Once again we got a great turnout to our survey, thank you to everyone who responded! Secondly, it’s apparent that the industry is inconsistent in regards to cytotoxicity testing being performed. First we’ll present the data and then dive a little deeper into the results in terms of the reasons why and the impact of the results. At a high level, 57% of respondents stated that they used the MEM Elution (qualitative) assay whereas the remaining 43% used either the MTT or NRU (quantitative) assays. There was a good representation of consultants, manufacturers and biocompatibility labs who replied from around the world. Lastly, 57% of respondents said they’ve seen cytotoxicity methods non-uniformly accepted around the world while 43% said that it is. Of those respondents who reported non-uniform method acceptance, 63% had performed the MEM and 37% had used a quantitative method.
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When the initial migration to quantitative methods began, the biggest feedback that we heard was that some of the methods were much harder to pass than the legacy MEM elution method. As many people know, failing any test can lead to a litany of justifications and investigations to be performed ranging from simply performing a series of extract dilutions all the way to executing a long and expensive wound healing study in pigs. While the requirement for a pig study is not common, it does happen. If you have a product going into breached skin and fail cytotox, FDA or other notified bodies may want to know for sure if the cytotoxicity will affect a normal healing response. In the MEM, the scorer looks at the plate of cells under a microscope and gives an educated estimation at the level of cell viability whereas in the quantitative methods, a calibrated instrument is giving the result. For the quantitative methods, if passing is 70% and you get a 69%, you still fail even if it’s only by 1%. It’s high grammar school all over again. In regards to uniform method acceptance, there was no trending in one method type being accepted more than others internationally. It’s likely that different methods may be acceptable based on the context of individual device types or if a certainly regulatory agency or reviewer may have varying opinions which is certainly the case in other submission items.
There is always a balance between practicality and guideline interpretation and that is most likely where the mix in methods is coming from. There are only a handful of major biocompatibility labs around the world who can push the agenda of a certain method and they can influence a test method to use or a biological evaluation plan perhaps more so than any other entity besides an actual ISO 10993 document. If you’ve ever heard about ISO 10993 TC 194 meetings though, they often start with a big agenda but rarely complete it due to differing opinions. The pathway to harmonized guidelines isn’t short.
Thank you again to everyone who responded, stay tuned for our next survey!
There is always a balance between practicality and guideline interpretation and that is most likely where the mix in methods is coming from. There are only a handful of major biocompatibility labs around the world who can push the agenda of a certain method and they can influence a test method to use or a biological evaluation plan perhaps more so than any other entity besides an actual ISO 10993 document. If you’ve ever heard about ISO 10993 TC 194 meetings though, they often start with a big agenda but rarely complete it due to differing opinions. The pathway to harmonized guidelines isn’t short.
Thank you again to everyone who responded, stay tuned for our next survey!
