Genetic Engineering & Biotechnology News

NOV15 2017

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8 | NOVEMBER 15, 2017 | GENengnews.com | Genetic Engineering & Biotechnology News Avoiding Costly Errors in Bioassay Development See Assay Development Errors on page 10 and quality control, and establishing critical collaborations with expert statisticians and IT personnel. Avoiding Costly Mistakes Early in the process of assay develop- ment, scientists often must rely on limited product production experience, meager clin- ical experience, and incomplete knowledge about assay capabilities. "Despite those drawbacks, optimizing bioassays for biolog- ics still requires setting realistic project spec- ifications," advises David Lansky, Ph.D., president, Precision Bioassay. He continues, "Scientists often make the biggest mistakes in initial assay design. Ex- amples include always using an assay tem- plate with replicates (or more often pseu- do-replicates) of each sample and dilution combination in adjacent locations. Another issue is having sample groups and dilutions arranged in ways that are likely to be con- founded with location or sequence effects. These designs do not protect estimates of nonsimilarity or potency against bias due to location or sequence effects." But there is a solution, according to Dr. Lansky: "Designs that separate replicates into blocks not only protect against these likely sources of bias, but also support vari- ance components analyses that can inform developers about where to focus effort to improve the assay. While changing templates by hand is challenging—it requires even more focus and attention than usual—random placement of samples can be easily achieved using a pipetting robot. "For perspective: Clinical results submit- ted to the FDA from nonrandomized trials are generally ignored. Why should impor- tant analytical bioassays be held to lower standards?" Another mistake is not paying enough attention to establishing state-of-the-art sta- tistical analysis. "Developing these analyses is a bit harder and less well understood," observes Dr. Lansky. But there are solutions here as well. "The software chosen must include great graphics and highly selective statistics," he continues. "Combining com- prehensive statistical analysis with a well- devised experimental design leads to high precision. Great precision cuts costs and translates to high throughput, which gets the products to market sooner." Precision Bioassay offers their Xymp ® bioassay solution that is designed to com- plement their consulting services. Dr. Lan- sky explains, "We work closely with a sponsor's management and lab teams to help refine assay design including develop- ment, robustness, validation, method trans- fer, etc. In the process, we capture the statis- tical features of the assay SOP in an 'assay protocol.' Data summaries are concisely displayed to enable bench scientists, man- agers, QA, and regulatory staff to quickly understand an assay." Dr. Lansky's take-home message is that companies must carefully weigh early decisions about assay development. "Con- sulting with experts can be a big help. Care- ful assay design can go far to protect you and speed your course to market." Shrinking Assays Enhances Efficiency Potency and bioassays tend to be very complex, costly, and time-consuming. Be- cause of this, there is a push to incorporate automation to save time anmoney. "We are always wondering how to do more with less," notes Robyn Beckwith, Ph.D., associate scientist, analytical devel- opment and QC, product technical devel- opment, Genentech. "We have developed a strategy that automates workflows for po- tency assays using a novel low-volume dis- pensing system (LVDS)." Dr. Beckwith and colleagues built a unique system that leverages contactless liq- uid handling technologies, including acoustic ejection and air-pressurized microvalve hard- ware, to dispense nanoliter- and microliter- scale volumes in an automated assay work- flow. She reports, "We miniaturized and automated a potency assay by integrating multiple off-the-shelf liquid handling instru- ments into a larger system controlled by a unified scheduling software." To establish proof-of-concept for the sys- tem, Dr. Beckwith evaluated an automated homogeneous enzymatic potency assay in miniaturized 384-well format versus the assay performed manually in 96-well format. "We demonstrated equivalence of per- formance in both assays across a linear range. Even with the differences in work- flows, we obtained comparable results. This is especially remarkable because in- corporating acoustic ejection technologies allows dispensing volumes as low as 2.5 nanoliters. This provides tremendous ben- efits, especially when moving into the high- throughput arena. Overall, our system can process more samples, is more economical, and performs comparably to manual po- tency assays." The next step will be establishing proof- of-concept for cell-based assays. "Working with cells is more complex, but we believe the system will provide suitable performance. Further, because it is flexible and customizable, we have the potential for multiplex assays," he says. "We are excited to share information about this one-of-a- Drug Discovery Feature Continued from page 1 Figure 1. Scientists at UCB Pharma warn that bioassay analysis can yield meaningless relative potency results if parallelism is not established. One way to establish parallelism is to run dilution assays that compare product to standard. Such assays should generate a quantitative response showing (A) a parallel-line dose or (B) a sigmoidal log- dose. These can then be analyzed by employing standard statistical methods.

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