LTD brochure_EN_20150104

WuXi AppTec Laboratory Testing Division

Fully Integrated Solutions

"We provide a world class, fully integrated testing solution

enabling scientists to transform their ideas into the best

healthcare products, moving science from research bench to

hospital bed, in order to better serve our community.

We serve as a healthcare 'Silk Road', which enables advanced

technologies to enter the Chinese market effectively, by

leveraging our deep regulatory expertise and wide reaching

sales and marketing network."

As a key business within WuXi AppTec’s diversified portfolio,

the Laboratory Testing Division (LTD) is comprised of seven

business units (BUs), over 2,000 employees and operations in

Shanghai, Suzhou, Tianjin, Wuhan, Nanjing and New Jersey.

LTD's integrated services and solutions in pharmaceutical

development span from early screening to preclinical

development and into clinical sample analysis. Leveraging

other established WuXi businesses in MedChem, synthesis

and formulation, LTD is well positioned to enable customers

to accelerate their discovery processes and empower them to

bring new, innovative medicines to patients.Jason Liu, PhD

SVP & COO, Laboratory Testing Division

Jason Liu

Laboratory Testing Division


2

ASU

BIO

ONCO

IMMU

DMPK

BAS

TOX

MD

Global Compliance

2009

2010

2011

2012

2013

2014

2008 •Biological Animal Facility Received AAALAC Accreditation

•Analytical Laboratory Passed MPA Inspection

•Bioanalytical Laboratory Passed FDA Inspection

• Toxicological Animal Facility Received AAALAC Accreditation

• Toxicological Laboratory Received GLP Certificate from CFDA

• Biological hERG Laboratory Received GLP Certificate from OECD

• Biological Animal Facility Passed AAALAC Inspection

• Analytical Laboratory Passed CFDA Inspection

• Toxicological Laboratory Received GLP Certificate from OECD

• Toxicological Laboratory Passed CFDA Inspection

• Analytical Laboratory Passed MPA Inspection


• Biological Laboratory Passed OECD Inspection

• Toxicological Animal Facility Received “Exemplary” Commendation from AAALAC

• Analytical Laboratory Passed FDA Inspection


• Biological Animal Facility Passed AAALAC Inspection

• Toxicological Laboratory Passed FDA Inspection

• Toxicological Laboratory Passed OECD Inspection

2015


• Toxicological Animal Facility Passed AAALAC Inspection

Laboratory Testing Division3

• New Jersey Laboratory Passed FDA Inspection2004

Discovery Package

Device Package

Discovery Screening

LeadOptimization

Candidate Nomination

Discovery Screening

Lead Optimization

Candidate Nomination

Hit-to-Lead

BIO/ONCO/IMMU• In vitro efficacy• In vivo target engagement• In vivo pharmacology

DMPK• HTS/MTS• Physicochemical property

measurement• Permeability• Stability in biological

solutions• Metabolic stability

ASU• Analytical chemistry• Chiral SFC separation• Natural product extraction,

isolation and identification

CSU• Synthetic chemistry

BAS• Clinical chemistry• Immunogenicity• Large/small molecule

bioanalysis

Lead Optimization

TOX• Early diagnosis testing• Mini Ames

DMPK• PK• Permeability• Drug-drug and transporter

interactions• Metabolite ID

ASU• Analytical chemistry• Chiral SFC separation

(scale-up)

BIO/ONCO/IMMU• In vitro selectivity asssay• MOA• Early cellular toxicity assay• In vivo target engagement• In vivo pharmacology

CSU• Compound synthesis/MedChem

BAS• Biomarker analysis (soluble, cell,

tissue, genetic)• Large/small molecule bioanalysis

Medical Device Testing

4Laboratory Testing Division

ASU - Analytical Service UnitBAS - Bioanalytical ServicesBIO - Biology UnitCSU - Chemistry Service Unit (early-stage synthesis and MedChem)DMPK - Drug Metabolism and PharmacokineticsIMMU - Immunology

IND/NDA Package

Preclinical Clinical Market

Preclinical

Clinical

Market

Preclinical

Clinical

Market

CMC

ASU (Drug Substance and Drug Product)• Method development & validation• Compound characterization & batch release• Stability study• Regulatory CMC

