Abstract:
:Robust higher order structure (HOS) characterization capability and strategy are critical throughout biopharmaceutical development from initial candidate selection and formulation screening to process optimization and manufacturing. This case study describes the utility of several orthogonal HOS methods as investigational tools during purification process development. An atypically high level of residual detergent in a development drug substance batch of a therapeutic monoclonal antibody triggered a root cause investigation. Several orthogonal biophysical techniques were used to uncover and characterize a specific interaction between the detergent and the antibody. Isothermal titration calorimetry (ITC) was used to quantify the molar ratio and affinity of the binding event, and circular dichroism (CD) spectroscopy and differential scanning calorimetry (DSC) were used to evaluate corresponding impacts on secondary/tertiary structure and thermal stability, respectively. As detergents are used routinely in biopharmaceutical processing, this case study highlights the value and power of HOS data in informing technical investigations and underlines the importance of HOS characterization as a component of overall biopharmaceutical analytical control strategy.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Budyak IL,Doyle BL,Weiss WF 4thdoi
10.1002/jps.24293subject
Has Abstractpub_date
2015-04-01 00:00:00pages
1543-7issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30178-7journal_volume
104pub_type
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