Impact of Residual Impurities and Contaminants on Protein Stability

Wang, Wei; Arunkumar, A.I.; Thakkar, Santosh V.

doi:10.1002/jps.23931

Cited by 94 publications

(52 citation statements)

References 212 publications

(354 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, biosimilar comparison studies have to take into consideration the variability of the impurity profiles of the different batches. 54,55 …”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms

Mozziconacci

Okbazghi

et al. 2016

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

As part of a series of papers in this special issue evaluating model IgG1-Fc glycoforms for biosimilarity analysis, three well-defined IgG1-Fc glycoforms (High mannose-Fc, Man5-Fc, GlcNAc-Fc), and a non-glycosylated Fc protein (N297Q-Fc) were examined in this work to elucidate chemical degradation pathways. The four proteins underwent a combination of accelerated thermal stability studies, and four independent forced degradation studies (UV-light, metal-catalyzed oxidation, peroxyl radicals, and hydrogen peroxide) at pH 6.0. Our results highlight chemical degradations at Asn315, Met428, Trp277, and Trp313. A cross-comparison of the different Fc glycoforms, stress conditions, and the observed chemical reactions revealed that both the deamidation of Asn315 and the transformation of Trp277 into glycine hydroperoxide were glycan-dependent during incubation for three months at 40°C. Our data will show that not only different glycans affect chemical degradation differently, but also do lead to different impurity profiles, which can affect chemical degradation.

show abstract

“…Therefore, biosimilar comparison studies have to take into consideration the variability of the impurity profiles of the different batches. 54,55 …”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms

Mozziconacci

Okbazghi

et al. 2016

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Drugs that are adequately freeze-dried (lyophilized) remain stable for several years, even when stored without refrigeration [28]; however, degradation can occur because of inadequate purification or lyophilization processes [34]. Additionally, there is evidence that the biological potency of eCG might be related to differences in the eCG titer of serum collected from pregnant mares [1].…”

Section: Discussionmentioning

confidence: 99%

“…These steps can introduce contaminants such as residual sanitizing agents, materials that leach from product contact surfaces, and contaminants from the environment of the production area [34]. Although many process-related impurities are routinely monitored, some types of contaminants, such as hormone-related forms, are generally not investigated, especially in the final product.…”

Section: Discussionmentioning

confidence: 99%

“…Although many process-related impurities are routinely monitored, some types of contaminants, such as hormone-related forms, are generally not investigated, especially in the final product. This is because the level of these contaminants in a drug product is often too low to be detected by traditional analytical methods, and does not lead to serious safety concerns [34]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Physical-chemical and biological characterization of different preparations of equine chorionic gonadotropin

et al. 2016

View full text Add to dashboard Cite

Ovarian stimulation with commercial preparations of equine chorionic gonadotropin (eCG) produces extremely variable responses in domestic animals, ranging from excessive stimulation to practically no stimulation, when applied on the basis of their declared unitage. This study was conducted to analyze four commercial preparations from different manufacturers via reversed-phase HPLC (RP-HPLC) in comparison with a reference preparation and an official International Standard from the World Health Organization. The peaks obtained by this qualitative and quantitative physical–chemical analysis were compared using an in vivo bioassay based on the ovarian weight gain of prepubertal female rats. The RP-HPLC data showed one or two peaks close to a main peak (tR = 27.9 min), which were related to the in vivo bioactivity. Commercial preparations that have this altered peak showed very little or no in vivo activity, as demonstrated by rat ovarian weight and in peripubertal gilts induced to ovulate. Overall, these findings indicate that RP-HPLC can be a rapid and reliable tool to reveal changes in the physicochemical profile of commercial eCG that is apparently related to decreased biological activity of this hormone.

show abstract

“…PEG impurities were considered to be involved in the crystallization and aggregate formation mechanisms Excipient impurities can affect the protein drug stability in a manifold manner. The presence of a particular impurity can result for example in acidification of the formulation, interface‐induced protein degradation, aggregation, oxidation, hydrolysis, or drug product adducts . Consequently, it was aimed to highlight the effects of certain PEG impurities on mAb1 crystallization and aggregate formation.…”

Section: Discussionmentioning

confidence: 99%

The “New Polyethylene Glycol Dilemma”: Polyethylene Glycol Impurities and Their Paradox Role in mAb Crystallization

Hildebrandt¹,

Joos²,

Saedler

et al. 2015

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Impact of Residual Impurities and Contaminants on Protein Stability

Cited by 94 publications

References 212 publications

Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms

Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms

Physical-chemical and biological characterization of different preparations of equine chorionic gonadotropin

The “New Polyethylene Glycol Dilemma”: Polyethylene Glycol Impurities and Their Paradox Role in mAb Crystallization

Contact Info

Product

Resources

About