STA (Drug Substance)• Process development• GMP API manufacturing

Safety

TOX• General toxicology• Genetic toxicology• Safety pharmacology• Reproductive toxicology

BAS• Clinical chemistry• Immunogenicity• Small/large molecure

bioanalysis

BIO/ONCO/IMMU• hERG assays

ADME

DMPK• Permeability• Plasma protein binding• RBC partitioning• DDI (CYP inhibition, induction, phenotyping)• Transporter profiling• Metabolite ID (in vitro/in vivo)• MIST studies• PK/bioavailability• Allometric scaling• Radiolabeled and unlabeled ADME• Tissue distribution (QWBA and QTD)• Route of excretion

BAS• Biomarker analysis (soluble, cell, tissue, genetic)• Small/large molecule bioanalysis (GLP-like/GLP)

PharmacologyBIO/ONCO/IMMU• Ligand binding• Receptor profiling• In vitro efficacy• In vivo efficay (PD)• MOA• Translational medicine

5

PDS (Drug Product)• Preformulation• Formulation

development• Clinical trial material

manufacturing


MD - Medical DeviceONCO - OncologyPDS - Pharmaceutical Development Services (drug product manufacturing and formulation development)STA - SynTheAll (API manufacturing)TOX - Toxicology

Analytical Development from Early to Late Phases

•Method development and validation for APIs and drug

products

•GMP/GLP release of early phase APIs

•GMP release of late phase and commercial APIs and drug

products

•Drug product manufacturing support

• Impurity/degradation characterization

Stability Studies

•For small molecule drugs and large molecule products

•API and clinical trial material (CTM) stability studies for

IND/NDA/ANDA

•Primary and registration stability studies (formal) as well

as accelerated and long-term stability studies

•Commercial stability study

•Dedicated sample management, lab testing and

documentation

WuXi Separation Center

•Chiral and achiral separation by SFC and HPLC

•Research & development or GMP mode

•From small (mg) to large (hundreds of kg) scale

Center of Natural Products

•Expansive natural product library with diverse structures

•Extraction, isolation and identification of natural products

Impurity Isolation and Identification

• Isolation and identification of impurity/degradation

products

Regulatory CMC

•For global and China submission

•Full CMC package by dedicated technical writing group

Physicochemical Characterization & Excipient Release

•Solubility, logP/logD and pKa

•Heavy metal by ICP-MS

•HRMS, NMR (1D/2D), LCMS, GCMS, IR and UV

•ROI, DSC, TGA, DVS, XRPD, PLM, elemental analysis

•Refractive index (RI), conductivity, viscosity, optical

rotation, turbidity, specific gravity, bulk density etc . . .


Analytical Service Unit (ASU)End-to-end analytical service provider from discovery to commercialization

One of the largest stability storage and testing facilities in the world

The largest chiral and achiral separation facility in China

FDA, CFDA & MPA-compliant

7 Laboratory Testing Division

8

In Vitro Screening Platform

•Assay development and transfer

•Kinase, GPCR, transporter and ion channel panels

•Capable of radioactive assays involving: 3H, 14C, 32P,

33P, 35S & 125I

Infectious Disease and Immunology

• In vitro and in vivo antiviral/antibacterial platforms

•Clinical study support

•Vaccine & biologics services

• In vitro and ex vivo immunology assays

• In vivo immunology animal models

Central Nervous System and Pain

• In vitro and in vivo pharmacology

• Ion channel assays

• In vivo electrophysiology

•Receptor occupancy

• In vivo disease models

Cardiovascular and Metabolic Disorders

•Regular (monthly) supply of DIO mice

•Pharmacology of obesity, diabetes, dyslipidemia

and thrombosis

•Telemetry hypertension and angina pharmacology

Early Stage Safety Assessment

•GLP and non-GLP hERG assays

•Cardiac safety panel screening assays

•CNS safety behavioral models

•Cardiomyocyte action potential measurement

•Purkinje fiber action potential measurement

•Guinea pig MAP

•Telemetry measurements of ECG and blood

pressure

Structural Biology and Modeling

•Protein expression, purification and crystallization

•Off-the-shelf protein crystallization

•Crystal structure determination

•Fragment-based drug discovery (FBDD)


9

AAALAC and OLWA-certified animal facility, OECD-certified GLP electrophysiology lab, CLIA-compliant molecular testing lab

