Risk assessment for biopharmaceutical single-use manufacturing: A case study of upstream continuous processing

Area of Science:

• Biotechnology
• Process Engineering
• Pharmaceutical Manufacturing

Background:

• The shift towards intensified upstream processing necessitates evaluating risks of single-use systems (SUS) in perfusion cultures.
• Traditional risk assessments often overlook the unique challenges of long-duration, high-titer perfusion processes compared to fed-batch cultures.

Purpose of the Study:

• To assess and compare the risks associated with implementing upstream single-use technology in fed-batch versus perfusion cell cultures.
• To identify specific high-risk components and operational differences between fed-batch and perfusion SUS for biomanufacturing.

Main Methods:

• Utilized Failure Modes and Effects Analysis (FMEA) to systematically evaluate risks in upstream single-use systems.
• Employed a simulated model process and an analytical method to quantify the impact of parameters on SUS specifications for objectivity.

Main Results:

• Many risks were comparable between fed-batch and perfusion SUS, but significant differences emerged in high-risk areas like daily sampling and system installation.
• Risk drivers differed, with larger bioreactors posing challenges for fed-batch and longer run times for perfusion cultures.

Conclusions:

• The FMEA method effectively identifies risks and informs control strategies for SUS in both fed-batch and perfusion processes.
• This risk assessment provides a foundation for developing holistic contamination control strategies and visualizing their efficacy in intensified bioprocessing.