Genetic Engineering & Biotechnology News

NOV15 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Genetic Engineering & Biotechnology News | | NOVEMBER 15, 2017 | 11 with an assay that will be used as the prod- uct continues development. Dr. Bortolotto advises, "Although a binding ELISA is faster to develop for early phases, often one subse- quently moves to CBAs for later phases. This becomes a bigger challenge. Thus, it's impor- tant to start as soon as possible to create a well-defined potency assay that will carry the product into the future." Call the Statistician While carpenters rely on tools such as tape measures and T-squares, statisticians often employ the 4-Parameter Logistical (4PL) function to make sense of bioassays, notes Martin Kane, managing data scientist, statistical and data sciences practice, Expo- nent. "Potency assays measure two versions of a product against each other. This type of statistical calculation is not particularly new, but there are caveats to using the 4PL. Choosing the best one, along with employ- ing additional statistical tests, is critical." Kane uses the Rodbard version of the 4PL. He explains, "The 4PL consists of four parameters: a sigmoidal curve, upper asymp- tote, lower asymptote, slope (at midpoint of sigmoidal curve), and the EC50 (half maxi- mal effective concentration). With these values for two samples, one can derive the relative potency of a product." It seems simple on the surface to obtain the numbers and then just plug-and-play, but that's not the case. "Sometimes, comparing the historical 4PL calculation with those [which are] newly derived can be tricky," Kane reports. "If, for example, three of the four measures compare equivalently between test and control, some- times scientists try to force the fit of one or more parameters. This may be wholly inac- curate. It's usually significantly more complex than that. The best thing to do is to include a professional statistician who can use more sophisticated means to verify that you are de- termining potency accurately." Perceval Sondag, Ph.D., senior man- ager of statistics, PharmaLex, agrees. "It is important to involve statisticians immedi- ately as the product begins development," he comments. "A strong collaboration in which scientist and statistician work together al- lows both to share their unique perspectives. Both should be teaching each other." According to Dr. Sondag, a statistician can help scientists to better understand the USP's requirements and also create simulations ex- ploring realistic scenarios that compare, for example, precise versus imprecise assays and optimal versus suboptimal designs (Figure 2). "One mistake many scientists make is draw- ing conclusions indirectly. For example, one may declare their data prove similarity sim- ply because they fail to demonstrate non- similarity. This is a big mistake. One should instead seek the guidance of a statistician to directly prove the data are similar." Dr. Sondag concludes, "Don't just use software and expect to generate the correct results—ask for help. Involve an expert from the beginning stages so that your assays are designed correctly from square one." Drug Discovery VIAFLO II ASSIST VOYAGER II Adjustable Tip Spacing Pipette Motorized tip spacing enables parallel transfers of multiple samples between labware of different sizes and formats. The tip spacing can be changed by the simple push of a button, no manual adjustments or two handed operations are needed. ARE YOU PIPETTING SAMPLES BETWEEN DIFFERENT LABWARE FORMATS? EVOLVE VIAFLO 96 I 384 Figure 2. A bioassay is commonly a comparison between the biological activity produced by a batch of a test product ("Test"), and the biological activity produced with batch of a reference product ("Reference"). This comparison usually depends on a single measure, the relative potency, which is usually derived from a four-parameter logistic curve. Computing this curve requires the use of statistical approaches to test the parallelism between two curves. Some approaches, such as those developed by PharmaLex, rely on equivalence tests. PharmaLex aims to derive equivalence margins to test parallelism in bioassays, without the need for historical data or expensive additional experience.

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