Development of a comprehensive approach for performance evaluation of a quantitative multi-attribute method as a
Eriko Numao1, Kumi Yanagisawa2, Mayu Hosono2
1Bio Process Research and Development Laboratories, Production Division, Kyowa Kirin Co., Ltd., Takasaki, Gunma, 370-0013, Japan. eriko.numao.jc@kyowakirin.com.
Summary
The multi-attribute method accurately quantifies therapeutic protein post-translational modifications (PTMs). Comparing calculation formulas showed minimal differences, validating its reliability for PTM analysis.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Pharmaceutical Science
Background:
- Therapeutic proteins often undergo post-translational modifications (PTMs) that impact their efficacy and safety.
- Accurate quantification of PTMs is crucial for quality control and characterization of biopharmaceuticals.
- The multi-attribute method (MAM) offers a site-specific and spontaneous approach for evaluating multiple protein attributes.
Purpose of the Study:
- To evaluate the reliability of the multi-attribute method (MAM) for quantifying post-translational modifications (PTMs) in therapeutic proteins.
- To compare PTM abundance calculations using different formula types.
- To assess the suitability of internal standards (ISs) for method validation and system suitability testing in mass spectrometry (MS).
Main Methods:
- Comparison of PTM abundance calculations derived from three distinct formula types.
- Utilized two distinct peptide types as internal standards (ISs) for method evaluation.
- Employed one IS as a 'standard peak' to establish mass spectrometry (MS) signal strength and performed system suitability tests using IS recovery rates.
Main Results:
- Calculated PTM abundances showed negligible differences across the three formula types, indicating robustness.
- Internal standards effectively facilitated method evaluation and system suitability testing.
- A defined limit of quantification relative to IS ensures consistent MS intensity thresholds across detected peaks.
Conclusions:
- The multi-attribute method (MAM) provides a reliable and consistent approach for quantifying post-translational modifications (PTMs) in therapeutic proteins.
- The use of internal standards is effective for validating MAM performance and ensuring mass spectrometry (MS) system suitability.
- This validated method enables accurate and sensitive detection of minor components and PTMs in biopharmaceutical analysis.
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