Pandemic threat protection in a biotech facility
Emergent BioSolutions Inc.’s new manufacturing facility is designed to be flexible and responsive, ready to ramp up production at life-saving speed to stop emerging pandemic threats.
Responding locally to a world of global pandemic threats
Terror threats leveraging biological weapons like anthrax and global health events like the influenza A virus subtype H1N1, severe acute respiratory syndrome (SARS) and COVID-19 (coronavirus) outbreaks pose a considerable and ever-increasing risk. As a primary supplier of the anthrax vaccine, Emergent has been at the forefront of the United States’ efforts to defend Americans for almost 15 years. This track record led the Biomedical Advanced Research and Development Authority (BARDA) to partner with Emergent to establish the Center for Innovation in Advanced Development and Manufacturing (CIADM).
Emergent BioSolutions, Inc.
BARDA, within the Office of the Assistant Secretary for Preparedness and Response in the US Department of Health and Human Services, exists for the sole purpose of providing integrated, systemic approaches to the development and purchase of the necessary vaccines, drugs, therapies and diagnostic tools for public health medical emergencies.
Emergent’s CIADM facility is one of only three facilities in the US with rapid development and manufacturing capabilities to respond to a global influenza pandemic. The CIADM is equipped to:
- Manufacture, test and release 50 million doses of novel pandemic flu vaccine in its final dosage form within four months of pandemic threats
- Produce a total of 100 million doses within six months of declaration
CRB provided the process expertise and BARDA experience to design and build this facility capable of producing a determined number of pandemic flu vaccine doses within a four-month campaign window.
Emergent's BARDA facility represents a model of the facility of the future
Emergent’s BARDA CIADM is the facility of the future
The facility is ready to respond to demands from both known and unknown pandemic threats.
It’s highly adaptable to fluctuations in capacity demand that could arise from pandemics with the recent addition of 4,000-liter bioreactors.
It’s highly flexible with the capability to process cell culture, microbial and viral hosts.
The facility offers the potential to plug or remove necessary unit operations to match any potential process.
And finally, the CIADM represents a unique partnership between biotech and the government that delivers countermeasures to life-threatening situations and significant public health threats.
Designing for future pandemic threats
The combination of BARDA’s requirements for rapid production of novel vaccines in response to pandemic threats with Emergent’s own shifting internal pipeline took the complex challenge of flexible facility design to an entirely new level. Our team had to design a facility that’s suitable for multi-platform, multi-process and multi-scale production. It also required rapid changeover and short ramp-up time from a steady state to pandemic response production.
To account for this spectrum of process demands, the project team focused efforts on creating spaces flexible enough to meet a core set of process requirements with varying levels of contingency. At the time of design, the systems considered for the production of a pandemic influenza vaccine were:
- 500-liter microbial fermentation
- 2,000-liter insect cell/baculovirus
- 2,000-liter mammalian cells/virus propagation
“With the expansion of our Bayview campus, Emergent is pleased to directly support BARDA’s vision of enhancing the nation’s capability to respond quickly to both known and emerging public health threats. This milestone strengthens our manufacturing infrastructure and symbolizes Emergent’s commitment to the city of Baltimore and the state of Maryland, where we are proud to meaningfully contribute to economic activity and job growth.”
Daniel J. Abdun-Nabi, President and CEO of Emergent
Equipment technology selection
A common trend in future facilities is the widespread adoption of single-use technology. While the benefits of this technology are well-publicized (reduction in utility demands, facility footprint, changeover time, etc.), a flexible manufacturing facility is not necessarily a single-use one. The Emergent project team was very selective when adopting single-use technologies based on the various processes.
Equipment was categorized as fixed, movable or portable:
- Fixed equipment has a dedicated footprint and will be kept in place regardless of product campaign, whereas portable and movable equipment are dependent on selected product campaign and can be adjusted accordingly.
- Movable equipment can be moved in and out depending on process needs but, for the most part, will be kept in place across multiple operations.
- Portable equipment facilitates the movement of process and product transfer.
Upstream applications naturally lend themselves to single-use systems due to the ability to change over quickly between campaigns and eliminate the need for time-consuming CIP and SIP operations. This same logic was applied to product collection systems.
Due to the facility scale, available single-use technology for downstream systems was limited.
However, our team designed each system with integral cleaning functionality to eliminate the need for a centralized CIP system and associated distribution piping.
Selecting media and buffer prep equipment balanced cleaning demands versus process flexibility. We designed the buffer prep systems to be stainless steel since the accepted cleaning protocol of HWFI rinse is less onerous or time consuming. We originally designed the media prep systems to be single-use to reduce cleaning burden; however, the potential need of heat inactivation pushed us to reconsider and change to a stainless steel approach. Adopting the same mindset as downstream process equipment, we designed the media tanks with a dedicated CIP pump and self-cleaning capabilities.
The entire equipment selection process was directly tied to achieving a full range of long-term flexibility with a focus on changeover time and efficiency.
Pandemic flu vaccine production
ONEsolution™ provides flexibility throughout the project
Despite careful contingency planning, changes to the original design and scope of a project are often inevitable. The BARDA-Emergent expansion project had three significant design changes during its execution. The first two involved economizing on build-out costs (pausing the fit-out of office space until staffing caught up) and specifying a new and more efficient chilled water system to service both existing and new buildings on the campus and save on, among other things, long-term energy-related operating costs.
The change process demonstrated not only the flexibility of the original design to accommodate a range of possible processes, but also the benefit of working with one unified team through CRB’s ONEsolution approach. Integrating the construction team earlier in the process decreased the disruption that changes could cause.
Furthermore, institutionalized experience and a formal risk management program allowed the design, engineering and construction team members to integrate best-practice project management. Additionally, our team could draw on deep, shared experience and mitigate pain points with robust processes. All team members were co-located on site, which helped the project establish a culture dedicated to the project’s efficient execution, cost containment, change and quality. Ultimately these project ethics contributed to zero lost time injury reports over the 239,872-hour duration of the project.
Purification 2, a room for processes that require a final viral clearance step, illustrates the collaboration between design and construction on this project. It was initially constructed as a shell space to provide necessary flexibility because the equipment design had not been finalized. With the shell in place, the equipment installation could happen further along in construction. This prevented delays to the overall project progress.
A facility fit to face the future
In conceptualizing and engineering one of the first CIADM facilities, Emergent defined a new type of facility: an emerging biotech facility operationally agile enough to quickly campaign products in and out with minimal limitations. The project’s iterative design process was instrumental in delivering the flexible, responsive process-agnostic platform that BARDA demanded while still providing Emergent with a facility to meet internal needs.
During the project, Emergent responded to two separate task orders from BARDA–one in response to the Ebola outbreak of 2014 and one for the rapid deployment of an in-development ZIKA virus vaccine. Emergent’s existing pilot plant and clinical CGMP production capabilities demonstrated that rapid development and large-scale manufacturing of these products was feasible within the CIADM facility. Emergent also quickly adapted the facility to account for internal business needs, including the company’s acquisition of GSK’s FDA-approved anthrax medicine. The flexible nature of the facility will allow for the installation of new bioreactors with minimal modifications to utility distribution systems and no necessary changes to building architecture, structure, or infrastructure.
The project illustrates how CRB’s successful ONEsolution approach and operational concepts help companies seeking to develop reliable capacity on demand, ready to manage a range of uncertainties and risks. Emergent’s CIADM Bayview expansion is a highly dynamic facility equipped to meet the demand for pharmaceuticals in response to a pandemic. It is also our model of a facility designed and constructed for the future of biopharmaceutical manufacturing.