IGIV: Contents, properties, and methods of industrial production—evolving closer to a more physiologic product

Martin, Turf D.

doi:10.1016/j.intimp.2005.11.005

Cited by 50 publications

(38 citation statements)

References 19 publications

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“…Due to this and the limited availability of plasma, effective manufacturing processes are of great interest. Most current manufacturing processes for IVIG products use a combination of ethanol fractionation and ion exchange chromatography, and yield products with acceptable purity and safety profiles [32,33,53]. However, differences exist due to variations in starting materials, fractionation conditions and virus safety procedures.…”

Section: Discussionmentioning

confidence: 99%

“…Intravenous administration of Igs was therefore preferred, requiring highly purified products. In reality, this could be achieved by chromatographic purification, and therefore state of the art processes for Ig purification employ 1 or more column chromatography steps in addition to several means of reducing the transmission of possible contaminating viruses or other pathogens [29,30,31,32,33,34]. The aim of this work was to develop a high-yield process leading to a pure, safe, liquid IgG preparation for intravenous use (IVIG).…”

Section: Introductionmentioning

confidence: 99%

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Development, Manufacturing and Characterization of a Highly Purified, Liquid Immunoglobulin G Preparation from Human Plasma

Laursen

Blou

Sullivan

et al. 2014

Transfus Med Hemother

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Background: The use of plasma-derived immunoglobulin G (IgG) is increasing, and the number of diseases, including immunodeficiencies, neurological diseases and autoimmune conditions, treated with intravenous IgG (IVIG) is expanding. Consequently, there is a great need for high-yield production processes for plasma-derived IgG. The aim of this work was to develop a high-yield process leading to a highly purified, liquid, ready-to-use IgG for intravenous use. Methods: Plasma from healthy, voluntary, non-remunerated donors was fractionated by ethanol precipitation. IgG was extracted from fraction II + III using a phosphate/acetate buffer, pH 4, and purified by chromatography. Results: Precipitation with 6% polyethylene glycol at pH 7 removed high molecular-weight contaminating proteins, aggregates and contaminating viruses. Ion exchange chromatography at pH 5.7 on serially connected anion and cation exchange columns allowed for elution of IgG from the cation exchange column in good yield and high purity. Further safety was achieved by solvent/detergent treatment and repeated ion exchange chromatography. The product consisted of essentially only IgG monomers and dimers, and had a high purity with very low levels of IgM and IgA. Conclusion: A process providing highly purified IVIG in good yield was developed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development, Manufacturing and Characterization of a Highly Purified, Liquid Immunoglobulin G Preparation from Human Plasma

Laursen

Blou

Sullivan

et al. 2014

Transfus Med Hemother

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“…This process results in product purity with trace amounts of highly active contaminants such as prekallikrein activator, prekallikrein, activated coagulation factors, and complement proteins. These contaminants have the potential to cause clinically significant adverse events through their capability to activate the complement and through their opsonizing properties [5,16]. Therefore, many IVIG products undergo further purification via anion exchange diethylaminoethanol (DEAE)-sepharose chromatography, leading to a separation of IgG from fibrinogen, prekallikrein, IgM, and IgA [16].…”

Section: Standardized Gammaglobulin Preparationmentioning

confidence: 99%

“…These contaminants have the potential to cause clinically significant adverse events through their capability to activate the complement and through their opsonizing properties [5,16]. Therefore, many IVIG products undergo further purification via anion exchange diethylaminoethanol (DEAE)-sepharose chromatography, leading to a separation of IgG from fibrinogen, prekallikrein, IgM, and IgA [16]. The following section provides detailed information on each IVIG product, with a summary provided in table 2.…”

Section: Standardized Gammaglobulin Preparationmentioning

confidence: 99%

Immunoglobulin Replacement Therapy: A Twenty-Year Review and Current Update

Saeedian

Randhawa

2014

Int Arch Allergy Immunol

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Objective: The expansion of immunoglobulin replacement to multiple disease entities marks a decade-long advancement in immune therapy. Parallel to its extension, the characteristics and composition of immunoglobulin products have diversified. The aim of this study was to summarize a 20-year comprehensive literature review of currently commercially available immunoglobulin products, particularly examining individual product properties in a comparative format. Data Sources/Study Selections: The literature review was performed using PubMed and Ovid, screening a time span of 2 decades. Both authors reviewed the obtained articles for acceptable quality, and the selection was narrowed down based on criteria for randomized clinical and therapeutic trials. Results: Product-specific characteristics in terms of purification strategy, stabilizers, composition, and viral inactivation were found among the immunoglobulin products investigated. Such differing characteristics manifest in their variable clinical safety and efficacy as assessed by the comparative product analysis. In subgroups of patients, subcutaneous immunoglobulin therapy may be an alternative to intravenous immunoglobulin (IVIG) therapy with an equal efficacy and a lower number of systemic adverse events. Conclusion: Only few comprehensive clinical synopses are available to clearly demonstrate the differences in IVIG products despite the widespread clinical use of the therapy. This review defines significant characteristics of individual immunoglobulin products, noting important differences in product development and application and allowing informed clinical decisions to match a product with patients' risk factors and comorbidity. This balanced approach to gammaglobulin replacement therapy is imperative to produce the highest clinical efficacy and lowest number of adverse events.

