Qps Presentation

QPS is a GLP-compliant CRO that supports Discovery, Preclinical, and Clinical Development

Services:• Bioanalysis• DMPK• Biomarker• Early Phase Clinical Research

Testing Facilities:• Bioanalysis/DMPK/Biomarker – Newark, DE (QPS, LLC)• Bioanalysis – Taipei, Taiwan (QPS Taiwan Company Ltd)• Early Phase Clinical Research – Springfield, MO (Bio-Kinetic Clinical

Applications, LLC)

Regional business development offices are maintained on the East Coast, the West Coast, and the Midwest

Quality Performance Service

QPS QPS Taiwan

Bio-Kinetic


QPS, LLC

Founded Nov 1995

Senior Management from Pharma/Biotech

4 Facilities located in Newark, DE

• GLP• 48,800 sq. ft. total• 19,000 sq. ft. LC/MS/MS & ELISA• 23,500 sq. ft. ADME/WBA• 2,500 sq. ft. Molecular Biology• 31 Mass Spec (Triples & Ion Trap)

Quest Pharmaceutical Services Taiwan Company Ltd.

• Founded in Jan 2004• 8,500 sq. ft. GLP Bioanalytical • 4 Triple Quadrupoles

Quality You ExpectService You Trust

Turnaround You Need


Quality – Performance – Service

Quest Pharmaceutical Services and Bio-Kinetic Clinical Applications merged in early 2008 to form a company based on our mutual beliefs and practices on QUALITY, PERFORMANCE, and SERVICE.


Clinical Package

Support Phase I Clinical Development for NCEs and Biologics

Design the study

Prepare the study protocol, informed consent, and case report forms

Conduct the clinical phase of the study

Bioanalysis of biological samples • (LC/MS/MS, ELISA, Immunogenicity, and Hybridization-ELISA)

Biostatistics and clinical data management

Conduct PK/PD data analysis and modeling

Prepare PK/PD report will be appended to the clinical study report

Population PK or PK/PD data analysis capability is also available

Prepare and publish clinical study report

Service

Springfield, Missouri

QPS Bio-Kinetic is located just 10 minutes from the Springfield-Branson Regional Airport


Quality

Established Clinical Site• Phase I – IV• Founded in 1994• Over 800 studies completed

State-Of-The-Art Facility• Five (5) Study Units on One Campus• 240 Beds

Performance

State-Of-The-Art Facility• Separate secure pharmacy, retention area, examination

rooms, dosing, and phlebotomy stations• State-of-the-art refrigerated centrifuges• High speed micro centrifuges

Performance

State-Of-The-Art Facility• Local clinical lab provides most results within 24 hours a

day, 7 days a week• Laminar flow hoods• -70˚C and -20˚C freezers • NIST calibrated temperature recording devices in

refrigerators and freezers

Performance

State-Of-The-Art Facility• 24-hour security and monitoring systems• Secure archive/ document storage• FM 200 Gas fire suppression • Automatic natural gas powered generators for power

backup• AEDs

Performance

State-Of-The-Art Facility• Fully equipped ECG and vital sign monitoring• State-of-the-art self-interpreting electrocardiographs

Service

Population Specialties• Healthy normal males • Healthy normal females• Healthy normal birth control free females• Healthy postmenopausal women • Healthy geriatric males and females• Other select populations

Service

Administration Expertise:• Oral• Intravenous• Intramuscular• Intradermal • Subcutaneous• Buccal• Transdermal — cream, gel, patch• Vaginal — cream, gel, suppository• Suppository• Intranasal• Intrauterine

Service

QTC14%

Vaccine5%

PD4%

Other1%

Steady State17%

Food Effect10%

RDT2%

DDI5%

BE15%

BA27%

Type of Study2005 to 2009

QTC

Vaccine

PD

Other

Steady State

Food Effect

RDT

DDI

BE

BA

Performance

Examples of Study Experience (between 2004 – 2009)• 24 Vaccine Trials

» 1 Hepatitis B

» 1 Japanese Encephalitis

» 1 Yellow Fever

» 2 West Nile

» 4 Dengue Fever

» 5 Small Pox

» 10 Flu

• 43 Postmenopausal Studies• 36 Geriatric Studies• 19 Birth Control Studies• 12 Cardiac Safety Studies

