title: Risk analysis by FMEA as an element of analytical validation.
abstract: We subjected a Near-Infrared (NIR) analytical procedure used for screening drugs on authenticity to a Failure Mode and Effects Analysis (FMEA), including technical risks as well as risks related to human failure. An FMEA team broke down the NIR analytical method into process steps and identified possible failure modes for each step. Each failure mode was ranked on estimated frequency of occurrence (O), probability that the failure would remain undetected later in the process (D) and severity (S), each on a scale of 1-10. Human errors turned out to be the most common cause of failure modes. Failure risks were calculated by Risk Priority Numbers (RPNs)=O x D x S. Failure modes with the highest RPN scores were subjected to corrective actions and the FMEA was repeated, showing reductions in RPN scores and resulting in improvement indices up to 5.0. We recommend risk analysis as an addition to the usual analytical validation, as the FMEA enabled us to detect previously unidentified risks.
authors.affiliation: National Institute for Public Health and the Environment, RIVM, Centre for Quality of Chemical-Pharmaceutical Products, Bilthoven, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: van Leeuwen
authors.forename: M J
authors.initials: MJ
authors.lastname: Nauta
authors.forename: D
authors.initials: D
authors.lastname: de Kaste
authors.forename: Y M C F
authors.initials: YM
authors.lastname: Odekerken-Rombouts
authors.forename: M T
authors.initials: MT
authors.lastname: Oldenhof
authors.forename: M J
authors.initials: MJ
authors.lastname: Vredenbregt
authors.forename: D M
authors.initials: DM
authors.lastname: Barends
mesh_terms: D019411:Clinical Laboratory Techniques; D003257:Consumer Product Safety; D004345:Drug Industry / Q000592:standards* / Q000639:trends; D006801:Humans; D019300:Medical Errors / Q000517:prevention & control; D008508:Medication Errors / Q000517:prevention & control; D011336:Probability; D018570:Risk Assessment / Q000379:methods; D012308:Risk Management / Q000379:methods; D017751:Safety Management; D019265:Spectroscopy, Near-Infrared / Q000379:methods