title: Cleaning verification: Exploring the effect of the cleanliness of stainless steel surface on sample recovery.
abstract: The parameters affecting the recovery of pharmaceutical residues from the surface of stainless steel coupons for quantitative cleaning verification method development have been studied, including active pharmaceutical ingredient (API) level, spiking procedure, API/excipient ratio, analyst-to-analyst variability, inter-day variability, and cleaning procedure of the coupons. The lack of a well-defined procedure that consistently cleaned coupon surface was identified as the major contributor to low and variable recoveries. Assessment of acid, base, and oxidant washes, as well as the order of treatment, showed that a base-water-acid-water-oxidizer-water wash procedure resulted in consistent, accurate spiked recovery (>90%) and reproducible results (Srel≤4%). By applying this cleaning procedure to the previously used coupons that failed the cleaning acceptance criteria, multiple analysts were able to obtain consistent recoveries from day-to-day for different APIs, and API/excipient ratios at various spike levels. We successfully applied our approach for cleaning verification of small molecules (MW<1000Da) as well as large biomolecules (MW up to 50,000Da). Method robustness was greatly influenced by the sample preparation procedure, especially for analyses using total organic carbon (TOC) determination.
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
authors.forename: Imad A
authors.initials: IA
authors.lastname: Haidar Ahmad
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Tam
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Duffield
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tarara
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, CA, USA. Electronic address: andrei.blasko@novartis.com.
authors.forename: Andrei
authors.initials: A
authors.lastname: Blasko
mesh_terms: D003902:Detergents / Q000008:administration & dosage / Q000592:standards; D004345:Drug Industry / Q000379:methods / Q000592:standards*; D004866:Equipment Contamination / Q000517:prevention & control*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000138:chemical synthesis; D013193:Stainless Steel / Q000032:analysis* / Q000592:standards*
chemical_list: D003902:Detergents; D004364:Pharmaceutical Preparations; D013193:Stainless Steel
keywords: Cleaning method development; Cleaning verification; Coupons; HPLC; RPLC; TOC