title: In situ monitoring of soil dissolution dynamics: a rapid and simple method for determining worst-case soils for cleaning validation.
abstract: A common approach utilized in validating the cleaning of multi-product equipment is to challenge the cleaning cycle with the hardest-to-clean, or "worst-case", soil. The worst-case soil is often determined through bench-scale experiments. These experiments can be tricky and time-consuming, especially when the dissolution dynamics of the soils are characterized by crossovers beyond the limit of visual detection. This paper describes a simple in situ method for monitoring soil dissolution dynamics and rapidly determining worst-case soils for cleaning validation. The method utilizes the real-time response of electrical conductivity to identify crossovers and to determine the optimal time for endpoint analysis. The results address the sensitivity and reproducibility of the method and the identification of critical experimental parameters. The dissolution dynamics of several parenteral products are compared.
authors.affiliation: Merck & Co., Inc., Vaccine Technology & Engineering, West Point, PA 19486, USA. rizwan_sharnez@merck.com
authors.forename: Rizwan
authors.initials: R
authors.lastname: Sharnez
authors.forename: Justin
authors.initials: J
authors.lastname: Lathia
authors.forename: David
authors.initials: D
authors.lastname: Kahlenberg
authors.forename: Sunil
authors.initials: S
authors.lastname: Prabhu
authors.forename: Michael
authors.initials: M
authors.lastname: Dekleva
mesh_terms: D004340:Drug Contamination / Q000517:prevention & control; D004345:Drug Industry / Q000592:standards; D004553:Electric Conductivity; D004866:Equipment Contamination / Q000517:prevention & control*; D006920:Hygiene / Q000592:standards*; D007267:Injections; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012989:Soil Pollutants / Q000032:analysis*; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D013997:Time Factors
chemical_list: D012989:Soil Pollutants; D012996:Solutions