99% Prevention, 1% Detection
Contamination is almost never immediately detectable. Too often, it becomes apparent only after processors have expended considerable time on a batch. If you have one bacterium in a reactor, dividing every twenty minutes, versus cells that divide every 24 hours, which would you bet on? asks Cox.
In biotech, contamination control is 99% prevention, 1% detection. That percentage point is critical though, since companies rely on it to demonstrate that processes are clean. Because of the time lag between when a swab is taken and the resulting culture turns positive, contaminated product will not likely be picked up until late in manufacturing and sometimes only after release, notes Stacy Montgomery, Ph.D., director of global marketing for Biolog (www.biolog.com).
Biolog produces microtiter well-based microbiology tests that identify more than 2,000 unique organisms based on their carbon utilization. Panels consist of 95 wells containing various sugars and amino acids, plus one control well. Biolog offers panels for major organism typesGram positive, Gram negative, yeast, and filamentous fungi. As they use carbon sources for food, microorganisms generate NADH, a biological reducing agent, which transforms a tetrazolium redox dye from neutral color to purple.
Plates may be read manually, on a microplate reader, or through a completely automated system. Each assay uses two time points within one of two time regimes: 4 hours for fast-growing organisms like E. coli, and 16 hours for slow-growing Gram negative non-enteric bacteria. Organisms show unique fingerprints for carbon utilization based on their preferences for some carbon sources over others. Microorganisms are identified by comparing their utilization patterns against those stored in a database.
The fully automated OmniLogID contains an incubator, analyzer, computer, printer, software for reading Biolog’s MicroPlates, a turbidimeter for preparing inocula, colony-magnifying lamp, and an eight-channel electronic pipetter. Biolog also offers an semi-automated MicroLog analyzer and the MicroLog series manual systems.
BioVigilant Systems (www.biovigilant.com) distinguishes between standard microbiologic detection systems that are merely rapid and those that are instantaneous. Rapid systems can never be continuous since they employ inherently slow, labor-intensive chemical and biological methods. BioVigilant’s Instantaneous Microbial Detection (IMD) systems use optics to verify the presence (or absence) of microbes without growing cells or chemical staining.
BioVigilant offers two types of instruments for pharmaceutical-quality applications: IPD (Instantaneous Particle Detector) and IMD. Both may be used as part of a process analytical technology (PAT) program for microbial alerts or continuous monitoring/trending of air and process liquids.
IMD requires almost no sample preparation or human intervention. Since it operates nondestructively, IMD provides a high level of assurance during downstream processing of concentrated product streams, especially during fill/finish operations, according to the company. Its only limitations are the inability to detect viruses or identify microbes by species.