On August 22, 2008, the FDA published a final rule amending its regulations regarding changes to an approved new drug application, biologics license application, or medical device premarket approval application.  Specifically, the rule provides that a labeling change to an approved product to reflect "newly-acquired information" that adds or strengthens a contraindication, warning, precaution, or adverse reaction, may be made prior to FDA approval upon the submission of a "Changes Being Effected" or "CBE" supplemental only if there is sufficient (reasonable) evidence of a causal association with the use of the drug, biologic, or device.  In a change from the January 16, 2008 proposed rule, CMS is revising the definition of “newly acquired information” to clarify that data, whether derived from reports of adverse events or from new clinical studies or new analyses of previously submitted data (e.g., meta-analyses) needs to be of a “different type or greater severity or frequency than previously included in submissions to FDA.”  This standard could limit the circumstances under which a company can make changes without prior FDA approval.  The rule is viewed by many as FDA’s attempt to address preemption questions raised in state product liability lawsuits against holders of marketing applications for their failure to amend labeling before or without FDA’s approval.  The rule is effective September 22, 2008.