Service

Collaboration with Quintiles for TQTc• Full service TQTc offering • Ability to conduct large cohorts• High throughput paperless system• 24/7 monitoring by cardiologists• ECG data management from initiation through submission

to the FDA ECG Warehouse

Quality

Clinical Staff Experience• Four (4) Principle Investigators

» Two (2) started in 1994

» One (1) started in 2000

» One (1) started 2005

• Clinical Staff Experience» 6+ years average length of employment

» Less than 5% staff turnover rate

» Leadership team averages over 15 years

of experience managing clinical trials

Quality

Audit Experience• Twelve (12) FDA Audits

» Ten (10) Clinical Sites

» Two (2) IRBs

» One 483 (Sept. 2003)

» 16 Studies (Most recent- Aug. 2009)

Performance

Rapid Recruitment• 500,000 Metropolitan Area Population• 40,000 College Student Population• Over 3 hours from nearest Phase I units• Large Database of High Quality Subjects

» Less than 5% drop out rate

» Over 20,000 registered subjects in database

» Fill 80% of studies exclusively from database

Performance

Rapid Recruitment• Multi-tiered Outreach Effort

» Direct

– Email & Mail

– Phone Calls

» Internet

– New Interactive Website

o QPSBioKinetic.com

– Community websites

– Interviews

Performance

Rapid Recruitment• Multi-tiered Outreach Effort

» Community Events

– Job Fair

– University Social Events

– Promotional Events

– Sponsorship

» Mass Marketing

– Billboards & Buses

– TV & Radio

– Newspaper Ads

» Referral Programs

– Participants

– Local Business

Service

Rapid Recruitment• Patient Stratification

» Identification of Poor or Extensive metabolizers

» Genotyping (CYP2C9, CYP2C19, CYP2D6, NAT1, NAT2, ApoE, etc.)

» 48-72 hours turnaround

Quality

Individualized Study Preparation• Protocol Training

» Initiation Visit

» Protocol Review

» Walk Through Meetings– “Dry Runs”– Protocol Training– AE Preparation and Review– Study Events Review

» Weekly Staff Review Meeting– Protocol Training– GCP Training– Review Study Preparation– AE Preparation and Review

» Custom Communication Plan

Performance

Study Integrity» Concise SOPs

» Protocol Adaptable Processes

» Continual Staff Training

» On-Time Study Events

» Accurate Sample Collection

» Thorough Sample Reconciliation

GLP Compliant• Follow FDA Crystal City Guidelines, OECD, MHLW• “Incurred Sample Reproducibility” White Paper

Discovery, Preclinical, and Clinical programs• Biological matrices, Target organs, Dosing solutions, CMC

Rapid Assay Development, Validation, Sample Analysis

“N-in-1” or Discrete Analysis

Automated Sample Preparation

Chiral Separations

Extensive Validated Assays• HIV, Pain, Oncology• Anti-infectious

M1

M2

M3

M4

M5

M6

IS1 IS2

IS3

LC/MS/MS

Service

Bioanalysis Services

Drug Concentration and Dosing Solution Concentration• Small Organics, Polypeptides

» LC/MS/MS, LC-UV, LC-Flu

• Proteins and Vaccines» ELISA and Immunogenicity

• Oligonucleotides» Hybridization-ELISA, LC/MS/MS, LC-UV

• Radiolabeled Mass Balance Studies» LC/RFD (Radio-Flow Detector)

Plasma Concentration Profiles in Intact Rats Following Intravenous

Administration of 5 mg/kg

0.001

0.010

0.100

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10.000

100.000

0 4 8 12 16 20 24

Time (h)

µg

Eq

uiv

ale

nts

/mL

or

µg

/mL

.

Total Radioactivity, µgequivalents/mLTest Article, µg/mL

Plasma Concentration Profiles in Intact Rats Following Oral Administration of 20 mg/kg

0.001

0.010

0.100

1.000

10.000

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Time (h)

µg

Eq

uiv

ale

nts

/mL

or

µg

/mL

.

Total Radioactivity,µgequivalents/mLTest Article, µg/mL

Plasma Concentration Profiles in Bile Duct-Cannulated Rats

Following Oral Administration of 20 mg/kg

0.001

0.010

0.100

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10.000

100.000

0 4 8 12 16 20 24

Time (h)

µg

Eq

uiv

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/mL

or

µg

/mL

,

Total radioactivity, µgequivalents/mLTest Article (µg/mL)

Service

QPS(US) GLP LC/MS/MS Facility

24 Triple Quadrupoles (31 US total)• 19 Sciex API 4000s• Shimadzu VP-series LCs; Agilent 1100 LCs • Waters UPLCs• Leap HTS/PAL and HTC/PAL injectors• 2 Cohesive Technologies ARIA Systems

