In silico process characterization for biopharmaceutical development following the quality by design concept. (5th August 2021)

• Record Type: Journal Article
• Authors: Saleh, David; Wang, Gang; Rischawy, Federico; Kluters, Simon; Studts, Joey; Hubbuch, Jürgen
• Is Part Of: Biotechnology progress. Volume 37:Number 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-05
• Subjects: antibody purification -- cation exchange chromatography -- in silico process characterization -- mechanistic chromatography modeling; Biotechnology -- Periodicals; Food industry and trade -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/btpr.3196
• Languages: English
• ISSNs: 8756-7938

Abstract

Abstract: With the quality by design (QbD) initiative, regulatory authorities demand a consistent drug quality originating from a well‐understood manufacturing process. This study demonstrates the application of a previously published mechanistic chromatography model to the in silico process characterization (PCS) of a monoclonal antibody polishing step. The proposed modeling workflow covered the main tasks of traditional PCS studies following the QbD principles, including criticality assessment of 11 process parameters and establishment of their proven acceptable ranges of operation. Analyzing effects of multi‐variate sampling of process parameters on the purification outcome allowed identification of the edge‐of‐failure. Experimental validation of in silico results demanded approximately 75% less experiments compared to a purely wet‐lab based PCS study. Stochastic simulation, considering the measured variances of process parameters and loading material composition, was used to estimate the capability of the process to meet the acceptance criteria for critical quality attributes and key performance indicators. The proposed workflow enables the implementation of digital process twins as QbD tool for improved development of biopharmaceutical manufacturing processes.