Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles

Abstract

The concept of design space has been taking root under the quality by design paradigm as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. This paper outlines the development of a design space for a hydrophobic interaction chromatography (HIC) process step. The design space included the impact of raw material lot-to-lot variability and variations in the feed stream from cell culture. A failure modes and effects analysis was employed as the basis for the process characterization exercise. During mapping of the process design space, the multi-dimensional combination of operational variables were studied to quantify the impact on process performance in terms of yield and product quality. Variability in resin hydrophobicity was found to have a significant influence on step yield and high-molecular weight aggregate clearance through the HIC step. A robust operating window was identified for this process step that enabled a higher step yield while ensuring acceptable product quality.

Aggregates in monoclonal antibody manufacturing processes

“…The application of the QbD during process development phase helps to develop a suitable process control strategy for those quality attributes that are considered critical. For aggregate removal, the application of QbD in the development of the hydrophobic interaction chromatography has been successfully proved by Jiang et al (2010). The manufacturing process of a biotechnological product, however, is a complex multi-step process where aggregation can be caused during different stages of the process.…”

Optimization of a chromatographic process for the purification of saponins in Panax notoginseng extract using a design space approach

“…Recently, Quality by Design (QbD) and design space concept are gained increasing popularity in pharmaceutical manufacturing process, such as ethanol precipitation [17,18], powder blending [19], tablet manufacturing [20], pharmaceutical co-precipitation [21] and chromatographic process [22][23][24][25]. The application of http://dx.doi.org/10.1016/j.seppur.2015.09.035 1383-5866/Ó 2015 Elsevier B.V. All rights reserved.…”

“…Using statistical model is an alternative way. Recently, Jiang et al [23] and Ji et al [24] have applied QbD principles to develop and optimize chromatographic process for protein purification. Process critical quality attributes (CQAs) and critical process parameters (CPPs) were identified and design spaces were mapped.…”

Methods and Tools for Robust Optimal Control of Batch Chromatographic Separation Processes

“…Process characterization is conducted to identify the impact of process parameters on the products CQA's [8], which is then used to define a process design space. A design space is defined as "the multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide an assurance of product quality" [9].…”