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May 05-07, 2014 · DoubleTree by Hilton Berkeley Marina · Berkeley, CA
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Attendees at the 2014 Bioassay Conference held in May in Berkley, CA heard about both the newest statistical and technical tools bioassays, such approaches to OOS results, use of Thaw-and-Go cells and the newest survey about what to monitor to maintain a bioassay throughout its life cycle.
The use of thaw and go cells was the most often mentioned topic and was discussed in multiple talks during the conference. Dr. Helene Gazzano-Santoro of Genentech, included it as number one her list of top four impacts in modern day bioassay development. Both Dr. Gazzano-Santaro and Dr. Surowy of Promega shared technical details about developing bansk of bioassay ready cells. Both speakers gave technical details of optimizing the freezing, thawing and pipetting of these cells. Several attendees also added their experiences during the question and answer session, highlighting that in their experience the confluency of the cells just prior to freezing appeared to be a critical aspect. Most agreed that typically just confluent cells, perform best upon thawing and immediate use.
Another critical component of bioassays is the product reference. Dr. Borer from Lily discussed their approach for qualifying reference material. Since the potency assay is almost always a relative potency assay, there are major concerns that assigning the value of a new reference off the old reference may, over time, lead to an over-estimation of the existing potency or carry through a biased result. To decrease the possibility of either of these occurrences, most firms have now switched to using a primary reference rather than the current working reference to determine potency of a proposed new reference lot. Dr. Seaver, of Seaver Associates, discussed that additional characterization studies and the care which must be taken during the qualification process. Dr. Borer also shared how to calculate the number of assays are required to assign a potency value to a reference lot. This involved knowing the overall precision of the method and understanding the acceptable confidence interval for a reference material.
The topic of out-of-specification results was discussed in a session which included how-to-talks about both removing a single aberrant replicate from the dose-response and what to do in a commercial QC environment when a properly run assay yields an OOS result. Dr. Stan Deming, of Statistical Designs, kicked off the session with a mini-tutorial outlining standard statistical approaches to identifying and defining outliers. Dr. Lansky, of Precision Bioassays, then shared with audiences how the use of model approaches to identifying outliers rather than the simple use of replicate data at a single dose concentration is much more sensitive detector for outliers. Dr. Robinson, of Seattle Genetics finished the session by sharing their red/yellow/green zone approach for retesting potential OOS results. This is a stepwise implementation of stepwise, sequential testing for potency results which are in a zone too close to a specification. The hallmark of this system is that it treats in and out-of-specification results which fall in the yellow zone in an identical fashion
Another hot topic was the use of potency assays to demonstrate product stability. It is currently standard industry practice to include the potency assay as part of the product stability program both during development and to support the commercial products. Two case studies probed the impact of aggregates on potency assays, in one case the aggregates caused an increase in potency and in another it decreased potency. This highlighted how critical it is to perform various stressed studies to determine the impact of aggregates on a specific product/assay combinations. One speaker shared his experience about how small changes in the format of the assay could essentially make the assay "blind" to aggregates. This led to a lively discussion about the use of the potency assay and the overall quality control strategy. Ultimately it appeared there was a consensus, that depending on the availability of other methods to identify aggregates, the sensitivity of the method to low levels of aggregates and existence of other potency assays, a sponsor may elect to use the aggregate sensitive or insensitive format of the assay for final product release.
The conference ended with a presentation about what and how to implement various acceptance criteria. The basis for the talk was draft white paper (Robinson, J et. al.) written by the non-profit organization Biopharmaceutical Emerging Best Practices Association (BEBPA)and published recently by BioProcess International. The paper distinguishes between multiple levels of acceptance criteria which include assay, plate and test sample criteria. This lead to discussion about the use of QC samples and whether they are needed on each plate within an assay run or simply within every assay run (one plate if four plates are launched simultaneously) or if there are specific examples when a QC sample can be eliminated. All agreed that this last case is rare and should be approached with caution. The paper has highlighted the need to include acceptance criteria as part of the overall assay development process. Many attendees were interested in how these criteria should be used to support OOS strategies and the statistical tools needed to monitor these criteria. Clearly new topics for next year's conference!
"The Conference has been quite focused on case studies, sharing not only the speakers experiences and fundamentals but the other participants questions and doubts. Such a nice and useful scientific meeting!!" - Socorro Duran Tellez, Quality Control Manager, Problemed SA de CV
"It is the first time I attend to an IBC Conference and I love it, it was very useful, funny, and illustrative and I return to my mg company with a lot of work to do and wonderful ideas and advices. I took from all the components. Thanks you very much. Congratulations for this great effort and work. I would be glad to attend next year." - Nancy Ramirez Ibanez, Analytical Chemist, Problemed SA de CV
"Very informative. A variety of topics were addressed and open discussion encouraged. It was useful at many levels: from things that need to be considered when developing a bioassay, the impact of product characteristic on any performance to how to manage bioassays during stability studies." - Manuela Grassi, Group Leader, PPD Inc
"Thought provoking and fun." - Marina Feschenko, Scientist II, Biogen Idec Inc
"Educational, and regulatory input for critical potency bioassays." - Lee hwa Lo, Assocaite Director, EirGenix Inc