Flexible Design and Nimble Systems Help Prepare for a Biomedical Emergency

Flexible design and nimble systems help prepare for a biomedical emergency

A global specialty biopharmaceutical company entered into a public-private contract worth $220 million with the Biomedical Advance Research and Development Authority (BARDA) in 2012. Its primary goal was to establish a Center for Innovation in Advanced Development and Manufacturing (CIADM) to address challenges encountered in developing biodefense medical countermeasures.

One component of the CIADM’s vision was an expansion of the client’s facility to provide flexible vaccine manufacturing capabilities. The investment came as part of a private-public partnership with BARDA to establish the client’s facility as one of three new CIADMs to develop and manufacture vaccines and medical countermeasures according to its own mission and business objectives on a day-to-day basis.

If a public health crisis arose, each CIADM needed to transition from normal operations to emergency production mode and provide surge manufacturing to address the crisis. The client had to produce at least 50 million doses of pandemic influenza vaccine within four months.

The existing facility was a 32,000-square-foot, three-story structure. Expansion to the facility added 64,000 square feet of manufacturing, administrative, quality and warehouse space. While the production processes were being developed, the client proceeded with the design and construction of a multi-process manufacturing space. CRB met the demanding criteria of a multi-platform, multi-product and multi-scale manufacturing facility—along with the client’s desire to maximize the utilization of capital investments such as equipment, space and utilities— by designing a flexible facility that is easily reconfigurable between campaigns.

To address the various scale and types of processes, equipment pieces were carefully selected and sized to create a broad process envelope. The expression systems were as follows:

  • 500-liter microbial
  • 2,000-liter monoclonal antibody
  • 2,000-liter insect cell/baculovirus
  • 2,000-liter mammalian cells/virus propagation

There were numerous production technologies and regulatory considerations:

  • NIH BSL-2 containment
  • Intra- and extra-cellular product recovery and purification
  • Open and closed processing unit operations
  • Hybrid process equipment approach of portable process stations with fixed stainless-steel equipment and single-use systems
  • Process suites configurable for multiple products and scales

The open processing unit operations and BSL-2 containment requirements created an interesting twist to the notion of flexible facility design. Industry trends and CRB’s FutureFacility™ concept approach move toward flexible facility design with open ballrooms and minimal segregation based on closed processing. Being flexible with the client’s project parameters and ranges meant physical segregation of various operations, air classification, gowning and airlock transitions that allowed the option to run open processes provide BSL-2 containment. The layout provided five adjacent process suites that provided cell+/cell-, virus+/virus-, and open- or closed-processing segregation.

In addition to the architectural considerations, CRB paid close attention to the design of utility generation and distribution systems. Generation systems were sized to account for large swings in utility usage with turndown capability provided to improve efficiency. The distribution of critical process utilities maximized flexibility by allocating utility drops at areas that could accommodate the various process scenarios. These interchangeable utility stations allowed for plug-and-play operation, allowing the client to move equipment in and out of the space in rapid response to production demands.

The client’s desire for flexibility required a layered design approach that accounted for these goals:

  • Conceptual design focused on layout development, factoring in equipment move-in paths, multiple equipment arrangements and physical segregation of spaces
  • Basic design focused on right-sizing the process and process utility systems to meet varying demands while maximizing operating efficiencies
  • Detailed design focused on leveraging distribution of systems throughout the space and ensuring final design accounted for multiple operating scenarios

This careful examination and prepared approach resulted in an adaptable facility built to accommodate the client’s developing business needs while also meeting rigorous demands established by BARDA in the event of pandemic declaration, all within established industry costing benchmarks.

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