Quality-by-Design (QbD) process evaluation for phytopharmaceuticals on the example of 10-deacetylbaccatin III from yew

Abstract

The focus of pharmaceutical product development lies on assuring excellent product quality at the endof a cost-efficient process. The Quality-by-Design (QbD) concept shifts the focus from quality assurancethrough testing to quality control by process understanding, resulting in very robust processes with highquality product. QbD was originally intended by authorities for biologics, where product quality provencompletely by analytics is not desired. Product quality has to be controlled by means of appropriateprocesses and operations as well.These demands were developed in order to improve patients’ safety by optimal drug quality at moreefficient manufacturing processes reducing costs for healthcare systems. Furthermore, production of biologicsincludes feedstock variability and complex multi-step manufacturing processes in batch operationwith variable lots – condition, which apply to botanicals as well.The use of rigorous (physico-chemical) process modeling in combination with QbD results in a highdegree of process understanding. This offers, contrary to popular prejudices, great benefit for manufacturerswith little extra effort during development.The methodical QbD-based approach is pursued to develop a process for extraction and purification of10-deacetylbaccatin III from yew needles. A short history and key elements of the QbD-based applicationare introduced.