Human Intravenous Immunoglobulin Preparation and Virus Inactivation by Pasteurization and Solvent Detergent Treatment

Chang, Chong E.; Eo, Ho Gueon; Lee, Yoon Sung; Chung, Soon Kwan; Shin, Jeong Sup; Lah, Yoon Kyung; Park, Chan Woo; Jung, Jin Taek; Huh, Jae Wook; Lee, Soung Min

doi:10.1080/10826060008544957

Cited by 11 publications

(4 citation statements)

References 30 publications

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“…Stabilizers include sugars, like sucrose, or polyols, such as sorbitol [65,66]. Pasteurization of IVIG can lead to the inactivation of both enveloped and at least, and usually to a lesser extent, some non‐enveloped viruses [65,67]. Stabilizers are removed after pasteurization by procedures like ultrafiltration.…”

Section: Viral Reduction Methodsmentioning

confidence: 99%

“…In most processes the incubation lasts at least 1 to 6 h and is carried out at 20–35°C. The process is very effective against lipid‐enveloped viruses but cannot inactivate non‐enveloped viruses [65,67]. The removal of the S/D agents can be integrated within the intended purification scheme through adsorption of the IgG on a chromatographic medium.…”

Section: Viral Reduction Methodsmentioning

confidence: 99%

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Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance

2010

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Intravenous immunoglobulin G (IVIG) is now the leading product obtained by fractionation of human plasma. It is the standard replacement therapy in primary and acquired humoral deficiency, and is also used for immunomodulatory therapy in various autoimmune disorders and transplantation. Over the last 30 years, the production processes of IVIG have evolved dramatically, gradually resulting in the development of intact IgG preparations safe to administer intravenously, with normal half-life and effector functions, prepared at increased yield, and exhibiting higher pathogen safety. This article reviews the developments that have led to modern IVIG preparations, the current methods used for plasma collection and fractionation, the safety measures implemented to minimize the risks of pathogen transmission and the major quality control tests that are available for product development and as part of mandatory batch release procedures.

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Section: Viral Reduction Methodsmentioning

confidence: 99%

Section: Viral Reduction Methodsmentioning

confidence: 99%

Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance

2010

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“…S/D treatment is very effective against lipid-enveloped viruses (Uemura et al, 1994;Chang et al, 2000). Low pH incubation also provides robust inactivation of lipidenveloped viruses, including HIV (Bos et al, 1998;Omar et al, 1996;Biesert, 1996;Reid et al, 1988).…”

Section: Resultsmentioning

confidence: 99%

Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

Gouveia

Oliveira

Lucena³

et al. 2013

Braz. J. Pharm. Sci.

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Dengue represents an important health problem in Brazil and therefore there is a great need to develop a vaccine or treatment. The neutralization of the dengue virus by a specific antibody can potentially be applied to therapy. The present paper describes, for the first time, the preparation of Immunoglobulin specific for the dengue virus (anti-DENV IgG), collected from screened Brazilian blood-donations. Production was performed using the classic Cohn-Oncley process with minor modifications. The anti-DENV IgG was biochemically and biophysically characterized and fulfilled the requirements defined by the European Pharmacopoeia. The finished product was able to neutralize different virus serotypes (DENV-1, DENV-2, and DENV-3), while a commercial IgG collected from American blood donations was found to have low anti-dengue antibody titers. Overall, this anti-DENV IgG represents an important step in the study of the therapeutic potential and safety of a specific antibody that neutralizes the dengue virus in humans.Uniterms:. Viral infections. Dengue/treatment. Dengue/virus/neutralization. Immunoglobulins/ preparation. Plasma fractionation. Virus neutralization.A dengue representa um importante problema de saúde no Brasil, portanto, a identificação de vacina ou tratamento eficaz é uma necessidade urgente. A neutralização do vírus da dengue, por anticorpo específico, tem potencial aplicação terapêutica. Descrevemos aqui, pela primeira vez, a preparação de imunoglobulina específica para o vírus da dengue (IgG anti-DENV), produzida a partir do plasma selecionado de doadores brasileiros. A produção foi realizada utilizando o método clássico de Cohn-Oncley com pequenas modificações. A IgG anti-DENV foi bioquimicamente e biofisicamente caracterizada e cumpriu os requisitos definidos pela Farmacopeia Europeia. O produto final foi capaz de neutralizar diferentes sorotipos do vírus (DENV-1, DENV-2 e DENV-3), enquanto que a IgG comercial, produzida a partir do plasma de doadores americanos, apresentou baixos títulos de anticorpos anti-dengue. No geral, esta IgG anti-DENV representa uma importante etapa para o estudo do potencial terapêutico e segurança da neutralização, por anticorpos específicos, do vírus da dengue em humanos.Unitermos: Infecções virais. Dengue/tratamento. Dengue/vírus/neutralização. Imunoglobulinas específicas/preparação. Fracionamento de plasma. Neutralização viral. INTRODUCTIONThere are around 2.5 billion people living in areas endemic for dengue fever and it is estimated that there are 100 million infections annually (Gubler 1998). The burden of dengue in endemic countries weighs heaviest on children. However, there has been an increasing trend towards adult infection in certain countries (Ooi, Goh, Gubler, 2006;Cummings et al., 2009). Most travelers with dengue have been adults (Wilder-Smith, Schwartz, 2005). Currently, neither cure nor vaccines are available, and new therapies are thus urgently needed. Although there have been considerable developments in medicinal chemistry, no promising small-organic...

