Laboratory and Clinical Services
Clinical
Biometrics
CMC
DMPK
Bioanalytical
1
15+ Years of Strong Growth
2004
Company Founded
by Dr. Song Li
Opened
Shanghai,
China office
Opened Labs
in Green Valley
PA
2001
2014
2008
Expanded &
Relocated HQ to
Exton, PA
Began Phase I
Clinical
Operations
2006
2012
March 2015 Acquired BDM
with Data
Management
and Biostats
Services
Strategic Investment
Agreement with
Tigermed
2015
2015
June 2015 Opened new
clinical site in
Secaucus, NJ
Sister CDMO
company
Frontida
acquired in
Philadelphia, PA
2016
Staff number grew from 1 to 500+
2
Locations around the globe
160-Bed Facility
• Early Phase Clinical
•
USA
Headquarters
Bioanalytical, DMPK
•
Exton, PA
CMC Services
•
Exton, PA
Secaucus, NJ
CHINA
•
Bioanalytical Services
•
Data Management
and Biometrics
• BDM Consulting
Shanghai, Suzhou
CMC Services
•
Somerset, NJ
Suzhou
Hospital-Based Clinical Units
1) 48 beds Frontage TICH
Clinical Research Center,
Tianjin
2) 78 beds at Jilin University
in Changchun
3) 60 beds at Hainan site
4) 36 beds at Nanjing site
5) 36 beds at Jinan site
6) Another 4 sites with over
200 beds established by
the end of 2016
3
Service Offerings
Laboratory Services
Clinical Services
DMPK
BIOANALYTICAL
CMC
CLINICAL
BIOMETRICS
Insight.
Expertise.
Quality.
Agility.
Intelligence.
It’s how your candidates
become real contenders.
It’s how you get from the
molecule to the market.
It’s how you get from
formulation to the pharmacy.
It’s what gets you from the
clinic to the cabinet.
It’s how you turn data
into decisions.
• Rapid PK; In Vitro
ADME
• Mass Balance
• Early Discovery to Late
Development
• Metabolite
Identification
• Biomarker Services
• Preclinical and Clinical
Support
• Global Bioanalytical
Services (50+ LC-MS/MS)
• Biologics Assay (Antibody
Drug, ADC,
Oligonucleotide)
•
•
•
•
• Multiple Clinical Centers
in US and China
• Phase I, SAD, MAD
• First to File Packages
• BA/BE, Food Effect, DDI
• CDISC-Compliant Datasets
• SAS Programming
• Preclinical-Phase IV
Development Support
• EDC & Data Management
Analytical
API Synthesis
CTM Manufacturing
Formulation Development
4
US FDA Facility Inspections (2004-2016)
Service Area (Location)
FEI #
# Facility
Inspection/s
Inspection Year/s
BIO-US/ CMC-US (HQ, Exton, PA)
3003542039
10/2
2004-2016
CMC-US (Exton, PA)
3006799640
7
2006-2016
CRC-US (Hackensack, NJ)
3005134380
4
2009-2014
CRC-US (Secaucus, NJ)
3011480129
1
2016
BIO-CH/ CMC-CH (CH HQ, Shanghai, China)
3006272169
2/1
2013
CRC-CH (Zhengzhou, China)
3007302943
1
2013
CRC-CH (Changchun, China)
3011212396
1
2015
CMC-CH (Suzhou, China)
3011329032
1
2016
30
2004-2016
Total US FDA Facility Inspections
v. Oct2016
5
Other Regulatory Inspections (2009-2016)
Service Area (Location)
Agency
# of Inspection/s
Inspection Year/s
BIO-DMPK-US (HQ Exton, PA)
US EPA
1
2015
CMC-US (Exton, PA)
Health Canada
1
2016
Clinical Investigator (CI) - US/China
US FDA
4
2009-2015
BIO-CH (Shanghai, China)
WHO
1
2013
CRO-CH (Beijing, China)
WHO
1
2013
CRC-CH (Zhengzhou, China)
WHO
1
2013
v. Oct2016
6
Why Frontage?
Technical Expertise
Highest Standards
Flexibility
Innovation
With 70% of our scientists
holding advanced degrees
and our depth & breadth
of experience, we can
solve complex problems
We have an
unparalleled
compliance and
quality track record
with 29 FDA
Inspections across GXP
We value agile project
management, &
a commitment to
completing projects on
time and on budget
Our $40M facility
investment and 450 FTE
in USA & China give us
the latest equipment
and unparalleled access
to China
7
Laboratory Services
DMPK
8
Drug Discovery & Development
Hits to Leads
Lead
Optimization
Pre-clinical
Registration
(IND) Phase I
Phase II
Phase III
Commercial
Launch (NDA)
Phase IV
DMPK Services – from Discovery to NDA
Discovery Studies
• PK/PD Studies
• PK Screening
• In vitro Studies
• Structure Optimization
Preclinical Studies
• Metabolite ID/Profiling
in different species
• In vitro ADME studies
for IND/NDA
Clinical Studies
• MIST
• Drug-Drug Interaction
Studies
•
14C-ADME
Studies
9
DMPK Overview
One-stop Shop
Experienced Staff
• Iin vitro/in vivo DMPK
support for discovery
and development
• EPA, GLP, & non-GLP
studies; QA support for
regulated studies
• Vivarium – AAALAC
certified
• 25+ employees; crosstrained; avg.
