Sample preparation is the cornerstone of any biocompatibility assessment.  If the sample is not prepared correctly the rest of the study conduct is effectively mis-dosed.  In the pharmaceutical world this is a terrible error in study conduct and equally in the medical device arena it needs to be understood.  Many people will ask what has changed in ISO 10993-10 since 2002 and focus solely on that.  This is a terrible lack of understanding.  It is irrelevant how many animals were used if they were not dosed with a proper extract.  Any evaluation of enduring compliance should first and foremost evaluate the method of the extraction process.  As time has marched on the expectations for proper extraction conduct as tightened immensely.   ISO 10993-10 has updated once since 2002 where as ISO 10993-12 has updated twice.  Extract ratios used previously have been removed.  The expectation for surface area calculations over weight to volume ratios has become almost non-negotiable.