title: Implementation of highly sophisticated flow cytometry assays in multicenter clinical studies: considerations and guidance.
abstract: Flow cytometry is increasingly becoming an important technology for biomarkers used in drug discovery and development. Within clinical development flow cytometry is used for the determination of PD biomarkers, disease or efficacy biomarkers or patient stratification biomarkers. Significant differences exist between flow cytometry methodology and other widely used technologies measuring soluble biomarkers including ligand binding and mass spectrometry. These differences include the very heavy reliance on aspects of sample processing techniques as well as sample stabilization to ensure viable samples. These differences also require exploration of new approaches and wider discussion regarding method validation requirements. This paper provides a review of the current challenges, solutions, regulatory environment and recommendations for the application of flow cytometry to measure biomarkers in clinical development.
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sommer
authors.affiliation: 2Biomarker Laboratories, PPD Inc., Richmond, VA 23230, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Morales
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Groenewegen
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Müller
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Naab
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Gaetane
authors.initials: G
authors.lastname: Woerly
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Esther
authors.initials: E
authors.lastname: Kamphausen
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Helene
authors.initials: H
authors.lastname: Marsot
authors.affiliation: 2Biomarker Laboratories, PPD Inc., Richmond, VA 23230, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bennett
authors.affiliation: 2Biomarker Laboratories, PPD Inc., Richmond, VA 23230, USA.
authors.forename: Vellalore
authors.initials: V
authors.lastname: Kakkanaiah
authors.affiliation: 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vitaliti
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000097:blood*; D055808:Drug Discovery / Q000379:methods*; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D015337:Multicenter Studies as Topic / Q000379:methods; D054928:Validation Studies as Topic
chemical_list: D015415:Biomarkers