protection test with a diphtheria toxin

Helicobacter pylori CagA protein plays an important role in the severity of the gastric diseases. Our aims were to clone the cagA 5′- conserved region of the gene, characterize the recombinant CagA (rCagA) protein by monoclonal antibodies (mAbs) and to use this protein for the detection of anti-CagA antibodies by an ELISA test. Our developed rCagA protein (67 kDa) showed an amino acid sequence homology

In Japan, the practical application of completely cell-based seasonal influenza vaccines is under consideration. Considering the good correlation between the immunogenicity of egg-based influenza vaccines and the hemagglutinin (HA) content determined by the single radial immunodiffusion (SRD) assay, we determined the potency of the first cell-based quadrivalent vaccine experimentally generated in Japan

Markers associated to NK cytolytic activity are in a great need to regulate NK cell immunotherapy products. We assume that biomarkers which response to cytolysis will change their transcription, expression or secretion. To find NK-92 indicator to cytolytic activity, we have evaluated the potential markers by quantifying the expression of well-known cytotoxicity functional molecules (cytokine IFN-γ

Transition to in vitro alternative methods from in vivo in vaccine release testing and characterization, the implementation of the consistency approach, and a drive towards international harmonization of regulatory requirements are most pressing needs in the field of vaccines. It is critical for global vaccine community to work together to secure effective progress towards animal welfare and to ensure

This International Alliance for Biological Standardization COVID-19 webinar was organized to provide an update on the virology, epidemiology and immunology of, and the vaccine development for SARS-CoV-2, none months after COVID-19 was declared a public health emergency of international concern. It brought together a broad range of international stakeholders, including academia, regulators, funders

Mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are considered to be promising candidates for cell-based therapy of numerous skin disorders and wound healing. It is believed that MSCs differentiation into epithelial cells fill the area of the wound, while secretion of paracrine factors regulates cell homeostasis and adaptation. MSCs have been found to accelerate wound healing

Antibodies have strong affinity to their target molecules, a characteristic that is utilized in antibody drugs. For antibody drugs, target molecule specificity and long duration pharmacokinetics, along with strong affinity to the target molecule are important characteristics. Plasminogen activator inhibitor-1 (PAI-1) is one of the key regulators of the fibrinolysis system, and the benefits of PAI-1

Leningrad-Zagreb strain of mumps vaccine virus was grown on two different cell substrates viz. MRC-5 cells and Vero cells besides its original cell substrate i.e. Chicken Embryo Cells. Homogeneous virus pools prepared from each set of experiments were then lyophilized as per standard in-house protocol. Critical Quality Attributes (CQAs) such as the titer of the bulk vaccine and potency and stability

Hemin is one of the critical components of medium required for growth of Haemophilus influenzae type b (Hib) organisms. It is important to have different sources of critical components to ensure continuous supply for commercial production. Regulatory bodies also recommend having multiple sources for critical components. Hemin is produced from animal blood and the main sources are porcine and bovine

Current bacterial endotoxin testing systems can be labor-intensive and time-consuming, involving several manual pipetting steps. In our quality control laboratory, annually, we test about 15,000 samples of different grades of purified water, WFI and water samples taken to validate cleaning procedures for endotoxins. We are currently using the Kinetic-QCL™ assay which is a pharmacopeia method that provides

Heparin is an anticoagulant sourced from animal tissues. In the 1990s, bovine-sourced heparin was withdrawn from the U.S. market due to a theoretical concern that the bovine spongiform encephalopathy (BSE) agent might contaminate crude heparin and spread to humans as variant Creutzfeldt-Jakob disease. Only porcine intestinal heparin is now marketed in the U.S. FDA has encouraged the reintroduction

During vaccine production, RNA from chimeric yellow fever-dengue (CYD) vaccine viruses (CYD1, CYD2, CYD3 and CYD4) is currently quantified using separate serotype-specific RT-qPCR assays. Here we describe the results from a proof-of-concept study on the development of a multiplex reverse transcriptase droplet digital PCR (RT-ddPCR) assay for simultaneous quantification of RNA for all four viruses.