2 UV (VWD) and 3 Fluorescence Detectors

Sample Prep• Sample Receipt/Inventory Lab• 4 General Sample Prep Labs• P2 Lab for HIV, HBV, HCV samples• 3 Tomtec Quadra 96 for 96-well sample prep

Service

Typically get a Study Underway within 2 – 4 weeks with• receipt test material(s) • signed protocol

Validate assay within 2 – 4 weeks

PK/TK study with 1500 samples• preliminary data within 2 weeks of sample receipt• audited data within 2 weeks of prelim data• 48 hr. turnaround, if needed for dose range/escalation study

QPS(US) GLP Bioanalysis Timelines

Performance

QPS Clinical PK/PD Capabilities

Contribute to the design of a clinical PK/PD study & the preparation of the study protocol

PK/PD data analysis and report preparation (including population PK & PK/PD analysis, PK & PK/PD compartmental modeling, & non-compartmental PK & PK/PD data analysis)

Contribute to the preparation of the CSR

Service

PK/PD Data Analysis Software

PK/PD Analysis: WinNonlin & NONMEM

Statistical Analysis: PCSAS, S-Plus, & nQuery

Graphing: SigmaPlot & S-Plus

Simulation: WinNonlin, NONMEM, & S-Plus

Population PK/PD ModelingA Fundamental Tool to Characterize Exposure-Response Relationships

Time (h)

Dru

g C

once

ntr

atio

n

0 2 4 6 8 10 12

0.0

0.0

20

.04

0.0

6

Extensive/Sparse PKCovariates

Time (h)0 1 2 3 4 5 6

Nonlinear Mixed Effects Modeling

ExposureExposure

Exposure

Eff

ect(

%)

0 2 4 6 8

02

04

06

08

01

00

Efficacy

Exposure

pro

bal

ity(D

LT

)

0 2 4 6 8 10 12

0.0

0.2

0.4

0.6

0.8

1.0

Safety

Dosage RegimenDetermination

Dru

g C

onc

ent

ratio

n0.

00.

050.

100.

150.

20PK/PD PK/PD

Service

Why QPS?Good Critical Mass – Reasonably Sized and User FriendlyResponsive and On TimeDirect Access to Key PersonnelFocused Science and Extensive Experience in Drug DevelopmentSpecialized CRO: Preclinical DMPK & Clinical Drug Metabolism, Clinical Pharmacology/Pharmacokinetics/Pharmacodynamics

• Drug Analysis» LC/MS/MS, ELISA, Immunogenicity, Hybridization-ELISA, LC/RFD

• Comprehensive Discovery and Preclinical ADME Studies• Drug Metabolism: Metabolite Profiling & Identification in Animals &

Humans• Biomarkers and Cell-based Assays

» Protein, Biochemical, and Pharmacogenomics/Pharmacogenetics

• Phase I Clinical Pharmacology/PK/PD• Health Volunteers


Performance

91% of the time QPS has been the low cost providerIn cases where the sponsor has shared competitor’s cost information or from participation on online auctions.

Large subject database• Lower recruiting costs

Lower Cost of Living• Lower direct business costs• Lower subject stipends

Established Business• Process efficiencies• Single location efficiencies (staffing, operations, logistics)• Experienced, flexible staff

Performance

Recent Examples of Performance• Study 11708

» 1242 Subjects enrolled in 4 weeks– Aged 40 to 90– 80% over the age of 60 per protocol

» 16,160 Samples processed and shipped on time

• Study 11508» 90 postmenopausal subjects recruited in 4 weeks

» Conducted over holiday weekend on time

• 7 Studies in same compound» 116 to 140 subjects each

» All subjects naïve to compound

» Returns out to 3 months

» 50/50 male/female

» Single IM injection

Service

Commitment to Customer!• Highly experienced staff works to obtain results quickly, on

time and on budget• Work with you to meet your objectives• Minimize your costs• Recruit and start your study fast and full• We keep you updated every step of the way

Your Success is Our Success!

Quality

"At QPS Bio-Kinetic, you can expect the highest quality and reliable services for your Phase I studies. QPS Bio-Kinetic employs dedicated and experienced people to perform your studies.”

— Sheela M.

Associate Director, QA

“I have found [QPS] Bio-Kinetic to be a highly professional organization with the ability to be flexible and responsive to the needs of the clinical program.”

— Nicholas P.

Associate Director, Early Development

“QPS Bio-Kinetic has the most experience of any Phase I unit in the industry. They have highly-trained, long-term personnel who are not only technically expert but also understand the importance of your study. They have the equation for guaranteed success. I always recommend QPS Bio-Kinetic to my colleagues".

