Quality by Design (QbD), Biopharmaceutical Manufacture

The main concepts of the quality by design (QbD) initiative and applicability to biomanufacturing are described. QbD can lead to a future where product quality will be assured by flexible, science-based approaches. QbD is an umbrella of related concepts and approaches that include quality target product profiles, risk assessments, design spaces, control strategies using process analytical technology, continuous process improvement and others. We will also discuss the regulatory structure supporting the QbD initiative, including the International Conference on Harmonization Quality documents ICH Q8(R1) (Pharmaceutical Development), ICH Q9 (Risk Assessments), ICH Q10 (Quality Systems) and FDA's Process Analytical Technology (PAT) Guidance. A case study is presented for applying QbD to a biopharmaceutical process, viral clearance by anion exchange chromatography. It is believed that QbD will lead to more flexible processes which are justified based on risk and science rather than on a solely empirical approach. Keywords: QbD; ICH; biopharmaceutical development; risk management; design space; PAT; anion exchange chromatography