title: Quantitative risk modeling in aseptic manufacture.
abstract: Expedient risk assessment of aseptic manufacturing processes offers unique opportunities for improved and sustained assurance of product quality. Contemporary risk assessments applied to aseptic manufacturing processes, however, are commonly handicapped by assumptions and subjectivity, leading to inexactitude. Quantitative risk modeling augmented with Monte Carlo simulations represents a novel, innovative, and more efficient means of risk assessment. This technique relies upon fewer assumptions and removes subjectivity to more swiftly generate an improved, more realistic, quantitative estimate of risk. The fundamental steps and requirements for an assessment of the risk of bioburden ingress into aseptically manufactured products are described. A case study exemplifies how quantitative risk modeling and Monte Carlo simulations achieve a more rapid and improved determination of the risk of bioburden ingress during the aseptic filling of a parenteral product. Although application of quantitative risk modeling is described here purely for the purpose of process improvement, the technique has far wider relevance in the assisted disposition of batches, cleanroom management, and the utilization of real-time data from rapid microbial monitoring technologies.
authors.affiliation: Sterility Assurance Leader, Eli Lilly & Co., Indianapolis, IN 46221, USA. tidswell_edward@lilly.com
authors.forename: Edward C
authors.initials: EC
authors.lastname: Tidswell
authors.forename: Bernard
authors.initials: B
authors.lastname: McGarvey
mesh_terms: D000465:Algorithms; D004339:Drug Compounding; D004345:Drug Industry / Q000379:methods* / Q000706:statistics & numerical data; D015233:Models, Statistical; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000592:standards*; D011786:Quality Control; D012306:Risk; D012307:Risk Factors; D013242:Sterilization / Q000706:statistics & numerical data*
chemical_list: D004364:Pharmaceutical Preparations