Continuous biomanufacturing in upstream and downstream processing

Abstract

Continuous bioprocesses have become a significant technological change in regulated industries, with process analytical technology (PAT) and quality-by-design (QbD) being essential for enabling continuous biomanufacturing. PAT and QbD are associated with process automation and control, providing real-time key process information. Continuous manufacturing eliminates hold times and reduces processing times, providing benefits such as improved product quality, reduced waste, lower costs, and increased manufacturing flexibility and agility. Over the past decade, advancements in science and engineering, along with the adoption of QbD and the advancement of PAT, have progressed the scientific and regulatory readiness for continuous manufacturing. Regulatory authorities support the implementation of continuous manufacturing using science- and risk-based approaches, providing a great deal of potential to address issues of agility, flexibility, cost, and robustness in the development of pharmaceutical manufacturing processes.

Digital Twin for Continuous Production of Virus-like Particles toward Autonomous Operation

“…Real-time predictions of quality attributes through process models enable continuous optimization, even after submission. 34 To enable continuous production of VLPs, a bioreactor system is required that gently retains the shear-sensitive cells 11,43,44 while removing the product from the reactor. 45 Various systems are available for cell retention of animal cells, including membrane-based systems such as ATF and TFF as well as density difference-based systems such as settlers (inclined and acoustic) or hydrocyclones.…”

“…These can be made even more versatile by adding heterologous envelope proteins, such as the S protein of SARS-CoV-2. As these are enveloped VLPs, precise process control with minimal holding times is essential …”

“…To overcome these challenges, QbD methods link process parameters to product quality characteristics. QbD-based process development is increasingly becoming the standard in the biopharmaceutical industry and is required by regulatory authorities. ,, A comprehensive control strategy is essential to achieving the desired quality target product profile. Validated process models can define design spaces to avoid out-of-specification (OOS) batches.…”

“…The holistic QbD approach ensures that product quality remains consistent from development to production. Real-time predictions of quality attributes through process models enable continuous optimization, even after submission …”

“…As these are enveloped VLPs, precise process control with minimal holding times is essential. 34 HIV belongs to the retrovirus family and is a lentivirus that causes, upon infection, the acquired immunodeficiency syndrome (AIDS). Individuals with AIDS are more susceptible to fatal opportunistic infections.…”