As the industry challenges past assumptions and approaches, evolving technologies and operational practices are enabling lower
cost and more flexible facilities while the highest standards of product quality and patient safety are maintained. The understanding
of what it takes to achieve and demonstrate closed- and functionally closed systems is allowing ballroom or open-production
halls to be employed so that build costs and ongoing operating expenses are lower. Risk-management strategies are being rigorously
used to eliminate and mitigate potential product contamination from planned and unplanned breaches in multi-product concurrent
The reliance on clear and well thought out design and operating principles has been described. These key design and operating
requirements include procedural controls, spatial and temporal segregation controls, and increased use of automation. The
additional complexity and reliance on human factors from logistical segregation as opposed to physical segregation has been
discussed. The added importance of contamination detection and control has been set out.
Not all considerations suggested are applicable in all situations, and many options exist within current and new facility
designs to adopt these concepts. However, opportunities do exist to reduce area classification for specific operations or
the consolidation of manufacturing processing areas to gain the benefits of flexible, low-cost biomanufacturing.
The authors would like to thank Marc Pelletier (CRB Engineers) who is leading initiatives via the ASME BPE and ISPE for helping
us with the definitions section and for providing valuable comments generally. They would also like to thank Steve Buchholz
(Gallus Biopharmaceuticals), Martyn Becker, Joe Rogalewicz (GSK), Beth Junker (Merck) and Teresa Feeser (BMS) for providing
feedback on the draft.
Simon Chalk is director, BioPhorum Operations Group, firstname.lastname@example.org
; Scott Probst is group head, healthCare and biotechnology, technology development, process design and optimization, Bayer Technology
Services; Ken Green is director, global manufacturing services, Pfizer, Inc.; Russell Moser is validation manager, Janssen Biopharmaceuticals; Frank Urbanski is director, global engineering, Pfizer Inc.; Matthew Zicaro is an HVAC engineer; Paul Smock is senior director, technical quality, MedImmune; Larry Pranzo is associate director architect/engineer, global engineering, Merck; Liz Dooley is engineering director, Janssen Supply Chain, Ireland; Phil McDuff is senior director, Engineering, Biogen Idec.
1. Chalk, S., et.al., BioPharm. Intl. 24(8) (August 2011).
2. ICH, Q9 Quality Risk Management (ICH, November 9, 2005).
3. ISPE, GAMP 5: A Risk-Based Approach to Compliant GxP Computerized Systems (ISPE 2007).