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2021, Number 1

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Biotecnol Apl 2021; 38 (1)

A continued process verification strategy at first stages of monoclonal antibody purification by integrated risk assessment and multivariate data analysis

Toledo RA, Gozá LO, Hernández LE, Leonard RI, Hidalgo MG

Language: English
References: 25
Page: 1201-1208
PDF size: 724.10 Kb.


ABSTRACT

According to current regulatory expectations, continued process verification (CPV) must guarantee post-qualification monitoring of critical process parameters (CPP). Such parameters are not easy identifiable in biotechnological processes given its inherent complexities. Therefore, this work was aimed to bring methods for an effective determination of CPP thus providing the necessary groundwork for elaborating a CPV strategy. Knowledge and experience accumulated along the lifecycle of a legacy monoclonal antibody product were applied, focusing on its first stages of downstream purification. Process parameters defined for analysis were ranked through a cause-effect risk matrix and criticality levels deduced using Pareto distribution. Subsequently, data from three consecutive production campaigns were processed by the principal component analysis (PCA) method for a comprehensive characterization of process variability, as well as clusters analysis and soft independent modeling of class analogy (SIMCA) methods for differentiating operational modes among campaigns. A set of 13 process parameters were confirmed as CPP, given its major impact on process variability, while the remaining five were considered as key operating parameters (KOP). Such outcome, achieved theoretically, was corroborated with process actual operational incidences, contributing to elaborate a well-founded monitoring plan for assuring CPV and its viable execution.


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