Delivering Advanced Flow Cytometry

Solutions

Comprehensive Flow Cytometry

Providing you with the integrated solutions you require.

The importance of flow cytometry to the drug development process and clinical studies has received much attention in recent scientific literature. Recognizing the growing importance of flow cytometry in the drug development process, Covance has made a substantial investment in the technology. Our laboratories, located world wide, support each phase of the drug development process with the appropriate accreditation (Figure 1).

Our clients benefit from the close collaboration the flow cytometry laboratories within Covance - Central Laboratory Services (CLS), Discovery & Translational Services (DTS), and Toxicology. Working together, these three Covance business units have developed a model that allows Covance the ability to provide the integrated solutions our clients require. This integrated model allows us to expedite the transition of assays originally developed for pre clinical use, to validated clinical assays within Covance CLS.

DrugDiscovery Clinical

Target ID

Screening/Target

Validation

Characterizeand Select

ToxicityStudies

Clinical Trails

Launch/Phase IV

Discovery/Translational Toxicology Central Laboratory

Non-Regulated GLP and Non-GLP CAP/CLIA

Greenfield, Indiana Harrogate, United Kingdom Geneva, Switzerland

Indianapolis, Indiana

Shanghai, China

Singapore

Tokyo, Japan

Madison, Wisconsin

Münster, Germany

Pre Clinical

Figure 1

Since 1996, Covance CLS has performed flow cytometry for therapeutic areas such as CNS, Oncology, Infectious Dis-eases, and Autoimmunity.

All five Covance CLS laboratories are CAP/CLIA accred-ited, and equipped with two or more identical FACS Canto II instruments, to offer state-of-the-art flow cytometry test-ing. This technology, combined with the experience of our scientific experts, allows Covance CLS to work with you to identify and develop custom panels for your specific clinical trial needs.

The labs function as one virtual lab guided by three Ph.D. level scientists. In addition to standardized instrumentation, reagents, SOPs, and QC monitoring; data analysis for high complexity assays is centralized to ensure the greatest level of consistency.

Core Panel/Smart Panel ApproachOur panel designs are based on the core panel/smart panel approach, with common “anchor markers” (same antibody clone/same fluorochrome) to ensure • consistencyacrosspanels, • optimumsignal-tonoiseratio, • minimizedcompensationforsignaloverlap.The resulting smart panels can be validated more efficiently and at lower cost.

The BCOE flow cytometry laboratory has provided custom flow cytometry applications for drug development for over 20 years. The team’s broad expertise in de novo assay development includes diverse methods that incorporate complex ex vivo treatments, cellular activation and culture, and immuno-magnetic enrichment of rare populations, among others. Although not a regulated laboratory, this lab participates in CAP flow cytometry proficiency testing and follows “Good Research Practices” (SOPs for instru-ment calibration, training, data documentation, etc.) in order to provide both the quality assurance and flexibility clients demand in the discovery and translational phases of development.

Central Laboratory Services

Biomarker Center of Excellence (BCOE)

Flow scientists at Covance are active in professional cytometry societies including the Interna-tional Society for the Advancement of Cytometry (ISAC) and the Clinical Cytometry Society. Dr. Virginia Litwin of CLS is a co-chair of the American Association of Pharmaceutical Scientists (AAPS) PharmaFlow working group and a thought leader on flow cytometry assay validation and implementation of high complexity testing in clinical trials.

THE AMERICAS +1.888.COVANCE (+1-888-268-2623) +1-609.452.4440

EUROPE/AFRICA +800.2682.2682 +44.1423.500888

ASIA PACIFIC +800.6568.3000 +65.6.5686588

www.covance.com

© Copyright 2013, Covance Inc. BRODIS011-0413

BCOE Flow/Cell Capabilities Overview• Expertiseinde novo assay development, especially functional readouts, to measure target engagement and pharmacodynamic response• Specializinginadvancedapplicationssuchascellsignaling (intracellular phospho-proteins), natural killer cell and other immune function assays, and microparticle analysis.• Assaydevelopmentwithaccesstonormaldonoranddisease state samples under IRB approved process• Translationofresearch/exploratoryassaystosupportearly clinical development• Equipmentincludes:BeckmanCoulterGallios3laser/10color flow cytometer with available HyperCyt multi-well plate high throughputsampler,BDFACSCantoII3laser/8colorflow cytometer (same configuration as CLS and ED flow labs), Beckman Coulter 2 laser/5 color flow cytometer, Miltenyi autoMACS magnetic-based cell sorter

Good Research Practices and Flow Cytometry Validation• SOPsforinstrumentoperationandQC,training,data documentation, quality review, and more• Fit-to-purpose validation appropriate for high complexity testing

Covance offers strong flow cytometry capabilities across the spectrum of the drug development pathway. Differentiators for Covance include our strong scientific leadership, internal integration and state-of-the-art approach to flow cytometric assay development and validation. Our emphasis on process improvement allows us to meet client needs.

Like Covance CLS, Toxicology flow cytometry laboratories are located worldwide. The Toxicology laboratories provide assay development, validation and pre clinical testing. They have validated a wide variety of cell-based assays and immunopheno-typing markers in multiple species using both GLP and fit-for-

purpose method validation conventions. Toxicology flow cytom-etry laboratories continually collaborate with Drug Discovery and Clinical sites to ensure smooth transitions of flow methods as molecules move forward in the drug development process.

Early Development (Toxicology)

BCOE Research Interfaces

• Collaborative approach for assay development and validation to meet client needs

Service Line Integrated Research Examples

In Vivo Pharmacology

Flow cytometry endpoints added to efficacy models

Central Labs

Immune function assays performed on clinical trial subject PBMC

samples prepared and managed by CLS

GenomicsPhenotype and isolate rare

leukocyte subsets and prepare for RNA analysis

Immunology Services and

Antibody Products

Flow cytometry support for antibody and vaccine development

Early DevelopmentCollaborate on development of assays for GLP validation and

implementation

Cell Culture TeamCo-located to provide cell lines for in vitro testing and assay expertise