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Millipore Launches TMA-Based Mycoplasma-Detection Test for Biomanufacturing

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By Ben Butkus

Millipore this week launched a nucleic acid amplification-based test developed in collaboration with recent Gen-Probe offshoot Roka Bioscience for detecting Mycoplasma contamination in biopharmaceutical manufacturing.

The test is a product of an ongoing collaboration begun in 2005 between Millipore and Gen-Probe to develop faster and more sensitive tests for pharmaceutical and biotech manufacturing. In September, Gen-Probe spun Roka out from its industrial testing business, and transferred its agreement with Millipore and pertinent technology licenses to the new company.

The new test, called the MillProbe detection system, combines Millipore's sample-preparation technology with transcription-mediated amplification, or TMA, methods developed by Roka, to detect Mycoplasma contamination in hours as opposed to a month or more for traditional cell-culture methods.

"From a customer perspective, Mycoplasma is really of great value for them to detect rapidly," Martha Rook, Millipore's Mycoplasma assay marketing manager, told PCR Insider this week. "It can be a big problem in biopharmaceutical manufacturing, and right now, because the growth-based test that is currently used takes so long, there is really no effective in-process screen for Mycoplasma."

There is at least one other nucleic acid-based Mycoplasma detection kit on the market: the PrepSEQ extraction and MicroSEQ detection assays manufactured by Life Technologies business unit Applied Biosystems and offered by Agawam, Mass.-based testing company Microtest Laboratories.

Microtest last week updated and reissued a white paper that it had originally released last year outlining the benefits of advanced Mycoplasma testing such as Applied Biosystems' real-time PCR-based test.

Microtest had been offering conventional culture-based Mycoplasma testing for several years, but began working with Applied Biosystems last year to validate the PrepSEQ and MicroSEQ methods, Daniel Schumacher, manager of virology and biologics for Microtest, told PCR Insider this week.

Like the Millipore test, the PCR-based test offered by Microtest promises to provide a turnaround of hours as opposed to the typical month or more for cell culture; has increased sensitivity and specificity; and works whether the organism is alive or dead.

Schumacher said that the Applied Biosystems test can detect some 90 species of Mycoplasma, and thus may have greater specificity than Millipore's test, which can detect about a dozen different species, according to the Millipore's website. Otherwise, the two tests are comparable, he added.

But Millipore claims that its TMA-based test provides a few advantages over PCR-based Mycoplasma testing. Namely, because TMA directly targets the organism's ribosomal RNA, there is "more target" available to work with than in PCR, which increases sensitivity, Rook said.

"People in the pharmaceutical industry are generally more familiar with PCR; whereas I think people would be more familiar with TMA in the clinical diagnostics and blood screening markets," Rook said.

A second advantage, according to Rook, is that MilliProbe is the first test to incorporate Gen-Probe's new background reduction technology, which protects the assay from contamination that can lead to false positives.

"I think one of the common concerns people have with molecular methods, particularly PCR, is the possibility of false positives, because it's an amplified reaction," Rook said. "You could have DNA present in the environment that could get into your assay and cause false positives."

The background reduction technology modifies target RNA during a closed, protected sample-preparation step, and only the modified RNA is amplified. Besides protecting against false positives, this technology doesn't require stringent workflow controls and is easier for lab technicians to implement than in PCR methods, Rook said.

Regardless of their differences, both tests promise to save time and money for biopharmaceutical manufacturers. Mycoplasma contamination of a facility can force manufacturers to destroy entire drug batches and shut down production facilities for extended periods, Millipore said.

According to Microtest, the biggest current market for Mycoplasma testing may be European biomanufacturers, as the real-time PCR method has been fully accepted for mycoplasmal screening at any stage by the regulating authorities of the European Pharmacopoeia.

Not so in the US, where the Food and Drug Administration has not ruled on real-time PCR or other nucleic acid-based tests for screening Mycoplasma, and manufacturers must still eventually perform direct cultivation and cell culture to demonstrate a lack of contaminant.

Still, Schumacher said, a rapid and sensitive Mycoplasma test can provide peace of mind to biomanufacturers that they can safely continue operations while waiting for the results of conventional testing, which could take anywhere from 28 to 35 days.

In addition, the FDA may eventually consider approving nucleic acid-based detection methods for product release screening at a future time, although Schumacher said he is not aware of any plans by the agency to do so.

Research tool providers are certainly trending in this direction however, Rook said.

"Mycoplasma has been a problem for quite some time, but there haven’t been good, rapid testing solutions," she said. "Now we're beginning to see that molecular assays are beginning to be more accepted, and we're seeing an interest from regulatory agencies to have rapid testing available for pharmaceutical companies."

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