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“…IgG, IgA and IgM), highly reactive aggregates and contaminants (prekallikrein activator, prekallikrein, activated coagulation factors) often remain in the preparation, which can activate the immune system such as the complement system causing a significant allergic reaction (Nesterova et al, 2009;Radosevich & Burnouf, 2010). Hence, IVIg preparations undergo a second processing step such as anion exchange diethylaminoethanol (DEAE)-sepharose chromatography to separate IgG from contaminants to ensure the preparation primarily contains immunoglobulins (Laursen et al, 2014;Martin, 2006).…”

Section: Intravenous Immunoglobulin (Ivig): Preparation and Compositimentioning

confidence: 99%

The role of inflammasomes in ischemic stroke - from pathophysiology to treatments

Fann¹

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Stroke is the second leading cause of mortality worldwide and a major cause of long-term disability. Clinically, stroke can be classified as either ischemic or haemorrhagic. Ischemic stroke is the most common type of stroke and accounts for approximately 80% of all stroke cases. The pathophysiological processes following stroke are complex and extensive, and include bioenergetic failure, excitotoxicity, oxidative stress and inflammation, which leads to necrotic and apoptotic cell death. Recent findings have provided insight into a newly described inflammatory mechanism that may contribute to neuronal and glial cell death during cerebral ischemia known as sterile inflammation involving intracellular multi-protein complexes termed inflammasomes. Despite neuroprotective agents decreasing neuronal cell death and infarct size under in vitro and in vivo stroke models, respectively, all such agents tested in stroke patients have failed in clinical trials. Novel potential therapies envisaged to target multiple cell injury mechanisms in the brain following cerebral ischemia include-intravenous immunoglobulin (IVIg) and intermittent fasting (IF). IVIg is a purified polyclonal immunoglobulin preparation obtained from the plasma of several thousand healthy donors. Numerous experimental studies by our laboratory demonstrated that administration of IVIg was able to significantly attenuate brain injury in mice subjected to experimental stroke. Moreover, IF is a form of dietary energy restriction and encompasses alternate periods of ad libitum feeding and fasting, which have been proven to decrease the development of age-related diseases. Previous experimental studies demonstrated that IF was able to significantly attenuate brain injury outcome in mice subjected to experimental stroke. However, the precise mechanism(s) in how IVIg and IF directly protect neurons and cerebral tissue from inflammasome-mediated sterile inflammation following ischemic stroke remains to be determined and is a major focus of this research thesis. In the first study of this research thesis, we performed a comprehensive investigation into the expression patterns of NLRP1 and NLRP3 inflammasome proteins and both IL-1β and IL-18 in mouse primary cortical neurons subjected to simulated ischemia and in a model of focal ischemic stroke in C57BL/6J mice. In addition, determined whether the NLRP1 and NLRP3 inflammasome could be targeted with a Caspase-1 inhibitor and IVIg for therapeutic intervention. The study demonstrated that ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins and both IL-1β and IL-18 in neurons and brain tissues. Moreover, Caspase-1 II inhibitor and IVIg treatment protected neurons and brain tissue by a mechanism(s) involving Caspase-1 inhibition and suppression of NLRP1 and NLRP3 inflammasome activity, respectively, under in vitro and in vivo ischemic conditions. In the second study of this research thesis, we provide evidence that the NF-κB and MAPK(s) signaling pathways are involved in regulating the ...

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IGIV: Contents, properties, and methods of industrial production—evolving closer to a more physiologic product

Cited by 50 publications

References 19 publications

Development, Manufacturing and Characterization of a Highly Purified, Liquid Immunoglobulin G Preparation from Human Plasma

Development, Manufacturing and Characterization of a Highly Purified, Liquid Immunoglobulin G Preparation from Human Plasma

Immunoglobulin Replacement Therapy: A Twenty-Year Review and Current Update

The role of inflammasomes in ischemic stroke - from pathophysiology to treatments

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