— Rick S.

CEO

Quality

“Our company has placed studies at QPS Bio-Kinetic for over 10 years, including the key pharmacokinetic study assessing Drug X components, as well as many of our postmenopausal women, Drug Y pilot bioavailability studies, and all of our pivotal bioequivalence studies.

One wouldn't normally think of Springfield, Missouri, as a major CRO site, but the types of subjects they continually enroll are just solid, middle-class citizens with excellent retention for a clinical study.

For our pivotal Drug Y BE studies, we routinely enroll over 70 postmenopausal women subjects and no other site in this country or EU can enroll and dose them in one day, as can be done at QPS Bio-Kinetic. QPS Bio-Kinetic is planned as a site for all future Drug Y BE studies. Having served on the Drug Y team and been involved in many management presentations, there is simply no way we can make our timelines and meet our project objectives without using this site.”

— Phil M.

Assistant VP of Clinical Pharmacology

Quality

“When we look for clinical research sites, we prefer smaller organizations that understand the unique pressures of optimizing speed, quality and price we face as a small company. We demand they be trustworthy, can perform the protocol as directed, are able to communicate study progress and are focused on client service.

I have worked with QPS Bio-Kinetic for many years, in particular for BE/BA, DDI and cardiac safety studies. Because of their experienced staff, training and detailed processes, I am confident I can count on qualified study participants, quality data and PK samples to be drawn on time.

I trust QPS Bio-Kinetic to tell me when they don’t have the capacity to perform my study according to my specifications or timeline. Based on their history of meeting my expectations and my trust in the QPS Bio‑Kinetic staff, QPS Bio-Kinetic has become my first choice as a clinical site.”

— Jim M.

Senior Director, Clinical Development

Ligand Binding AssayGLP Compliant –

• FDA Crystal City Guidelines, Pharma Research 2006 White Paper• “Incurred Sample Reproducibility” White Paper

Discovery, Preclinical, and Clinical programs• Biological matrices, Target organs, Dosing solutions

PK Drug Concentration / PD Biomarker Assessment• Assay Development/Validation• Sample Analysis

Immunogenicity• Assay Development/Validation for different classes of Antibodies (IgG, IgM, etc.)• Screening samples for positive response• Confirmation for samples displayed positive response• Titer ‘confirmed’ samples for the relative intensity of the immunogenicity• Design bioassay for measuring neutralizing antibodies

Service

QPS(US) ELISA/LBA Facility

Plate Readers• 4 Spectramax PLUS384

• Versamax 96-well reader• Lmax Chemluminescence reader• Gemni Fluorescence reader• MSD® ECL Platform (SECTOR PR100, Imager 6000)• Perkin Elmer Top Count® NTX

WATSON LIMS System v 6.4Sample Prep

• 2 Immunochemistry Labs• Cell Culture Lab

Meso Scale Diagnostics, LLC

Service

QPS(US) Additional Biomarker Facility

Bead-based MultiPlex• 2 BioRad Bioplex®

Automated ELISA• 2 IMMULITE®

Molecular Biology Equipment• Qiagen BioRobot Automated Sample Processing System (MDx) • Qiagen TissueLyzer• NanoDrop ND-1000 Spectrophotometer• Agilent 2100 BioAnalyzer• Biotage Pyrosequencing PSQ HS 96 SNP System • ABI 7900HT TaqMan RT- PCR System (TLDA, 96-well plate)• Affymetrix GeneChip Microarray System with 7G Upgrade• Ultra Lum Discovery 12iC Molecular Imaging & Analysis System

Sample Prep• 4 Molecular Biology Labs• Tissue Culture Lab

Service

DMPK Services

Discovery ADME Screen

Drug Candidate Selection Studies

IND/NDA-filing Studies• Animal Pharmacokinetics• In vitro/In vivo Metabolism• In vitro/In vivo Protein Binding• Tissue Distribution (QWBA)• Clinical PK/PD Modeling

Preclinical ADME Summary for IND submission

Compound A in Rats

0.1

1.0

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10000.0

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Time (hours)

Con

cent

rati

on (

ng/m

L)

CSFPlasma

Compound B in Mice

1

10

100

1000

0 5 10 15 20 25 30Time (hours)

Con

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(n

g/g)

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Plasma

Service

Comprehensive ADME StudiesAnimal Pharmacokinetics

• Single and Multiple Dose Pharmacokinetics, Dose Proportionality, and Absolute Bioavailability

