Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration

Alonso, William R.; Vandeberg, Pete; Lang, John M.; Yuziuk, Jeffrey; Silverstein, Rebecca; Stokes, Kenya; McBride, D.; Cruz, Maricel Dela; Burns, Doug; Merritt, W. Keither; Willis, Todd; Jorquera, Juan I.

doi:10.1016/j.biologicals.2020.01.004

Cited by 10 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pooled convalescent plasma was subjected to alcohol fractionation and caprylate/chromatography purification, resulting in highly purified IgG solutions formulated at 10% protein with glycine at a low pH. These production processes, including formulation, are identical to those for Gamunex immune globulin 11,12 . These processes include multiple steps validated for the removal and/or inactivation of viruses 13 .…”

Section: Methodsmentioning

confidence: 99%

“…Analyses are also performed for sodium caprylate, residual IgA and IgM, prekallikrein activator, factor XIa, anti‐A, anti‐B, and anti‐D. These tests have recently been described for other immune globulin products manufactured with the caprylate/chromatography process 12 . In addition, compendial tests for sterility and pyrogenic substances are performed on all batches 14…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Production of anti‐SARS‐CoV‐2 hyperimmune globulin from convalescent plasma

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti‐SARS‐CoV‐2 hyperimmune globulin (hIVIG). Study Design and Methods Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small‐scale facility designed and built to rapidly address emerging infectious diseases. Results Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS‐CoV‐2 were increased over 10‐fold from convalescent plasma to the final product. Normalized enzyme‐linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti‐A, anti‐B, and anti‐D) were reduced to minimal levels. Conclusions Multiple batches of anti‐SARS‐CoV‐2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti‐Coronavirus Immunoglobulin (ITAC) [NCT04546581].

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Production of anti‐SARS‐CoV‐2 hyperimmune globulin from convalescent plasma

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, there are some unwanted factors present in human plasma, such as growth factors, IgA, and IgE, which may result in adverse outcomes and allergic reactions. Approximately 98% IVIg is IgG prepared from several thousands of healthy blood donors; human IVIg may be a good agent for anticancer therapy and other treatments such as primary humoral immunodeficiency, inflammation and autoimmune diseases (Corbí et al, 2016;Alonso et al, 2020). Both in vitro studies and animal models showed that IVIg could inhibit the growth and spreading of several types of solid cancer, such as melanoma, colon cancer, breast cancer and sarcoma (Fishman et al, 2002;Sapir et al, 2005;Schwartz-Albiez et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Circulating Natural Autoantibodies to HER2-Derived Peptides Performed Antitumor Effects on Oral Squamous Cell Carcinoma

Liu

He²,

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Natural autoantibodies play a crucial role in destruction of malignant tumors due to immune surveillance function. Epidermal growth factor receptor 2 (HER2) has been found to be highly expressed in a variety of epithelial tumors including oral squamous cell carcinoma (OSCC). The present study was thus undertaken to investigate the effect of anti-HER2 natural autoantibodies on OSCC. Compared with cancer-adjacent tissues, cancer tissues from OSCC patients exhibited higher HER2 expression especially in those with middle & advanced stage OSCC. Plasma anti-HER2 IgG levels examined with an enzyme-linked immunosorbent assay (ELISA) developed in-house showed differences between control subjects, individuals with oral benign tumor and patients with OSCC. In addition, anti-HER2 IgG-abundant plasma was screened from healthy donors to treat OSCC cells and to prepare for anti-HER2 intravenous immunoglobulin (IVIg). Both anti-HER2 IgG-abundant plasma and anti-HER2 IVIg could significantly inhibit proliferation and invasion of OSCC cells by inducing the apoptosis, and also regulate apoptosis-associated factors and epithelial-mesenchymal transition (EMT), respectively. Besides, the complement-dependent cytotoxicity (CDC) pathway was likely to contribute to the anti-HER2 IgG mediated inhibition of OSCC cells. After the HER2 gene was knocked down with HER2-specific siRNAs, the inhibitory effects on OSCC cell proliferation and apoptotic induction faded away. In conclusion, human plasma IgG, or IVIg against HER2 may be a promising agent for anti-OSCC therapy.

show abstract

“…These production processes, including formulation, are identical to those for Gamunex immune globulin. 11,12 These processes include multiple steps validated for the removal and/or inactivation of viruses. 13…”

Section: Methodsmentioning

confidence: 99%

“…These tests have recently been described for other immune globulin products manufactured with the caprylate/chromatography process. 12 In addition, compendial tests for sterility and pyrogenic substances are performed on all batches. 14,15 Anti-SARS-CoV-2 ELISA…”

Section: Routine Batch Testingmentioning

confidence: 99%

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma

Vandeberg

Cruz

Díez

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

BACKGROUNDIn late 2019, the SARS-CoV-2 virus emerged in China and quickly spread into a world-wide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG).STUDY DESIGN AND METHODSConvalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases.RESULTSProcessing convalescent plasma into hIVIG resulted in a highly purified IgG product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG antibody specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized ELISA activity (per mg/mL IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B and anti-D antibodies) were reduced to minimal levels.CONCLUSIONSMultiple batches of anti-SARS-CoV-2 hyperimmune globulin (hIVIG) that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].

show abstract

Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration

Cited by 10 publications

References 19 publications

Production of anti‐SARS‐CoV‐2 hyperimmune globulin from convalescent plasma

Production of anti‐SARS‐CoV‐2 hyperimmune globulin from convalescent plasma

Circulating Natural Autoantibodies to HER2-Derived Peptides Performed Antitumor Effects on Oral Squamous Cell Carcinoma

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma

Contact Info

Product

Resources

About