Immunoglobulins M Survive Low-pH Conditions Used for Virus Inactivation and for Elution from Bioaffinity Columns

Mueller, Monika; Wan, Corrine; Hoi, Kong Meng; Kim, Do Yun; Gan, Hui Theng; Bardor, Muriel; Gagnon, Pete

doi:10.1002/jps.23428

Cited by 7 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This different influence of pH was described by some authors and can be explained by a change in the charge of the protein surface that results in the denaturation of IgG, probably leading to unfolding of the antigen‐binding region . Similar results were published in the case of IgM produced from hybridomas cultivated in in‐house serum‐free medium. The immunoglobulins maintained their activity at pH 3.5 after 1 h of treatment at room temperature.…”

Section: Resultssupporting

confidence: 80%

“…The influence of temperature and pH on the antigen‐binding capacity (ABC) of IgGs has been studied by several authors . Some studies have demonstrated that at around pH 6.5 the IgG antigen‐binging capacity in milk and cheese whey is partially maintained, even after pasteurisation conditions (72°C, 16 s) and that at mild temperatures (35–37°C) ABC is not affected .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperimmunised bovine milk and whey: influence of pH and enzymatic treatments on the antigen‐binding capacity of immunoglobulin G

Menéndez

Riera

2015

J Sci Food Agric

View full text Add to dashboard Cite

show abstract

Section: Resultssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Hyperimmunised bovine milk and whey: influence of pH and enzymatic treatments on the antigen‐binding capacity of immunoglobulin G

Menéndez

Riera

2015

J Sci Food Agric

View full text Add to dashboard Cite

show abstract

“…For example, when preparing immunoglobulin G, to avoid the side effects of anti-complementary activity, one of the processing steps is the treatment at pH 4 with the presence of pepsin. It is proved that this treatment at acidic pH 4 is quite effective as a viral inactivation step for lipid-enveloped viruses (70,71). The potency of this method for lipid-enveloped virus inactivation ranges from 5 to 8 log 10 reduction.…”

Section: Incubation In Acidic Phmentioning

confidence: 96%

Virus Reduction of Human Plasma-Derived Biological Medicines

Nazari

Jalili

Shahabi

et al. 2017

Jundishapur J Nat Pharm Prod

View full text Add to dashboard Cite

Context: Biological plasma-derived medicines play an important role in the treatment and also prevention of many diseases. The technique implemented to produce such medicines should ensure to minimize the risk of pathogen infection. A very crucial step is the removal or inactivation of highly pathogenic plasma viruses, and only achieving the highly pure product is not adequate. Evidence Acquisition: In the current study, a wide range of physical, chemical, and physicochemical methods of virus inactivation and virus removal were studied to minimize the virus contamination risk in plasma-derived medicines. Results: The virus removal or virus inactivation procedures showed that they were the quite effective techniques in pathogen reduction. But, some of these methods such as solvent/detergent were only effective on lipid-enveloped viruses, while other techniques can be effective both for lipid-enveloped and non-enveloped viruses. Conclusions: To inactivate or remove the most range of viruses, at least 2 different virus inactivation or virus removal techniques should be implemented. But, still emerging new pathogens cause a serious challenge in terms of blood safety, and consequently, safety of human plasma-derived medicines.

show abstract

“…A balance of degree of inactivation desired and product instability should be considered when selecting this target pH. 117 Similarly, duration of hold in the low pH medium (typically an hour) is critical for achieving robust inactivation but must be controlled to minimize product degradation. The buffer species used in preparing the low pH media also may play a role in determining the degree of inactivation, with superior performance observed using acetate buffer.…”

Section: Virus Inactivation Stepdlow Ph Treatmentmentioning

confidence: 99%

“…No effect of low pH treatment on glycosylation profiles was observed for multiple IgMs. 117 Chung et al 149 reported acceleration of a degradation event caused by antibody disulfide reduction at low pH, a phenomenon in mAb production attributed to the reducing enzymes from CHO cells during the harvest process as described in the Introduction. High fragment levels were observed during production of an IgG2 mAb due to antibody reduction in the harvested cell culture fluid.…”

Section: Impact Of Low Ph Hold Step On Protein Stabilitymentioning

confidence: 99%

Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy

Das

Narhi

Sreedhara³

et al. 2020

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The success of biotherapeutic development heavily relies on establishing robust production platforms. During the manufacturing process, the protein is exposed to multiple stress conditions that can result in physical and chemical modifications. The modified proteins may raise safety and quality concerns depending on the nature of the modification. Therefore, the protein modifications potentially resulting from various process steps need to be characterized and controlled. This commentary brings together expertise and knowledge from biopharmaceutical scientists and discusses the various manufacturing process steps that could adversely impact the quality of drug substance (DS). The major process steps discussed here are commonly used in mAb production using mammalian cells. These include production cell culture, harvest, antibody capture by protein A, virus inactivation, polishing by ion-exchange chromatography, virus filtration, ultrafiltration-diafiltration, compounding followed by release testing, transportation and storage of final DS. Several of these process steps are relevant to protein DS production in general. The authors attempt to critically assess the level of risk in each of the DS processing steps, discuss strategies to control or mitigate protein modification in these steps, and recommend mitigation approaches including guidance on development studies that mimic the stress induced by the unit operations.

show abstract

Immunoglobulins M Survive Low-pH Conditions Used for Virus Inactivation and for Elution from Bioaffinity Columns

Cited by 7 publications

References 31 publications

Hyperimmunised bovine milk and whey: influence of pH and enzymatic treatments on the antigen‐binding capacity of immunoglobulin G

Hyperimmunised bovine milk and whey: influence of pH and enzymatic treatments on the antigen‐binding capacity of immunoglobulin G

Virus Reduction of Human Plasma-Derived Biological Medicines

Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy

Contact Info

Product

Resources

About