This second International Alliance for Biological Standardization COVID-19 webinar brought together a broad range of international stakeholders, including academia, regulators, funders and industry, with a considerable participation from low- and middle-income countries, to discuss the use of controlled human infection models to accelerate development and market authorization assessment of a vaccines

Effective decontamination procedures are critical to the successful manufacture and control of poliovirus vaccines to minimize the risk to personnel and the environment. Polio viruses have been reported to be more resistant to disinfectants than many other viruses. We assessed the efficacy of sodium hypochlorite-containing disinfectants for decontamination for three poliovirus serotypes to implement

The muscle-relaxing effects of the botulinum neurotoxin (BoNT) serotypes A and B are widely used in clinical and aesthetic medicine. The standard method for measuring the biological activity of pharmaceutical BoNT products is a mouse bioassay. In line with the European Directive 2010/63/EU, a replacement by an animal-free method would be desirable. Whereas the existing approved in vitro methods for

In recent years, several modified recombinant factor (F) VIII and FIX therapeutics with extended half-life have been licensed internationally for the treatment of haemophilia. Safe and effective use of these products requires monitoring of factor activity in patient plasma. The potency of all FVIII and FIX products is currently assigned in International Units (IU) which anchors the relationship between

New world Coral snakes comprise 82 species of medical importance distributed from southeastern United States to Argentina. In Colombia, Micrurus mipartitus and M. dumerilii are responsible for most coral snakebite accidents. Although infrequent, the severity of these envenomings, as well as the limited information available on the neutralizing coverage of commercially available antivenoms, underscores

Influenza is an acute respiratory infection caused by the influenza virus, and vaccination against influenza is considered the best way to prevent the onset and spread. MDCK (Madin-Darby canine kidney) cells are typically used to isolate the influenza virus, however, their high tumorigenicity is the main controversy in the production of influenza vaccines. Here, MDCK-C09 and MDCK-C35 monoclonal cell

Most antivenoms are produced by techniques developed over 50 years ago, with minor modifications. Herein we revise the core of traditional antivenom production processes aiming to optimize key determinants for both consistent antivenom production and the best balance between F(ab')2 quality and recovery. Factorial design analysis revealed that pepsin digestion of 1:3 saline diluted equine plasma for

During the training workshop on Inspection of Blood Establishments, which was hosted by the PEI GHPP BloodTrain in Harare from the 20th to the 24th of May 2019, participants from the National Regulatory Authorities from seven Sub-Sahara African countries presented their current experiences related to regulation and inspection of blood establishments in their respective countries. While in all seven

Classical swine fever (CSF) is an important viral disease of pigs and controlled by vaccination. Unorganised backyard and wild pigs are difficult to vaccinate by needle vaccination. Here we formulated liquid vaccines using an Indian CSF cell culture vaccine virus and four stabilisers and evaluated their stability at 4 °C, 25 °C and 37 °C up to 24 h for use as oral vaccine. The stabilisers were Lactalbumin

ABP 798 is a biosimilar candidate to rituximab reference product (RP). This comprehensive analytical similarity assessment was designed to assess the structural and functional similarity of ABP 798, rituximab (US), and rituximab (EU) using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. The similarity assessment was performed to evaluate

With the pandemic emergence of SARS-CoV-2, the exposure of cell substrates used for manufacturing of medicines has become a possibility. Cell lines used in biomanufacturing were thus evaluated for their SARS-CoV-2 susceptibility, and the detection of SARS-CoV-2 in culture supernatants by routine adventitious virus testing of fermenter harvest tested.

