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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
Quality Performance Service
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
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.
Quality Performance 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 Performance Service
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
1.000
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
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 Bile Duct-Cannulated Rats
Following Oral Administration of 20 mg/kg
0.001
0.010
0.100
1.000
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)
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
Quality Performance Service
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
10.0
100.0
1000.0
10000.0
0 2 4 6 8 10
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
cen
trat
ion
(n
g/g)
Brain
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