Forced degradation studies of biopharmaceuticals: Selection of stress conditions

Tamizi, Elnaz; Jouyban, Abolghasem

doi:10.1016/j.ejpb.2015.10.016

Cited by 80 publications

(42 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Physical stability, chemical stability, and influences of different environmental factors are required for the biological activity of biopharmaceuticals, all of them should be evaluated using appropriate techniques . So we synthesized three isomers, GeXIVA[1,2], GeXIVA[1,3], and GeXIVA[1,4], using Fmoc chemistry, which were identified by RP‐UPLC and ESI‐MS.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the thiol group in the exposed Cys residues is a highly reactive functional group . Oxidation of Cys residues that could be catalyzed in alkaline conditions results in the formation of intra‐ and intermolecular disulfide bonds . For oxidation stability, although there is no large extent degradation compared with thermal stability, the degradation of the two isomers is obvious because the exposed Cys residues are sensitive to oxidation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of serum, enzyme, thiol, and forced degradation on the stabilities of αO‐Conotoxin GeXIVA[1,2] and GeXIVA [1,4]

et al. 2018

Chem Biol Drug Des

View full text Add to dashboard Cite

αO-conotoxin GeXIVA, which is a potent antagonist of α9α10 nicotinic acetylcholine receptor (nAChR), is of great interest as a potential analgesic for chronic neuropathic pain. It has three isomers, of which both GeXIVA[1,2] and GeXIVA[1,4] showed similar low nanomolar IC s in potent blocking rat α9α10 nAChRs. Here, we first reported stabilities of GeXIVA[1,2] and GeXIVA[1,4] in various biochemical circumstances, including human serum, enzymatic degradation, and thiol, which would be the key factors to affect stabilities of the two isomers in vivo. Simultaneously, forced degradation was carried out to evaluate stabilities of the two isomers. GeXIVA[1,2] and GeXIVA[1,4] were unstable when they were incubated in serum and digestive enzymes at 37°C. Their disulfide bond frameworks were easy to be scrambled in GSH and HSA. For different stress conditions, their stabilities were impacted greatly by oxidation, temperature, and alkaline conditions. The results may provide a foundation for storage conditions, structural modification, and pharmaceutical preparation of GeXIVA[1,2] and GeXIVA[1,4].

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of serum, enzyme, thiol, and forced degradation on the stabilities of αO‐Conotoxin GeXIVA[1,2] and GeXIVA [1,4]

et al. 2018

Chem Biol Drug Des

View full text Add to dashboard Cite

show abstract

“…Various methods are employed to generate such data including heating (Cheng et al, 2012; Hamrang et al, 2015), stirring (Luo et al, 2011; Sediq, Van Duijvenvoorde, Jiskoot, & Nejadnik, 2016), shaking (Kiese, Papppenberger, Friess, & Mahler, 2008; Rudiuk, Cohen‐Tannoudji, Huille, & Tribet, 2012), and simulation of transportation (Fleischman, Chung, Paul, & Lewus, 2017). The extent of aggregation, however, can be heavily dependent on the type of accelerated stress employed (Fleischman et al, 2017; Joubert, Luo, Nashed‐Samuel, Wypych, & Narhi, 2011; Tamizi & Jouyban, 2016). …”

Section: Introductionmentioning

confidence: 99%

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

Willis

Kumar

Dobson

et al. 2018

Biotech & Bioengineering

View full text Add to dashboard Cite

Monoclonal antibodies (mAbs) currently dominate the biopharmaceutical sector due to their potency and efficacy against a range of disease targets. These proteinaceous therapeutics are, however, susceptible to unfolding, mis‐folding, and aggregation by environmental perturbations. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation, and storage. Hydrodynamic forces have also been linked to aggregation, but the ability of different flow fields (e.g., shear and extensional flow) to trigger aggregation has remained unclear. To address this question, we previously developed a device that allows the degree of extensional flow to be controlled. Using this device we demonstrated that mAbs are particularly sensitive to the force exerted as a result of this flow‐field. Here, to investigate the utility of this device to bio‐process/biopharmaceutical development, we quantify the effects of the flow field and protein concentration on the aggregation of three mAbs. We show that the response surface of mAbs is distinct from that of bovine serum albumin (BSA) and also that mAbs of similar sequence display diverse sensitivity to hydrodynamic flow. Finally, we show that flow‐induced aggregation of each mAb is ameliorated by different buffers, opening up the possibility of using the device as a formulation tool. Perturbation of the native state by extensional flow may thus allow identification of aggregation‐resistant mAb candidates, their bio‐process parameters and formulation to be optimized earlier in the drug‐discovery pipeline using sub‐milligram quantities of material.

show abstract

“…[24,25] Some conditions mostly used for forced degradation studies are presented in Table1. [26,27] www.wjpps.com …”

Section: Degradation Conditionsmentioning

confidence: 99%

An Updated Review: Forced Degradation Study

Srivastavá¹

2017

WJPPS

View full text Add to dashboard Cite

Forced degradation is a powerful tool used routinely in pharmaceutical development in order to develop the stability indicating methods that lead to quality stability data and to understand the degradation pathways of the drug substances and drug products. The study ensures the appropriate stability of final pharmaceutical products in very early stages of pharmaceutical development. The forced degradation study is an essential step in the design of a regulatory compliant stability program for drug and formalized as a regulatory requirement. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms and also describes the analytical methods helpful for the development of stability indicating method.

show abstract

Forced degradation studies of biopharmaceuticals: Selection of stress conditions

Cited by 80 publications

References 112 publications

Effects of serum, enzyme, thiol, and forced degradation on the stabilities of αO‐Conotoxin GeXIVA[1,2] and GeXIVA [1,4]

Effects of serum, enzyme, thiol, and forced degradation on the stabilities of αO‐Conotoxin GeXIVA[1,2] and GeXIVA [1,4]

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

An Updated Review: Forced Degradation Study

Contact Info

Product

Resources

About