Traditional methods of microbial detection tend to be labor-intensive and take more than a day to yield results. Rapid methods for microbial detection can be sensitive, precise, and quick. Yet the pharmaceutical and biopharmaceutical industries have been slow to embrace these techniques. To understand rapid microbial-detection methods better, Pharmaceutical Technology discussed the benefits, application, and challenges they entail with Orla M. Cloak, commercial development manager of rapid testing solutions at Lonza (Basel); Lori Daane, vice-president of Celsis Rapid Detection (Chicago); Maitry Ganatra, program manager at Pall BioPharmaceuticals (Port Washington, NY); Wayne Miller, field marketing manager, and Martha S. Rook, marketing and regulatory manager at Millipore (Billerica, MA); Geert Verdonk, senior research scientist for quality at MSD (Oss, The Netherlands); and John A. Williams, leader of the rapid microbiological methods research and development program at Baxter (Deerfield, IL).

Definition of rapid microbial methods

PharmTech: What are rapid microbial methods?

Miller: "Faster" means in a matter of hours, as opposed to days or weeks in some cases. The various techniques do not share a common principle.

Cloak: In general, rapid methods can be grouped into three distinctive categories in accordance with their application. These categories include qualitative, quantitative, and identification methods. Qualitative rapid methods provide a presence or absence result that indicates microbial contamination in a sample. Quantitative methods provide a numerical result that indicates the total number of microbes present in the sample. Identification methods provide us with a species or genus name for the microbial contaminant in a sample.

Various rapid methods are available and in use in the industrial microbiological market today. They tend to be based on various technology platforms. The more common technologies include nucleic-acid-based detection, which uses DNA or RNA targets; antibody-based detection; biochemical; enzymatic detection such as adenosine triphosphate (ATP) methods; impedance methods; and flow-cytometry-based methods.

Advantages and disadvantages

PharmTech: What are the benefits of RMMs?

Daane: From a manufacturing perspective, a faster time to result enables companies to release raw materials quickly, transfer in-process work to the next stage, and bring finished products to market, which shortens the production cycle, reduces inventory requirements, and frees up working capital. Realizing these benefits requires a rapid method that can match the requirements of the manufacturing line in terms of testing throughput.

Significant savings from rapid methods also come from the ability to identify, contain, and recover from a contamination event quickly. The financial, supply-chain, and brand benefits of being able to recall affected products from distribution centers before they reach customers are obvious.

In addition, some rapid methods help laboratories reduce worker subjectivity. Automated systems that provide test results in a clear, pass–fail approach take the guesswork out of plating and waiting.

Cloak: Rapid methods' advantages include ease of use, high-throughput capabilities, minimal training requirements, compliance with process-analytical-technology (PAT) initiatives, high specificity and sensitivity, ability to interface with laboratory information management systems, and data-trending ability. These characteristics could potentially contribute to better control, quality, and efficiency in the manufacturing and product-release processes.

PharmTech: What are the disadvantages of RMMs?

Miller: One disadvantage is that not one RMM has been able to replace traditional methods in total. I believe that is coming, but it is a slow process.

Ganatra: The rapid methods require upfront capital investments, and the cost per test is high compared with that of culture tests. Rapid methods are technically more complex than culture methods.