title: Consistency in the safety labeling of bioequivalent medications.
abstract: OBJECTIVE
  Bioequivalent medications are required by the Food and Drug Administration to have identical warnings on their labels. This requirement has both clinical and legal importance, yet has never been validated. We sought to determine the real-world consistency of electronic labeling for bioequivalent drugs from different manufacturers.
  
  
  METHODS
  Using natural language processing, we indexed the adverse drug reactions (ADRs) found in the Adverse Reactions and Post-Marketing sections of 9105 structured product labels. We calculated the standard deviation in ADR labeling for each bioequivalent drug and the percent deviation of each generic label from its corresponding brand. We also analyzed the performance of individual generic manufacturers. For the 25 drugs with the greatest discrepancy in labeled ADRs, we performed manual review to identify causes of inconsistency.
  
  
  RESULTS
  68% of multi-manufacturer drugs had discrepancies in ADR labeling. For a given drug, the mean deviation in number of labeled ADRs was 4.4, and the median was 0.8 (IQR 0 to 3.2). The mean range in number of labeled ADRs was 12 +/- 0.9, and the median was 2 (IQR 0 to 9). Overall, 77.9% of generic manufacturers produced labels differing from brand. Causes of inconsistency included missing tables, outdated post-marketing reports, and formatting issues.
  
  
  CONCLUSIONS
  Despite FDA mandate, bioequivalent drugs often differ in their safety labeling. Physicians should be aware of such differences and regulators should consider new strategies for harmonizing bioequivalent labels.
authors.affiliation: Regenstrief Institute, Indianapolis, IN 46202, USA. jduke@regenstrief.org
authors.forename: Jon
authors.initials: J
authors.lastname: Duke
authors.forename: Jeff
authors.initials: J
authors.lastname: Friedlin
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000331:legislation & jurisprudence / Q000592:standards*; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000592:standards*; D004348:Drug Labeling / Q000331:legislation & jurisprudence / Q000592:standards*; D004335:Drug and Narcotic Control / Q000331:legislation & jurisprudence; D016568:Drugs, Generic / Q000009:adverse effects*; D019983:Guideline Adherence; D017408:Guidelines as Topic; D006801:Humans; D009323:Natural Language Processing; D061214:Patient Safety; D017891:Pharmacoepidemiology; D018570:Risk Assessment; D012307:Risk Factors; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence / Q000592:standards*
chemical_list: D016568:Drugs, Generic