Viral vector manufacturing—the process necessary for creating the crucial carriers that transport therapeutic genes to target cells—has become one of the most significant and innovative advancements in modern healthcare, such as with the creation of the COVID-19 vaccine.
The facility was designed to include host cell prep, multi-product, upstream/downstream viral vector suites with small-scale fill finish
The viral vector manufacturing market size was estimated to be worth more than $6 billion in 2023 and is projected to reach nearly $39 billion within the next decade. More than 25 viral vector-based gene therapy products have already been approved worldwide, with more than 200 viral vector-based gene therapy drug candidates undergoing clinical evaluation.
Yet given the complexities and nuances of this still-emerging field, the development and redevelopment of viral vector manufacturing sites present real-world challenges that require expert construction and oversight, including segregation and biosafety level requirements associated with the facilities.
The project: Manufacturing and QC operations
For one such project, global construction and development firm Skanska was hired by a global life science and clinical research company for a complex cleanroom project in suburban Boston.
Phase 1 of the project included the development of a new cGMP Manufacturing and QC Operations facility as an expansion of an existing 50,000 sqft shell building just outside of Boston.
Skanska and the process pipe subcontractor jointly developed the utility panel to have a removable face panel
Project parameters called for construction to meet Center for Disease Control guidelines for biosafety level 2+. The project included a self-contained, small-scale cGMP viral vector manufacturing operation embedded in an estimated 18,000 sqft build-out. The project also called for 14,500 sqft of supporting facility spaces housing all supporting utilities, infrastructure, and services to support a manufacturing operation.
The facility was designed to include host cell prep, multi-product, upstream/downstream viral vector suites with small-scale fill finish, along with the necessary manufacturing support and utilities. The project also called for the design of six viral manufacturing suites to operate independently and in a segregated manner from each other. Thus, allowing multiple viral vector products to be produced simultaneously in the different manufacturing suites.
Additionally, the suites were designed to operate as either upstream or downstream manufacturing areas, depending upon the manufacturing needs. Single-use technologies were incorporated into the design as much as possible. All viral suites, including the fill-finish, were decontaminated with vaporised hydrogen peroxide as part of the product changeover procedure.
The challenge: Non-walkable ceiling
One of the major challenges on this project was that the facility did not have a walkable ceiling due to the 14-foot floor-to-ceiling heights. This made coordination critical. During this phase, it was identified that the utility panels in the room would not be accessible from above for maintenance and final connections.
The innovative solution: Removable face panel
Structural, mechanical, electrical, and plumbing elements, as well as the design and age of any viral vector manufacturing facility, whether a new build, retrofit, or expansion, are all vital considerations when it comes to accommodating the appropriate biosafety and room classification requirements. Time and cost are also two standard considerations for any project.
To resolve the non-walkable ceiling issue at the facility, Skanska and the process pipe subcontractor jointly developed the utility panel to have a removable face panel that allowed users to make the necessary connection above the ceiling from the cleanrooms below.
Development of the utility panel allowed the project team to install the cleanroom ceiling panels during the normal flow of work and avoid leaving the ceiling out until the end of the project, providing the client with a safe and reliable method for maintaining their systems.
The team created a platform above the roof to solve for having no space to place their mechanical equipment
The fill-finish suite, the final phase where active ingredients are formulated, was designed to support up to 2,000 vials per batch. The vial debagging, filling, stoppering, and crimping steps were designed to take place within an integrated modular isolator manufactured by Bausch+Strobel with a single chamber, rigid glass panels, and an integrated VHP decontamination system.
The isolator was provided as a completely self-contained system, providing a controlled environment zone complying with Grade A air classification requirements.
The new cGMP manufacturing suites are served by new air handler units supplying 100% outside air. All air is exhausted through a HEPA filter bank. The new HVAC equipment was installed in a new 8,000-square-foot mechanical penthouse located above the offices on Level 2.
Facility coordination
With the new ceiling solution in place and finalised, the facility can now house state-of-the-art equipment in cleanroom suites specially designed to accommodate a broad-range of viral vector manufacturing process technologies. It boasts multiple drug substance suites able to support large-scale adherent and stirred tank production, an automated fill/finish system leveraging isolator technology, quality control laboratories, and process development space.
The facility was designed with an HVAC system for grade C cleanrooms, unidirectional flow, and a centralised vaporised hydrogen peroxide system to ensure suite sanitisation.
More cleanrooms are being renovated to meet updated regulations and energy efficiency measures
This site produces and tests viral vectors for gene and cell therapy with adherent and suspension cell culture processes, a variety of chromatography and filtration purification processes, and a state-of-the-art isolator and integrated fill system.
There were a few other challenges that had to be overcome throughout the facility’s construction. The team created a platform above the roof to solve for having no space to place their mechanical equipment, and given the project was in close proximity to a local airport, daily coordination was necessary when working on roof equipment installation. Skanska also designed future removable panels to address the need for installation of future equipment.
Lessons learned
Cleanroom technologies are used across the broader science and technology market where contamination is critical to product safety and quality. A controlled environment ensures sterile pharmaceuticals are safe for use on or in the human body, per the FDA’s GMP regulations, and the smallest contaminant could impact a semiconductor in the high-tech space.
There is an increased relevance in the industry with the new construction/renovation, as more cleanrooms are being renovated to meet updated regulations and energy efficiency measures. Because of the growing and anticipated pipeline of personalised medicine and cell and gene therapy, there is an immediate need for clean space to be built to physically accommodate commercialisation and growth within this area.
Construction of viral vector manufacturing facilities is specialised work that a generalist will be unprepared to handle
It is also critical for the project team to develop a logistics plan during preconstruction around optimising workflow and protecting the client’s schedule. The earlier a logistics plan can be developed prior to beginning construction job, the better prepared the team will be to phase the work in a way that ensures the safest flow of labor, materials, and equipment to and from the space.
Construction of viral vector manufacturing facilities is specialised work that a generalist will be unprepared to handle. Enlisting a highly qualified construction team with specific viral vector manufacturing experience and success will help ensure your project is built to modern industry standards. They also understand how to anticipate problems unique to this emerging sector, work effectively with project partners, and develop creative solutions that will protect your investment.
Top image: The completed cleanroom