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“…A methodology of IV IgG production, fully developed by liquid chromatography, has also been described (Tanaka, 1998). Although liquid chromatography processes have an established role in the protein purification industry, precipitation techniques for primary isolation of biological material continue to attract the interest of researchers, mainly because of their low cost (Chang, 2000;Buchacher, 2006).…”

Section: Introductionmentioning

confidence: 99%

A new methodology for polyvalent intravenous immunoglobulin solution production with a two-stage process of viral inactivation

Lucena

Sampaio

Silva

et al. 2010

Braz. J. Pharm. Sci.

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Highly purified intravenous immunoglobulin G concentrate (IV IgG) was produced with the use of polyethylene glycol associated to a single-stage precipitation by ethanol, instead of the classic Cohn-Oncley process, which employs cold alcohol as the precipitating agent, in a three-stage process. Precipitation of crude fraction containing more than 95% of immunoglobulin G was performed by liquid chromatography with a cation exchanger, CM-Sepharose, as a stationary phase. During the process, the product was subjected to two-stage viral inactivation. The first stage was performed by the action of sodium caprylate, 30 mM at pH 5.1+/- 0.1, and the second stage was performed by the action of a solvent-detergent mixture. The finished product was formulated at 5% with 10% sucralose as the stabilizing agent. The process yields 3.3g of IgG/liter of plasma. The finished product analysis showed an anti-complementary activity lower than 1CH50. Polymer and aggregate percent levels were lower than 3% in the five batches studied. The analysis of neutralizing capacity showed the presence of antibacterial and antiviral antibodies in at least three times higher concentrations than the levels found in source plasma. The finished product fulfilled all purity requirements stated in the 4th edition of the European pharmacopeia.
Obteve-se concentrado de imunoglobulina G intravenosa IgGIV, altamente purificado, utilizando-se polietilenoglicol associado a uma única etapa de precipitação por etanol, em substituição ao tradicional método descrito por Cohn-Oncley, que emprega, em três etapas, o mesmo álcool resfriado, como agente precipitante. A purificação da fração bruta contendo mais de 95% de imunoglobulina G foi realizada utilizando-se cromatografia líquida com um trocador de cátion, a CM-Sepharose, como fase estacionária. Durante o processamento o produto foi submetido a dupla inativação viral sendo a primeira pela ação do caprilato de sódio, 30 mM a pH 5,1+/- 0,1 e a segunda por ação de mistura de solvente/detergente. O produto acabado foi formulado a 5% utilizando-se sucralose 10% como estabilizante. O rendimento da metodologia foi de 3,3g de IgG/litro de plasma. A análise do produto acabado demonstrou atividade anti-complementar inferior a 1CH50. O valor percentual de polímeros e agregados em cinco lotes realizados foi inferior a 3%. O estudo da capacidade de neutralização demonstrou a presença de anticorpos anti-bacterianos e anti-virais em concentração pelo menos três vezes maior que o plasma de origem. O produto acabado apresentou conformidade com todos os requisitos de pureza dispostos na farmacopéia européia IV edição

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Human Intravenous Immunoglobulin Preparation and Virus Inactivation by Pasteurization and Solvent Detergent Treatment

Cited by 11 publications

References 30 publications

Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance

Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance

Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

A new methodology for polyvalent intravenous immunoglobulin solution production with a two-stage process of viral inactivation

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