Working within the Design Space: Do Our Static Process Characterization Methods Suffice?

Pharmaceutics

卷:12

Sandrine Dessoy¹  Matthew Sanders¹  Annick Vandercammen¹  Christos Varsakelis¹  Marco Mariti¹  Alexander Pysik¹  Geoffroy Geldhof¹  Moritz von Stosch¹  René Schenkendorf² 

[1] GSK, B-1330 Rixensart, Belgium;

[2] Institute of Energy and Process Systems Engineering, TU Braunschweig, 38106 Braunschweig, Germany;

关键词: process analytical technology;    quality by design;    dynamic design space;    reachability;    flexibility;    dynamic modeling;   

DOI  :  10.3390/pharmaceutics12060562

来源: DOAJ

【 摘 要 】

The Process Analytical Technology initiative and Quality by Design paradigm have led to changes in the guidelines and views of how to develop drug manufacturing processes. On this occasion the concept of the design space, which describes the impact of process parameters and material attributes on the attributes of the product, was introduced in the ICH Q8 guideline. The way the design space is defined and can be presented for regulatory approval seems to be left to the applicants, among who at least a consensus on how to characterize the design space seems to have evolved. The large majority of design spaces described in publications seem to follow a “static” statistical experimentation and modeling approach. Given that temporal deviations in the process parameters (i.e., moving within the design space) are of a dynamic nature, static approaches might not suffice for the consideration of the implications of variations in the values of the process parameters. In this paper, different forms of design space representations are discussed and the current consensus is challenged, which in turn, establishes the need for a dynamic representation and characterization of the design space. Subsequently, selected approaches for a dynamic representation, characterization and validation which are proposed in the literature are discussed, also showcasing the opportunity to integrate the activities of process characterization, process monitoring and process control strategy development.

【 授权许可】

Unknown