The importance of critical quality attributes in Quality by Design for rapid bioprocess development strategies
QbD and PAT could revolutionise the way biopharma industries operate by cutting down their attrition rates, which could drastically change their business model. This article considers the issues involved.
The pharmaceutical market is valued at $774bn and expected to reach $1.06tn by 2022.1 Biopharmaceuticals play an important role in this increase and their contribution is set to increase from 27% to 52% of world pharmaceutical sales, dominating the oncology and anti-rheumatics market until 2022, both in sales and R&D.1 Although the trends seem to be in favour of biopharmaceutical development, growth rates have not yet reached their full potential due to financial and technical complexities involved in the early stages of research and development, bioprocess development and preclinical testing.
Compared to the 21 biologics approved by the US Food and Drug Administration (FDA) in 2015, only 14 were approved in 2016, indicating a scarcity in innovation and lack of progress in bioprocess development strategies – mainly in early-stage screening and manufacturability. This, coupled with the looming second patent expiry cliff leading to the biosimilar boom, highlights a pressing need for rapid bioprocess development strategies and faster commercialisation. The aforementioned challenges are estimated to put around $200bn of sales at risk. Tackling these challenges will allow resources to be redirected into more innovation with a focus on drugs for rare and neglected diseases.
The need for Quality by Design (QbD) arose in early 2000, as the traditional approach to biopharmaceutical drug development was primarily empirical. This, combined with limited emphasis on process understanding, led to manufacturing failures and consequently increased product wastage. Furthermore, limited attention was given to the analysis of the root causes of these failures and to the prediction of scale-up effects on the final product quality and yield. Unlike conventional drugs, which mainly revolve around small-molecule chemistry, biological drugs are far more complex to produce and characterise as they are 200-1,000 times larger, structurally more complex and highly sensitive to their manufacturing conditions. The costs involved in development and production of biopharmaceutical entities are 1.5-2.5 times higher than that of small molecule drugs.2
The QbD paradigm
The concept of QbD was incorporated into the pharmaceutical manufacturing control review process in 2004, following the pharmaceutical cGMP for the 21st-century initiative (Figure 1). The main aim of the initiative was to…