MIT CAACB Risk Assessment Case Study: Assessing Virus Cross-Contamination Risk between Two Simultaneous Processes in...

Area of Science:

• Biopharmaceutical Manufacturing
• Quality Risk Management
• Viral Contamination Control

Background:

• Industry interest is growing in open ballroom manufacturing with closed systems.
• Previous work established quality risk management (QRM) for viral contamination in cell culture.
• This study applies QRM principles to novel manufacturing modalities.

Purpose of the Study:

• To conduct a case study assessing viral cross-contamination risks in an open manufacturing facility.
• To demonstrate leveraging risk management for risk assessment in new manufacturing approaches.
• To evaluate viral risk between human (HEK-293) and non-human (CHO) host cell systems.

Main Methods:

• Followed the International Council for Harmonisation (ICH) quality risk management workflow.
• Included process mapping, risk question definition, risk evaluation, and risk control.
• Utilized a Failure Mode and Effects Analysis (FMEA) for detailed risk identification and reduction planning.

Main Results:

• Assessed viral cross-contamination risks in a simultaneous recombinant protein production scenario.
• Focused on contamination of downstream filtration (Process 2) from an undetected bioreactor virus (Process 1).
• Identified specific risks and proposed corresponding risk reduction actions via FMEA.

Conclusions:

• Quality risk management is applicable to assessing viral contamination in open biomanufacturing.
• The case study provides a practical framework for risk assessment in advanced manufacturing.
• Methodologies like FMEA are crucial for identifying and mitigating contamination risks.