Several studies have investigated the use of simple in vitro tests for the assessment of rabies antibody titers in serum samples from vaccinated human subjects, which would allow the effectiveness of rabies vaccination to be conveniently evaluated. To this end, a novel time-resolved fluoroimmunoassay (TRFIA) for the assessment of rabies antibody titers was established in this study for evaluating the

The direct rapid immunohistochemical test (dRIT) has been recommended for laboratorial diagnosis of rabies, especially in developing countries. The absence of commercial primary antibodies, however, still represents a major limitation to its wider use in testing. We describe here the development of a biotinylated polyclonal antibody against Rabies lyssavirus (RABV) ribonucleoprotein (RNP) and its use

Adjuvants are a crucial component of recombinant vaccines such as the human papillomavirus (HPV) vaccine. Monophosphoryl lipid A (MPL) extracted from Salmonella Minnesota lipopolysaccharide is used as an adjuvant for the HPV vaccine. Due to the limitations in accessibility and reproducibility of MPL, investigating synthetic analogues of MPL (synMPL) is urgently needed to overcome these limitations

Plasmodium falciparum leads to a virulent form of malaria. Progress has been achieved in understanding the mechanisms involved in the malarial infection, still there is no effective vaccine to prevent severe infection. An effective vaccine against malaria should be one which can induce immune responses against multiple epitopes in the context of predominantly occurring HLA alleles. In this study, an

The IABS-EU, in association with PROVAXS and Ghent University, hosted the “2nd Conference on Next Generation Sequencing (NGS) for Adventitious Virus Detection in Human and Veterinary Biologics” held on November 13th and 14th 2019, in Ghent, Belgium. The meeting brought together international experts from regulatory agencies, the biotherapeutics and biologics industries, contract research organizations

Identification of Critical Quality Attributes (CQAs) and subsequent characterization in process development studies are the key elements of quality by design (QbD) for biopharmaceutical products. Since the inception of ICH Q8R2, several articles have been published on approaches to conducting CQA risk assessments as well as the application to process understanding. A survey was conducted by multiple

Bioburden control in the manufacturing facility is a serious concern regarding biologics due to the possibility of an significant economic impact due to batch failure from a bioburden incident. As a case study on effectively establishing a microbiological environmental monitoring program for cleanrooms, we focused on Time-lapse Shadow Image Analysis as a kind of Rapid Microbiological Method. In this

This first International Alliance for Biological Standardization Covid-19 webinar brought together a broad range of international stakeholders, including academia, regulators, funders and industry, with a considerable delegation from low- and middle-income countries, to discuss the virology, epidemiology and immunology of, and the vaccine development for SARS-CoV-2.

Typhoid vaccines based on protein-conjugated capsular Vi polysaccharide (TCVs) prevent typhoid in infants and young children. Analysis of the serum anti-Vi IgG response following immunisation against typhoid confirms the immunogenicity of TCVs and forms an important part of the pathway to licensing. Comparative studies could expedite the licencing process, and the availability of a standardised ELISA

Bone tissue-derive biomaterials have become of great interest to treat diseases of the skeletal system. Biological scaffolds of demineralized and decellularized extracellular matrices (ECM) have been developed and one of these options are ECM hydrogels derived from bovine bone. Nanomaterials may be able to regulate stem cell differentiation due to their unique physical-chemical properties. The present

The innocuity test was indicated as a quality control test to release pharmaceutical and biological products to the market. The test was intended to detect possible extraneous toxic contaminants derived from the manufacturing processes of the product. The test was included in WHO Recommendations and Guidelines for vaccines, biotherapeutics and blood products and in some monographs on antibiotics in

The third Human Challenge Trial Meeting brought together a broad range of international stakeholders, including academia, regulators, funders and industry, with a considerable delegation from Low- and Middle-Income Countries. Controlled human infection models (CHIMs) can be helpful to study pathogenesis and for the development of vaccines. As challenge agents are used to infect healthy volunteers,

