A modified caprylic acid method for manufacturing immunoglobulin G from human plasma with high yield and efficient virus clearance

Parkkinen, Jaakko; Rahola, A; Bonsdorff, Leni von; Tölö, Hannele; Törmä, E

doi:10.1111/j.1423-0410.2005.00731.x

Cited by 49 publications

(50 citation statements)

References 42 publications

(39 reference statements)

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“…PEI and caprylic acid have been implemented in microbial [37] and plasma processes [12,13,28], respectively. Acid precipitation and PDADMAC are being Industrial application of flocculation Review implemented in mAb production at large scale.…”

Section: Discussionmentioning

confidence: 99%

“…It has been used effectively to precipitate nonimmunoglobulin protein impurities from serum, plasma and ascites fluid [13,25,26]. It was also reported as an effective agent for inactivating enveloped viruses [27][28][29].…”

Section: Caprylic Acid Treatmentmentioning

confidence: 98%

“…In recent years, flocculation-based pretreatment of cell cultures for mAb production has been investigated [2,3,9,[12][13][14][15][16][17]. Many flocculation agents, or flocculants, ranging from simple electrolytes to synthetic polyelectrolytes (or polymers) have been evaluated (Table 1).…”

Section: Advances In Cell Culture Processes Drive Development Of Flocmentioning

confidence: 99%

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Industrial application of impurity flocculation to streamline antibody purification processes

Felo¹,

Kang

Hamzik³

et al. 2015

Pharmaceutical Bioprocessing

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Flocculation technologies offer significant benefits to industrial mammalian cell culture processes, including increased clarification efficiency, impurity removal and process simplification. In this paper, the application and performance of flocculation technologies employed in the harvest process of monoclonal antibody Chinese hamster ovary cell culture are reviewed. Attention has been placed on technologies enhancing the removal of cells, cellular debris and reduction in impurities while maintaining the antibody in the product stream. Many flocculants are systematically evaluated with respect to their mechanism of action, impact on downstream processing and product quality, and potential disadvantages. Practical considerations and future directions for application of flocculation in antibody manufacturing are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Caprylic Acid Treatmentmentioning

confidence: 98%

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Industrial application of impurity flocculation to streamline antibody purification processes

Felo¹,

Kang

Hamzik³

et al. 2015

Pharmaceutical Bioprocessing

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show abstract

“…The technique relies on caprylic (octanoic) acid precipitation of non-Ig molecules [14,15]. Caprylic acid is already used to prepare licensed IgG or IgM preparations from precipitates II+III [16,17], II [18], or III [18]; 5%-pH 5.5 caprylic acid precipitation is also used to produce horse plasma-derived therapeutic antivenom immunoglobulins [19,20], and this process may become an alternative to chromatography for monoclonal antibodies production [21]. …”

Section: Discussionmentioning

confidence: 99%

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

El‐Ekiaby¹,

Vargas

Moussa

et al. 2015

PLoS Negl Trop Dis

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BackgroundImmunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need.Methodology/Principal FindingsIgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment.Conclusions/Significance90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients. It is also relevant for preparing hyperimmune IgG from convalescent plasma during infectious outbreaks such as the current Ebola virus episode.

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“…The p19 fragment remains attached to the merozoite surface through a GPI anchor (Gerold et al, 1996) and is comprised of two epidermal growth factor (EGF)-like domains (Morgan et al, 1999), which may have a role in the invading complex. Serological studies have provided significant evidence suggesting that immune responses directed against the C-terminus of MSP-1 (MSP-1p19 and MSP-1p42) are associated with immunity in preclinical models (Long et al, 1994;Egan et al, 1999;Darko et al, 2005;Parkkinen et al, 2006). Moreover, protective immunity as defined by lower mortality and morbidity of individuals residing in endemic areas was also associated with MSP-1p19 (Egan et al, 1999;John et al, 2004).…”

Section: Msp-1 and Its Role In Immunity And Infectionmentioning

confidence: 99%

The Impact of Immune Responses on the Asexual Erythrocytic Stages of Plasmodium and the Implication for Vaccine Development

Bergmann‐Leitner¹,

Duncan²,

Angov³

2012

Malaria Parasites

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A modified caprylic acid method for manufacturing immunoglobulin G from human plasma with high yield and efficient virus clearance

Abstract: The new process gives pure and stable IgG solution with an average yield of 4.8 g of IgG per kg of recovered plasma and has a very high capacity to remove even physico-chemically resistant viruses.

Cited by 49 publications

References 42 publications

Industrial application of impurity flocculation to streamline antibody purification processes

Industrial application of impurity flocculation to streamline antibody purification processes

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

The Impact of Immune Responses on the Asexual Erythrocytic Stages of Plasmodium and the Implication for Vaccine Development

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