A leading biological CRO in infectious disease, CNS and pain, immunology and cardiovascular and metabolic diseases

Fully integrated with MedChem programs delivering over 20 preclinical drug candidates since 2008

Biology (BIO)


AAALAC and OLWA-certified animal facility

Largest collection of Asia-prevalent PDX models

IND-enabling in vivo data for CFDA & FDA filing

Genome-wide screening with CRISPR libraries

The world's 1st integrated online tumor model database

Oncology (ONCO)

http://onco.wuxiapptec.com


CRISPR

•Generation of cell lines and mouse models with

knockout and knockin mutations

•Genome-wide knockout screening for target ID

(human and mouse cell lines)

•Target validation for oncology, immuno-oncology &

rare genetic diseases

Tumor Models

•~150 cell line-derived xenograft (CDX) models

•24 bioluminescence imaging orthotopic & metastatic

tumor models

•~1000 PDX models available, 509 models molecularly

profiled and annotated, 220 models currently in life

•The world's 1st integrated tumor models database:

OncoWuXi

•The largest collection of PDX models of Asia-

prevalent cancer types

•Drug-resistant PDX models for targeted cancer

therapeutics

•~70 primary cancer cell lines derived from PDX

models

Cancer Immunotherapy

•~50 syngeneic tumor models

•TIL, Treg and cytokine focused immunoassays

•T-cell /cancer cell mechanistic and functional assays

•Validated with PD-1/PD-L1 antibody

Translational Science

•Tissue bank with over 2,500 human tumor samples

•Patient selection biomarker discovery by NGS using

Illumina HiSeq X10

•Simulated Phase II-like trials with PDX panels

•Focal radiation, standard of care & combination

therapy

•MOA based PD assays

Tumor Cell Biology

•Biochemical assays

•Cell-based mechanistic and phenotypic assays

•Tumor cell chemo-sensitivity assays

•Cancer stem cell (CSC) platform


Autoimmune diseases and inflammatory animal models

•Rheumatoid arthritis (RA) models

•Multiple sclerosis (MS) models

•Delayed type hypersensitivity (DTH) models

•Psoriasis model

AAALAC-accredited SPF animal facility

CLIA certification and GCP-compliance

Partnerships with world-renowned pathology laboratories

Histopathology core equipped with automated high throughput systems

Advanced flow cytometry core with 18-color analysis and sorting capability

Immunology Center (IMMU)


• Inflammatory bowel disease (IBD) model

•Gout models

•LPS-induced airway inflammation in Wistar rats

•ConA-induced cytokine model in mice and rats

Cancer Immunology Platform

•TM (tumor microenvironment) analysis for

immunoscore by FACS, IHC and IF

•Lymphoid tissue and peripheral blood analysis

•Lymphocyte activation / functions

•Cytokine and Chemokine analysis

•Adoptive T cell therapy


Biomarker Service

•Tissue-based biomarkers – pathology lab

•Cell-based biomarkers – flow cytometry lab

AAALAC, FDA and CFDA-inspected

A comprehensive ADME and PK service provider from HTS through NDA filing

Integrated with Biology and MedChem for streamlined lead optimization

Delivered 12 preclinical drug candidates in 2014

DMPK


Early and Definitive In Vitro ADME

•Physicochemical characterization

•Permeability

•Metabolism and clearance

•CYP inhibition/induction/phenotyping

•Plasma protein binding and RBC partitioning

•Transporter drug-drug interactions

•Metabolite identification

Early and Definitive In Vivo ADME

•All major animals from mouse to cynomolgus monkey

•A variety of common & customizable surgical models

•Metabolite identification and quantitation

•Full PK profiling and modeling for all species

• Intravenous, oral gavage, intramuscular, subcutaneous,

intraperitoneal, transdermal, duodenal, intranasal

instillation, intrathacheal instillation and sublingual

dosing

•Blood, plasma, urine, feces, bile, CSF, lymph and tissue

sampling

•Radiolabeled ADME: mass balance, routes of excretion (14C

and 3H)

•Tissue distribution:QWBA (quantitative whole-body

autoradiography) and QTD (quantitative tissue dissection)



Small Molecule Bioanalysis

•Assay development, validation and sample analysis using LC-

MS/MS (SCIEX, Waters and Thermo platforms)

