Why Vivarium Design is Crucial for Xenotransplantation Research and Product Development

April 20, 2023

Each year fewer than half of the people on an organ transplant waiting list receive donor organs. This results in approximately 15 people dying each day. Experts agree that even if all potential human donors elected to donate, the availability of human organs would be less than the projected future need for transplants.

This imbalance is currently driving fast-paced research into xenotransplantation or the implantation of live cells, tissues, or organs from a nonhuman animal source into a human recipient.

GBA was approached by a xenotransplantation research client to assist in assessing and renovating an existing building that was decommissioned 15 years prior to be used for research and product development.

The purpose of this article is to outline the systematic and comprehensive approach necessary to investigate, evaluate, design, renovate and validate the existing barrier facility where ultra-sensitive immuno-compromised swine would be housed and utilized to advance potential life-saving research and product development.

For Building Xenotransplantation Research Facilities, Speed and Compliance are Crucial

The driving force behind GBA winning this project was the speed to market. The client was attempting to create a viable form of liver tissue xenotransplantation utilizing gene-modified swine. This project was under the purview of both the American Association for Laboratory Animal Science (AALAC) and the United States Department of Agriculture (USDA) regulatory bodies. The project included:

Challenging the existing facility systems to determine renovation needs.
Ensuring the integrity of the barrier facility envelope.
Modifications for better animal husbandry/piglet rearing.
Addition of a new surgical suite for animal delivery via c-section within the barrier.
New security system with card access and video security cameras throughout.
Creation of a new neonatal room.
Addition of a new crematory for carcass disposal.
New chillers, controls and heating, ventilation and air conditioning (HVAC) upgrades.
Several dysfunctional components requiring immediate repair or renovation.
Design and construction completed in less than one year, meeting the client’s deadline.

To Meet Requirements for This Project, a Vivarium Barrier Facility Design was Chosen

Due to the specific needs of the client, a vivarium barrier facility design was critical for this project. A barrier facility is a subset of a vivarium. A vivarium is a building designed and operated for keeping animals under seminatural conditions for observation, typically for laboratory research. A barrier facility is a specialized version of a vivarium where the design and operation create a microbiologically impervious perimeter enclosing a room or group of rooms for housing animals.

A vivarium contains a room pressurization scheme and layout to keep microbes contained within the building, while a barrier facility utilizes a room pressurization scheme and layout to keep microbes out of key animal holding rooms. This made the design a perfect fit for the client’s xenotransplantation research needs.

For Speed and Cost Saving Reasons, Renovation Was Selected

Due to time constraints, the best life science construction option for the client was renovation. The building being considered by GBA’s client had gone through several renovations with the most recent in 1999, where it was renovated into a barrier facility for swine and only utilized for a few years. The building was purchased by a local medical center and was decommissioned but minimally maintained to keep the building in a potentially operable condition. Fast forward to 2018, GBA’s client began negotiations with the medical center to acquire the building after having been in disuse for more than 15 years.

Schedule:

February 1, 2019 – Turnkey proposal submitted
February 15, 2019 – Project started
March 18, 2019 – Issued for permit was submitted to Authority Having Jurisdiction (AHJ)
October 20, 2019 – Substantial completion

GBA assembled a full-service team consisting of design architects and engineers, building system experts, a commissioning team and a construction management team to take this project from feasibility through completion which ultimately resulted in a turn-key project that was handed over to the client.

Project Phases

Feasibility/Turnkey Pricing

The client was in negotiations with the building owner to purchase the building. The building owner had provided a list of items needing repair or replacement along with a cost to credit against the sales price. The team performed a site visit for an initial visual inspection. After the inspection, the team met with the client and put together calculations to move the conversation forward into negotiations with the building owner. They provided an up-front high-level Rough Order of Magnitude (ROM) construction cost of the building including the credits to position a better negotiation with the building owner.

The original drawings were reviewed and ViroCon, a GBA affiliate, performed an in-depth HVAC and Building Automation System (BAS) analysis to confirm operational readiness proving the temperature and pressurization controllability was functional. The team updated the high-level ROM construction costs incorporating the on-site findings. From there a turn-key price for maintenance, upgrades, commissioning and start-up was provided. The team also provided up-front system performance analysis on the HVAC, airflow rates, chiller capacity and boiler capacity.

Programming

The team reached out to the original contractors that installed the renovations in 2000 and were able to locate the original HVAC Testing, Adjusting and Balancing (TAB) report. From there, programming was developed incorporating the new requirements for the building systems.

Rooms were added, re-purposed or deleted with additional finish upgrades to vivarium and non-vivarium areas within the building. Temperature, pressure and humidity controls were modified, and the HVAC was upgraded to include a higher degree of filtration.

Additional testing, inspection and cleaning were performed on the ducts and tanks.

Construction Documents

GBA provided modifications to the design while working alongside the construction trade sub-contractors to minimize the cost to implement changes along the way. Reviewing these changes minimized unintended consequences. Equipment was routed and tied-in correctly the first time based on client-specific operational needs.

Renovation Construction

Constant communication between trade sub-contractors, construction management (CM) and designers was critical to the success of this project. There were many challenges along the way due to the nature of this project and unexpected issues needing repairs and upgrades that were discovered.

The full team worked closely during the renovation to develop, review and answer appropriate requests for information (RFI) and submittals to keep the project schedule on track.

By performing a design for renovation by working with construction trade sub-contractors, the cost was minimized to implement changes.

Commissioning / Start-Up

Design, CM, the Commissioning Agent and trade sub-contractors worked closely to fully test and start-up/commission approximately 15 different systems. To assist with this effort, both the Design and Commissioning Agent teams developed detailed step-by-step procedures including required system parameter measurements. These detailed procedures and in-depth testing resulted in additional system components requiring repair or replacement. The result was a quick and efficient start-up of all systems.

Results

GBA developed a unique, full-team approach to drive a solution for the client in a limited amount of time. A key component for success was a Vivarium barrier facility design. Using this approach addressed how to efficiently and economically design, inspect, test, renovate and start-up the building in less than 10 months incorporating all the systems that had thousands of components over 15 years old.”