• Mass Balance/Excretion• Formulation Optimization and Mechanistic Studies with different dose administration

routes

In vitro/In vivo Metabolism• In vitro Metabolic Stability in Animal and Human Hepatic Preparations• In vitro Inhibition in Human Liver Microsomes• In vitro Reaction Pathway Profiling• Ex vivo Induction in Animal Hepatic Preparations and In vitro in Human Hepatic

Preparations• Metabolite Profiling & Identification

In vitro/Ex vivo Protein Binding; RBC/Plasma Distribution

Tissue Distribution• Quantitative Whole-Body Autoradiography (QWBA)• Microautoradiography and Discovery QWBA

Service

QPS(US) ADME FacilityVivarium – focused on mouse and rat with 9 rodent rooms

• Triple cannulated animals for special models and in situ CSF• > 200 Metabolism cages

In vitro Cell Culture Lab

Dedicated Bioanalysis/Metabolism Equipments• 5 Analytical Labs for dose formulation and sample prep• 7 Mass Spec (6 API 4000s, LTQ ProteomeX)

» Shimadzu VP-series LCs, Agilent 1100 LCs; LEAP HTC/PAL injectors

• Tomtec Quadra 96 for 96-well sample prep• 4 Radioactivity Detectors

2 Autoradiography Labs• Leica CM 3600 Cryomacrotome• Leica CM 3050 S Cryomicrotome• Leica Vibratome 9800• Molecular Dynamics Typhoon 9410• Imaging Research MCID Elite System

Service

QPS(US) Licenses & Permits

AAALAC Accreditation

OLAW Assurance

ABC License

NRC License for Radiochemicals

• (3H, 14C, 32P, 33P, 35S, 45Ca, 51Cr, 90Y, 99mTc, 111In, 125I, 188Re)

DEA Registration for Scheduled Controlled Substances (Schedule I – V)

CLIA Certification

CDC Permit – Export/Import Primate samples

Federal Fish & Wildlife Permit

Quality You ExpectService You Trust

Turnaround You Need

Service

Approved by Taiwan’s Department of Health as a qualified CRO

QPS Taiwan / QPS(US)• Same Set of SOPs• Same Set of Laboratory Procedures• Same High Quality Standard

GLP LC/MS/MS• NCEs and non-proprietary compounds for US, European, and Local

Pharmaceuticals and Biotechnology Companies• Generic compounds for local Generic Companies

Pilot BA/BE Studies in collaboration with the Taipei Clinical Research Center (part of Taipei Medical University Hospital)

Discovery Dog PK Studies with our in-life Affiliate – DCB Taiwan

QPS Taiwan Services

Service

Study Management

Bioanalytical/Immunoanalytical/Biomarker• Design and Perform Studies• Schedule Studies as per Protocol• Review Sample Inventory

» Follow-up with sponsor & study site if discrepancy occur

• Plot data to reveal possible trend» Flag discrepancy for Sponsor review

Discovery ADME Screen

Drug Candidate Selection Studies

IND/NDA-filing ADME Studies• Design, Manage, and Perform Studies• Review, Prepare Study Reports, and Preclinical ADME Summary for IND

submission

Service

Clinic plus Bioanalysis Biomarkers

needed?

Receiver Review RFP

Generate Proposal, Internal

Review/Approval, f/b Issuance to Sponsor

Yes Receiver Distribute RFP to relevant Proposal

Distribution List

No

Individual P&L Center Generate Proposal(s) f/b

Internal Review

QPS Bio-Kinetic – Combine Proposals into a

Single QPS Proposal

Proposal Accepted?

End. Ask for Feedback

No

YesProject Manager Needed?

Decide on Project Manager, Study Monitor, Principle Investigator(s)

Yes

QPS Bio-Kinetic and QPS Bioanalysis parallel

Internal Process

QPS Bio-Kinetic – Conduct the clinical

phase

QPS Bio-Kinetic – Ship Clinical Samples

QPS Bioanalysis/Biomarker – Receive Clinical Samples

QPS Bio-Kinetic – Internal Process & Clinical

Summary Generation

QPS Bioanalysis/Biomarker –

Conduct Sample Analysis

QPS Bioanalysis/Biomarker –

Internal Process & Report Generation

QPS WHO – Combine Both Reports into a Single QPS Report

Report Issuance for Sponsor Review

Sponsor send RFP to QPS (any organization)

Internal Review/Approval, f/b Issuance to Sponsor

Decide on Study Monitor, and Principle

Investigator(s)

No

Process Map: Clinical with Bioanalysis/Biomarker RFP

Documents

Qps Presentation