The most critical parameter for the quality control of the rabies vaccine is potency, which is evaluated by challenge test in mice while using a large animal number. Because the 3Rs concept is applied worldwide, it becomes necessary to develop alternative methods to demonstrate the production consistency of these vaccines and reduce the number of animals used for performing assays. Hence, the present

Controlled human infection models can be helpful to study pathogenesis and immune responses as a basis for the development of vaccines. In controlled human infection models, human challenge agents are used to infect healthy volunteers, therefore, ethical considerations include that the exposure studies need to be safe and results should be meaningful, e.g. contribute to a better cure. Both in the US

Camelpox virus is the causative agent of Camelpox, a highly contagious disease of camels. A high passage Camelpox virus strain has previously been reported to contain several genes which more closely resemble Vaccinia, a virus species with no known natural host, encompassing various strains that show high inter-strain genomic variation. In this study, we demonstrate that yet another high passage, live

With the dramatic background of a newly emerged virus (SARS-CoV-2) spreading around the world, Coronavirus and other infectious health threats for the human and animal populations were illustrated and debated in excellent presentations at the IABS meeting 26–28 of February 2020. Historical evidence of pandemics and lessons learned from recent epidemics or epizootics caused by many pathogens (e.g.,

The World Health Assembly in 2014 adopted a resolution that mandates both Member States and the WHO Secretariat to facilitate access to biotherapeutic products in a way that ensures their quality, safety and efficacy. The availability of biosimilars is expected to increase access to biotherapeutic products by providing more treatment options triggering competition which would lead to a consistent reduction

Mycoplasma contamination threatens both the safety of biologics produced in cell substrates as well as the quality of scientific results based on cell-culture observations. Methods currently used to detect contamination of cells include culture, enzymatic activity, immunofluorescence and PCR but suffer from some limitations. High throughput sequencing (HTS) can be used to identify microbes like mycoplasmas

On the 17th of October 2019, a workshop was held at Wageningen Bioveterinary Research in Lelystad, the Netherlands, to discuss the obstacles to vaccination in the veterinary field. Participants from academia, OIE, FAO, EC, EMA, USDA, national regulatory and veterinary health authorities, and the animal health industry discussed how availability and access to animal vaccines can be improved not just

Immunoglobulin preparations are one of the promising drugs for Alzheimer's disease (AD). Anti-β-amyloid (Aβ) oligomers antibodies in immunoglobulin preparations are considered to be critical for the therapeutic effect against Alzheimer's disease. However, the antibodies content in immunoglobulin preparations varies greatly. In order to determine which factor contributes to the difference of the antibodies

The assay of Anti T lymphocyte immunoglobulin for final drug product testing is carried out using flow cytometry on Peripheral Blood Mononuclear Cells (PBMCs) as specified in European and British Pharmacopeia. An alternate assay was developed wherein the potency based quality control evaluation of Anti T lymphocyte immunoglobulin is carried out by measuring complement dependent cytotoxicity (CDC) using

Adventitious virus testing assures product safety by demonstrating the absence of viruses that could be unintentionally introduced during the manufacturing process. The capabilities of next-generation sequencing (NGS) for broad virus detection in biologics have been demonstrated by the detection of known and novel viruses that were previously missed using the recommended routine assays for adventitious

Rabies is a major neglected zoonotic disease and causes a substantial burden in the Asian region. Currently, Pacific Oceania is free of rabies but enzootic areas throughout southeast Asia represent a major risk of disease introduction to this region. On September 25–26, 2019, researchers, government officials and related stakeholders met at an IABS conference in Bangkok, Thailand to engage on the topic

Immune globulin subcutaneous, human 20% solution (IGSC-C 20%, Xembify®)—a new 20% immunoglobulin (IgG) liquid product for subcutaneous (SC) administration—has been developed by Grifols. The IGSC-C 20% formulation is based on knowledge acquired from the formulation of Immune Globulin Injection (Human),10% Caprylate/Chromatography Purified (IGIV-C 10%, Gamunex®-C). The protein concentration was increased