Celsis Accelerates Microbial Testing

Detecting microbial contamination throughout the manufacturing process is an important consideration for pharmaceutical companies. Adenosine triphosphate (ATP) bioluminescence is one methodology that detects contamination faster and is the specific technology focus of Celsis International PLC (Chicago, IL, www.celsis.com). The company uses ATP bioluminescence as the basis of its microbial detection system to reduce delays associated with microbial testing.

"Over the past few years, pharmaceutical and biopharmaceutical companies have been embracing lean manufacturing to increase quality and reduce cost and production time," says Judy Madden, vice-president of strategic development at Celsis. "Rapid microbial detection is a lean solution. Rapid systems address many wastes inherent within the lean principles, including overproduction, waiting, inventory, processing, and defects."

Celsis supplies rapid testing systems (reagents, instrumentation, and related software) to detect and measure microbial contamination in raw materials, in-process materials, and finished goods. Its system uses bioluminescence to detect ATP released from the cells of microorganisms that may be present in a sample. Standard ATP bioluminescence uses the enzyme luciferase and the substrate luciferin to catalyze the conversion of microbial ATP to emitted light. The amount of light emitted from this reaction is directly proportional to the amount of ATP present.

Enhanced ATP bioluminescence

Celsis uses standard ATP bioluminescence as the basis of its "RapiScreen" Health system. To enhance the bioluminescence assay, the company uses adenosine diphosphate (ADP) and microbial adenylate kinase (AK) to amplify ATP in its "AKuScreen" reagent platform, an approach it says offers advantages over standard ATP bioluminescence.

"Given the ability of enzymes to affect reactions without being depleted, it is possible to use microbial AK to generate an almost unlimited amount of its products," says Lori Daane, technical director of Celsis. "Since ATP is one of those products, the longer the AK reaction is allowed to proceed, the more ATP is generated, and the greater the bioluminescence signal. In one minute, the AK enzyme can be used to produce approximately 40 times more ATP than the organism originally contained."

The advantage of ATP bioluminescence over other microbiological testing methods is to reduce the time to generate the results: from three to five days with traditional microbiological testing methods to 24–48 hours with ATP bioluminescence, says Daane. Using AK in ATP bioluminescence to enhance the bioluminescence assay further reduces the time to result to 18–24 hours, she adds. Bacteria can be detected in as few as 18 hours and mold in 24 hours. In contrast, it generally takes from three to five days to culture microorganisms on specific agar-based media to levels that may be detected as colony-forming units visible to the naked eye, explains Madden.

The accelerated time to result allows for early release of finished product and a reduction in manufacturing lead times. "The earlier confirmation of product quality starts a cascade of benefits, including a reduction of quarantined inventory, which reduces invested working capital, and shorter manufacturing lead times that drive reductions in safety stock, generating further reductions in working capital requirements," says Madden.

"And when contamination events do occur, the accelerated time to result allows for earlier detection, containment, and response," she adds. "Corrective action aimed at identifying the root cause of the problem typically improves the sooner it can be initiated. Finally, the release of replacement product to distribution also benefits from reduced microbial quarantine delays."

The US Food and Drug Administration (Rockville, MD, www.fda.gov) accepted a Celsis drug master file (DMF) for its rapid detection method systems. The Celsis DMF shares specific regulatory information with the FDA, including details about reagent composition, claim support data, and manufacturing details. The DMF allows FDA to evaluate pharmaceutical applications in conjunction with the Celsis DMF when referenced by a pharmaceutical company.

Company's origins in enzyme technology

Celsis was founded in 1992 in Cambridge, England following completion of research in enzyme technology. It was floated on the London Stock Exchange in 1993 to become Celsis International PLC. In 1994, a small team, including current Celsis CEO Jay LeCoque, was recruited from Baxter International (Deerfield, IL, www.baxter.com) to start commercializing the business in the United States.

Two subsequent acquisitions—Leberoc Testing, Inc., in 1996 and Scientific Associates, Inc., in 1997—served as the basis for Celsis's analytical services division, which today provides outsourced analytical services.

This year Celsis acquired In Vitro Technologies, (IVT) Inc., expanding its portfolio in drug discovery and development to provide services and products to the in vitro ADME (absorption, distribution, metabolism, and excretion) toxicology market. IVT's products and services are used in the screening of drug compounds early in the discovery process.