Large Molecule Bioanalysis

•Assay development, validation and sample analysis for drug

PK, ADA and Nab assays using immunochemistry techniques

(ELISA, MSD, Gyros) or LC-MS

Large Molecule Assay Reagent Development

•Drug-specific mAb and pAb generation, purification, labeling

and characterization

Biosimilar Studies

•Free-to-use methods for the top biosimilars

Biomarker Analysis

•Assay development, validation and sample analysis for

soluble, cell and tissue biomarkers (Luminex, FACS, Ventana

Discovery Ultra)

Central Lab Services

•Safety testing, clinical trial supplies, sample logistics and

storage for clinical trials

The largest bioanalytical lab in Asia for biologics

The only bioanalytical lab in China inspected by the FDA, EMA, OECD and CFDA; US

Lab FDA inspected since 2004

In-house, custom reagents for large molecule assays

Ultrasensitive pg/mL LLOQs in small molecule LC-MS/MS

Synthesis of stable labeled internal standards or PI/PII metabolites

Bioanalytical Services (BAS)


AAALAC, FDA, OECD and CFDA-inspected

A premier toxicology service provider in China

The 1st CRO in China with an ACLAM-certified veterinarian

Comprehensive toxicology packages supporting China and global IND/NDA filings

Toxicology (TOX)

General Toxicology

•Early diagnosis testing (EDT)

•Dose-ranging or MTD studies

•Single dose (acute toxicity)

•Repeat dose (subacute, subchronic and chronic)

Developmental and Reproductive Toxicology

•Dose-ranging study on embryo-fetus development

in rats, rabbits

•Definitive study on embryo-fetus development in

rats, rabbits with TK (Seg II)

•Study on fertility and early development to

implantation in rats (Seg I)

Genetic Toxicology

•Ames assay

•Chromosomal aberration assay (CHO-WBL cell and

human lymphocyte)

•Micronucleus assay (rat and mouse)

•Micronucleus assay (CHO-WBL cell)

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Safety Pharmacology

•CNS (rodent and non-rodent)

•Respiration (rodent and non-rodent)

• Implanted cardiovascular telemetry (dog, NHP,

minipig)

•Non-invasive DSI JET assessments for biologics

•Fully validated DSI Ponemah system for data

collection and analysis

•hERG assay via manual patch clamp (Biology)

Immunotoxicology

•Tissue cross reactivity (human tissues)

• Immunogenicity/ADA

• Immunophenotyping

•T-cell-dependent antibody responses (TDAR)

Anatomic and Clinical Pathology

•Toxicological or immunopathology


Biocompatibility Test

•Cytotoxicity test

• Irritation

•Sensitization

•Hemocompatibility

•General toxicity test

•Pyrogenicity

•Genetic toxicology

• Implantation

Chemistry Test

•Analytical chemistry test

•Ethylene oxide test

•Extractable/Leachable programs

•Physical properties testing

•Wet chemistry

Medical Device (MD)

19

Microbiology Test

•Controlled environment test

•Growth promotion test

•BI enumeration

•BI sterility test


End-to-end testing services including material screening, product design and regulatory testing

Support for Chinese and international clients to register their product with the China Food and Drug Administration (CFDA) and for Chinese clients to register their products outside of China

Fully compliant with FDA, OECD and CFDA GLP requirements

AAALAC-inspected animal facilities

ISO/IEC 17025(under evaluation)

LTD

2015

08B2Shanghai

Tel: +86(21) 5046 5122Fax: +86(21) 5046 1000Email: [email protected]

Contact usU.S./EuropeTel: +1(609) 799 2295Fax: +1(609) 799 7497Email: [email protected]

New Jersey

107 Morgan Lane PlainsboroNJ 08536 U.S.A.

Nanjing

1 Hengfei RoadEconomic & Technological Development ZoneNanjing 210038 China

Suzhou

1318 Wuzhong AvenueWuzhong DistrictSuzhou 215104 China

Shanghai

288 Fute Zhong RoadWaigaoqiao Free Trade ZoneShanghai 200131 China

ltd.wuxiapptec.com

Wuhan

666 GaoXin Road,Wuhan East LakeHi-tech Development ZoneHubei 430075 China

Tianjin

111 Huanghai RoadTianjin Economic-TechnologicalDevelopment Area (TEDA)Tianjin 300457 China

Documents

LTD brochure_EN_20150104