title: Designing a tool allowing for a standardized assessment of resistance to drug diversion.
abstract: OBJECTIVE
  Drug diversion is a growing problem in numerous countries. Some laboratories have developed tamper-resistant formulations. The problem for healthcare authorities is now to assess new formulations developed to limit the risk of diversion for administration by another mode and intended mode. It would be helpful to have a pertinent panel of in vitro tests allowing assessment of how a formulation may be altered, both for healthcare authorities and for laboratories, so as to implement adequate sanitary measures. We designed a methodology/tool allowing assessment, in a standardized manner, of the formulation's resistance to drug diversion. We present the various steps leading to the construction of the scale and to its first use.
  
  
  METHODS
  Creating a Steering Committee - Choosing assays or parameters - standardized by a monograph of the European Pharmacopoeia and pragmatic assays related to users' behaviors - for the assessment of formulation resistance to drug diversion. Designing a scale: i) applying all these tests to a panel of formulations; ii) applying a score by drug and by test; and iii) attribution of weighting per test and calculating the total score for a drug.
  
  
  RESULTS
  Eight tests or parameters and 14 drugs (diverted drugs and controls) were chosen. Buprenorphine Subutex® had the lowest score and flunitrazepam Rohypnol® the highest.
  
  
  CONCLUSIONS
  Our tool allowed classification of the various drugs selected. This classification correlated with results of postmarketing authorization assessment. Rohypnol®, which was the object of many measures, including formulation changes, obtained the highest score in our study.
authors.affiliation: Nantes University Hospital, Institut de Biologie, Centre d'Evaluation et d'Information sur la Pharmacodépendance, Clinical Pharmacology Department, Service de Pharmacologie Clinique , 9 quai Moncousu, 44093 Nantes cedex 1 , France +33 240084096 ; +33 240084097 ; caroline.vigneau@chu-nantes.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Victorri-Vigneau
authors.forename: Cedric
authors.initials: C
authors.lastname: Collin
authors.forename: Catherine
authors.initials: C
authors.lastname: Messina-Gourlot
authors.forename: Christel
authors.initials: C
authors.lastname: Raffournier
authors.forename: Michel
authors.initials: M
authors.lastname: Mallaret
authors.forename: Jérôme
authors.initials: J
authors.lastname: Besse
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Courne
authors.forename: Nathalie
authors.initials: N
authors.lastname: Richard
authors.forename: Véronique
authors.initials: V
authors.lastname: Sébille
authors.forename: Philippe
authors.initials: P
authors.lastname: Arnaud
mesh_terms: D000662:Amphetamines; D000701:Analgesics, Opioid; D001569:Benzodiazepines; D002626:Chemistry, Pharmaceutical; D004349:Drug Packaging / Q000379:methods*; D004335:Drug and Narcotic Control; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D063487:Prescription Drug Misuse / Q000517:prevention & control*; D017751:Safety Management
chemical_list: D000662:Amphetamines; D000701:Analgesics, Opioid; D004364:Pharmaceutical Preparations; D001569:Benzodiazepines
keywords: abuse; assessment tool; diversion; drug formulation; tampering