UK National Institute for Biological Standards and Control

Potters Bar, United Kingdom

UK National Institute for Biological Standards and Control

Potters Bar, United Kingdom

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Sesardic T.,UK National Institute for Biological Standards and Control
Current Opinion in Microbiology | Year: 2012

Bioassays play central role in evaluation of biological products and those derived from bacterial toxins often rely exclusively on in vivo models for assurance of safety and potency. This chapter reviews existing regulatory approved methods designed to provide information on potency and safety of complex biological medicines with an insight into strategies considered for alternative procedures. © 2012 Elsevier Ltd.


Thorpe S.J.,UK National Institute for Biological Standards and Control
Transfusion | Year: 2015

Intravenous immunoglobulin (IVIG) products are generally safe and efficacious, although treatment-related adverse reactions can occur in recipients. Adverse reactions include hemolysis in non-blood group O recipients linked to the passive transfer of anti-A and/or anti-B present in the fractionated immunoglobulin product. In light of the recent increase in reported cases of severe hemolysis associated with anti-A and/or anti-B, this article traces the development of pharmacopoeial specifications, tests, and reference reagents to control their titers in IVIG products. © 2015 AABB.


Minor P.D.,UK National Institute for Biological Standards and Control
Virology | Year: 2015

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. © 2015 The Author.


Stacey G.,UK National Institute for Biological Standards and Control
Advances in Experimental Medicine and Biology | Year: 2012

The ideal features of a cell culture system for in vitro investigation depend on what questions the system is to address. However, in general, highly valuable systems will replicate the characteristics and more specifically, the responses, of normal human tissues. Systems that can faithfully replicate different tissue types provide tremendous potential value for in vitro research and have been the subject of much research effort in this area over many years. Furthermore, a range of such systems that could mimic key genetic variations or diseases would have special value for toxicology and drug discovery. In the pursuit of such model systems, there are a number of significant practical issues to consider for their application, which includes ability to deliver with ease, the required quantities of cells at the time needed. In addition any cell culture assay will need to be robust and reliable and provide readily interpreted and quantified endpoints. Other general criteria for cell culture systems include scalability to provide the very large cell numbers that may be required for high throughput systems, with a high degree of reliability and reproducibility. The amenability of the cell culture for down-scaling may also be important, to permit the use of very small test samples (e.g., in 96-well arrays), even down to the level of single cell analysis. This chapter explores the range of new cell culture systems for scaling up cell cultures that will be needed for high throughput toxicology and drug discovery assays. It also reviews the increasing range of novel systems that enable high content analysis from small cell numbers or even single cells. The hopes and challenges for the use of human stem cell lines are also investigated in comparison with the range of eukaryotic cells types currently in use in toxicology. © 2012 Landes Bioscience and Springer Science+Business Media.


Thelwell C.,UK National Institute for Biological Standards and Control
Seminars in Thrombosis and Hemostasis | Year: 2014

Thrombolytic drugs are used for the treatment of thrombotic disorders such as acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. Biological standards are used for potency assignment to the range of fibrinolytic proteins used in thrombolytic therapy. The World Health Organization (WHO) International Standards are primary reference materials, calibrated in arbitrary units (international unit), assigned by collaborative study using the range of assay methods available at the time. Provided the standard and test material are equivalent, adhering to the principle of measuring like versus like, the exact nature of the assay method is unimportant. This approach has been applied successfully for several decades since the advent of fibrinolytic treatment, ensuring consistency for potency labeling and the correct dosing of patients. The emergence of generic biosimilar products and new recombinant variants poses a challenge to this system, where functional differences impact on the relative biological activity in different assay systems. A more demanding system of standardization may therefore be required on the basis of international reference materials with associated reference methods. WHO recognizes this, and where possible and practical is seeking to incorporate concepts of traceability, uncertainty, and commutability to International Standards. However, some caution is needed because limitations on the characterization of many complex biologicals remain real, and a flexible approach is required on the basis of real-world needs. © 2014 by Thieme Medical Publishers, Inc.


Hubbard A.R.,UK National Institute for Biological Standards and Control
Seminars in Thrombosis and Hemostasis | Year: 2015

Various strategies to produce longer-lasting factor VIII and factor IX concentrates through chemical and genetic modifications are currently under evaluation. It is now clear that these new molecules are amenable to testing using conventional methods for biological activity (one-stage clotting and chromogenic) and there is a preference to maintain labeling in International Units (IU) traceable to the WHO International Standard Concentrates. This is an achievable goal; however, many of the new molecules are associated with potency discrepancies both between methods and also within methods, for instance, when different activated partial thromboplastin time reagents are used. In the interests of global harmonization, it is important for licensing authorities to reach agreement on the choice of the potency labeling method. This choice should be supported by a thorough characterization of product potency, both in vitro and in vivo, to anticipate future issues and with a view to maintaining equivalence of the IU compared with existing licensed products. In cases where the product potency is defined using specific reagents, the robustness of the manufacturer's product standard will be crucial for product consistency. The sensitivity of measured potency to different methodologies will require manufacturers to provide guidance to clinical laboratories on suitable postinfusion testing approaches.


