Locus Biosciences is one of three Honorable Mention Award winners this year. The other two are Biocon Biologics and the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at Children’s Hospital of Philadelphia.
The design attributes and operational procedures Locus Biosciences incorporated into their new facility go beyond the Regulatory requirements. ISPE would like to recognize Locus Biosciences for building a facility that will produce safe and effective products.
Fighting Back Against Bacteria
Founded in 2015, Locus Biosciences is a clinical stage biotechnology start-up that develops Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas3-enhananced bacteriophage (crPhage™) precision antibacterial products to address critical unmet needs in bacterial infections and microbiome indications in oncology, immunology, and central nervous system therapeutic areas. Based in Morrisville, North Carolina, the company has become a world-leading developer of products based on today’s most advanced CRISPR technology. As demand for their product has grown so did the need for more space.
“Our product is a bacteriophage that is very effective at attacking E. coli,” said Joseph Nixon, Senior Vice President. “Unfortunately, many contract manufacturers use E. coli cells to manufacture other products. Therefore, producing the bacteriophage in those facilities was impossible.”
Faced with extremely limited options, Locus leadership decided they needed build their own dedicated space to ensure their research and clinical trials would be able to advance unimpeded.
Locus’ entire process is a comprehensive raw material to finished dosage form, produced in one facility. In the new space, bacteriophage are produced in an aqueous buffered solution. The process steps include:
Upstream processing of high concentrations of potentially virulent and non-virulent bacteria, including introduction of bacteriophage into bioreactors for amplification of phage
Downstream processing including clarification filtration, tangential flow filtration (TFF), chromatography, and bioburden reduction filtration
Sterile filtration and vial/syringe filling
The process requires a high-quality clean space environment that minimizes contamination and provides a safe and secure barrier for potentially virulent and non-virulent bacteria and bacteriophage.
Locus was able to renovate a 30-year-old, one story shell space into a leading-edge BSL-2 laboratory and cGMP biomanufacturing space. The new facility provides for revolutionary advancements in biocontainment through its leading-edge design and efficiencies. Several innovative facility advancements include:
The first commercial BSL-2 multi-bacteriophage facility in the U.S. that can work with 5-litre and up to 200-litre bioreactor capacity
Process areas designed to provide unidirectional traffic flow
HVAC system with higher-than-average air change rates
Aseptic filling using a VanRx Microcell, a closed gloveless isolator
All liquid waste is collected through the SUSs and disposed via the Actini sterilization system
The space includes three equally capable suites with the ability to provide for the simultaneous and interchangeable production space. Each of the three suites is fully interchangeable with the capacity to execute any part of the process.
Due to the ubiquitous nature of the product (i.e., the ability for bacteriophage to get anywhere), containment and safety were essential when designing the new facility. In addition to the required HEPA filtration in and out of each suite, Locus provided the additional safeguard of an independent bubble for each suite through secondary airlocks. The additional airlocks and resulting innovative pressure cascade resulted in two levels of bacterial containment.
To further enhance facility safety, the HVAC system is designed with a purge system function. In the event of an emergency, the system is designed to transition to 100% fresh air in with 100% exhaust. The facility’s process area was designed to provide unidirectional traffic flow for both personnel and materials, four separate airlocks were constructed for each of the three separate suites and each suite was designed with a Personnel Airlock (PAL) and Material Airlock (MAL) for both entry and exit.
Locus’ dedication to safety was stellar throughout construction as well. Through extensive planning and skilled execution, the project was completed with 67,070 work hours, no COVID-19 cases or impacts on any workers (despite ongoing construction during the pandemic), and 0 recordables or lost time.
Nominate Your Facility for the 2022 FOYA Program!
Apply for a chance to join this prestigious list of innovative game-changers and let ISPE honor your organization as a 2022 FOYA program winner. Applications must be submitted by 19 November 2021.
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