Rider C.C.,Royal Holloway, University of London | Mulloy B.,UK National Institute for Biological Standards and Control
Biochemical Journal | Year: 2010

The BMPs (bone morphogenetic proteins) and the GDFs (growth and differentiation factors) together form a single family of cystine-knot cytokines, sharing the characteristic fold of the TGF-β (transforming growth factor-β) superfamily. Besides the ability to induce bone formation, which gave the BMPs their name, the BMP/GDFs display morphogenetic activities in the development of a wide range of tissues. BMP/GDF homo- and hetero-dimers interact with combinations of type I and type II receptor dimers to produce multiple possible signalling complexes, leading to the activation of one of two competing sets of SMAD transcription factors. BMP/GDFs have highly specific and localized functions. These are regulated in a number of ways, including the developmental restriction of BMP/GDF expression and through the secretion of several specific BMP antagonist proteins that bind with high affinity to the cytokines. Curiously, a number of these antagonists are also members of the TGF-β superfamily. Finally a number of both the BMP/GDFs and their antagonists interact with the heparan sulphate side chains of cellsurface and extracellular-matrix proteoglycans. © The Authors.


Patent
Baxter International, Baxter Healthcare S.A., UK National Institute for Biological Standards and Control | Date: 2010-04-26

An improved monocyte activation test is described that is better able to detect non-endotoxin pyrogens in medical products, in which a sample is incubated with a monocyte-containing reagent in an assay system comprising at least one surface comprising polypropylene. The invention also concerns assay systems for use in these tests that include at least one microtiter well having at least one interior surface comprising polypropylene and having a shape such that monocyte-containing reagent is concentrated in the well to provide greater cell to cell contact. The invention also relates to a diagnostic kit that can be used to test for the presence of non-endotoxin pyrogens in a sample.


Patent
Baxter International, Baxter Healthcare S.A., UK National Institute for Biological Standards and Control | Date: 2010-04-26

An improved monocyte activation test is described that is better able to detect non-endotoxin pyrogens in medical products, in which a sample is incubated with a monocyte-containing reagent in an assay system comprising at least one surface comprising polypropylene. The invention also concerns assay systems for use in these tests that include at least one microtiter well having at least one interior surface comprising polypropylene and having a shape such that monocyte-containing reagent is concentrated in the well to provide greater cell to cell contact. The invention also relates to a diagnostic kit that can be used to test for the presence of non-endotoxin pyrogens in a sample.


News Article | February 15, 2017
Site: www.nature.com

International rules to ensure that developing countries benefit when foreign companies make use of their biological resources could delay the supply of seasonal influenza vaccines or render those vaccines less effective, warn vaccine manufacturers and researchers. The Nagoya Protocol dictates that any company using ‘genetic resources’ from a participating nation must negotiate an agreement to ensure that any profits or benefits are shared. That could include making payments or sharing research results or intellectual property. The treaty covers samples from plants, animals and, crucially, the viruses used to create vaccines. The treaty came fully into force in October 2015. But there are concerns that the need to negotiate agreements may hamper companies’ ability to manufacture the best vaccines in time for the next flu season. The executive board of the World Health Organization (WHO) discussed the public-health impact of the treaty, including how it affects vaccines, at a meeting on 27 January. Pharmaceutical companies have raised concerns with the WHO and with governments. International experts meet twice a year — in time for both Northern and Southern Hemisphere winters — to determine which viral strains should be included in the vaccines for the coming flu seasons. The process is conducted by the WHO’s Global Influenza Surveillance and Response System (GISRS), which collects and analyses the latest viral samples from around the world. When the advice changes, “it’s a race against time” to incorporate the new strains into the vaccines, says John McCauley, director of the Crick Worldwide Influenza Centre in London, which is part of the GISRS. “It’s really, really time-pressured.” Of the four virus strains in the current flu vaccine (2016–17), three pre-date the convention and one is from the United States, which has not ratified the treaty. But at some point, the recommendations could change to include samples that fall under the treaty. Currently, 95 parties are bound by the Nagoya Protocol, including the European Union, China, India and Indonesia, and some countries, such as Brazil, have their own legislation that has a similar effect. The GISRS panel is due to meet in New York at the end of the month to determine recommendations for the Northern Hemisphere winter in 2017–18. At present, companies have approximately six months to implement any recommended changes before the flu season starts (see ‘Race to make flu vaccine’). But the need to reach benefit-sharing agreements could introduce delays “conservatively estimated to be a minimum of three months”, says London-based AstraZeneca, which manufactures flu vaccines. This could mean that vaccines would not reach patients until influenza is already circulating. Such a delay “would place public health at significant risk”, the company says. “We would be concerned if Nagoya Protocol-related obligations caused delays or other problems in seasonal flu vaccines being made available for vaccination,” adds a spokesperson from GlaxoSmithKline in Brentford, UK. Another possibility is that companies could simply avoid certain strains if the legality of their use is uncertain, says Stephen Inglis, who until last year headed the UK National Institute for Biological Standards and Control near London. This could mean that the resulting vaccine is a poor match for circulating strains. Although Inglis thinks that the Nagoya Protocol “is based on a very noble principle”, he questions whether it should include pathogens. But Edward Hammond, who worked on the creation of a WHO sharing system for zoonotic flu samples known as the Pandemic Influenza Preparedness (PIP) Framework on behalf of the Third World Network, says that it is right that pathogens be included in the treaty — and that companies share the benefits of products made from them. Hammond, an independent research consultant in Austin, Texas, says that it should take only a few years to come up with a system for seasonal flu that does not require individual agreements but does include benefits-sharing — in the meantime, there will be just a “handful” of strains that come from treaty-bound nations. One solution along these lines would be to turn the WHO–GISRS system into a formal international agreement that incorporates benefit sharing and is therefore recognized by the Nagoya Protocol: then, samples could be shared without making separate agreements. A similar option is being pursued for the PIP Framework in response to Nagoya. But McCauley notes that the system for seasonal influenza involves many more samples. “The necessary extra work under the PIP Framework,” he says, “would be very likely to reduce the number of viruses that are shared for seasonal influenza.”

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