experience 10-15 years
• Ability to provide
scientific input to
designs and
interpretation of data
to influence decisionmaking process
Varied Client Base
•
•
•
•
•
Pharmaceuticals
Universities
NIH
Government agencies
Agro-chemical
companies
10
Laboratory Services
Bioanalytical
11
Global Bioanalytical Operations
• ~ 130 Staff in USA
and China
• 80,000+ Sq. Ft.
• Majority of Scientists
Hold Advanced Degrees
Team &
Facilities
• 1,400+ Mostly
Proprietary Assays
• 500,000+ Samples
(Annual Capacity)
• Mostly Proprietary
Assays
• 200,000+ Samples
(Annual Capacity)
• 80+ Available Assays
• Ongoing Customized
Assays and Therapeutic
Focus
• 58 LC-MS/MS
Small
Molecule
Biologics
Biomarker
12
Small Molecule Capabilities
Method Development,
Transfer & Validation
Sample Analysis
• Nonclinical
toxicokinetic/pharmac
okinetic screening
• Clinical
PK/bioavailability
studies
• Bioequivalence studies
• Therapeutic drug
monitoring studies
• Drug-drug interaction
studies
• Protein binding studies
Expertise in New Sample
Collection Procedure
Development
• DBS sampling
• Micro-sampling
techniques
• Analyte stabilization
procedures
Expertise in Labile
Compound Method
Development
• Enzymatic instability
• Physical/chemical
instability
13
Biologics Capabilities
Molecule Types
Analysis Method
Biologics
Monoclonal Antibodies, Antibody Drug Conjugates, Oligonucleotides, Peptides, Biomarkers
Ligand Binding Assays
ELISA & ECL
LC-MS/MS
PK/TK – Pharmacokinetics Assays
Immunogenicity Assays
Techniques
Anti-Drug Antibody Assays, Neutralizing Antibody
Assays, Characterization Assays
Cell Based Assays
Functional in vitro assays, Toxicity & Viability
14
Laboratory Services
CMC
15
CMC Teams
Organic Synthesis API
Product Development
Analytical Testing
CTM Manufacturing
16
Product Development and CTM Manufacturing
Work with > 170 clients for > 170 compounds and
>370 GMP batches
IND: Formulation
Development /CTM/IND
(OSD, Topical, Sterile)
High Potency Suite for
CTM Manufacturing
ANDA: Reverse
Engineering/Formulation
Dev/Tech Transfer
•Formulation and Process
Development (QbD format)
Sterile Suite for CTM
Manufacturing (Phase 1)
Proof of Concept Studies
in Animals via Frontage
and 3rd Party Facilities
Consumer Products: OTC
reformulation
DEA Manufacturing
License for Controlled
Substance (CI-V)
Integrated Services with
Frontage Clinical Center
17
Analytical Services
Method Development, Validation and Transfer
•Developed and/or validated over 1,350 methods (~100 methods/year)
•HPLC (20), UPLC (22), GC (2), GC/MS, IC, HPLC/MS, UPLC/MS, ICP/OES, ICP/MS
•Dissolution (16)
•Diffusion IVRT and Skin Permeation IVPT testing (48 Franz cells)
Unknown Impurity Identifications
•Fraction collection, lyophilization, LC-MS-MS, NMR
Extractable/Leachable Studies
•GC/MS, LC/MS, ICP-OES or MS
API and Finished Product Release Testing
Commercial Product Stability Testing and Storage
GLP Dosing Sample Analysis
DEA License for Testing Controlled Substances Schedule I-V
18
GMP Sample Stability Testing
FDA-Inspected Labs for commercial stability study
Over 4,500 cubic feet of storage (6 walk-in 8’x8’ rooms; 6 reach-in
chambers)
Typical ICH storage conditions & WHO (Zone IVb hot/higher humidity)
•25oC/60%RH, 30oC/65%RH, 40oC/75%RH, 30oC/75%RH
Low Humidity for Semi Permeable Containers (Ophthalmic Products)
•5oC, 25oC/40%RH, 40oC/25%RH
Low Temperature for Parenteral & Lyophilized Products
•-70oC, -20oC, 5oC, 25oC/60%RH
ICH compliant photo-stability chamber
24/7 e-monitoring system/Emergency back-up power generator for
continuous operations
19
Clinical Services
Clinical
20
Clinical Research Facility – Secaucus, NJ
• State of the Art Facility
• Less than 5 miles from NYC
• ½ mile from local medical center
• Near major airports and mass transit
• 36,000 sq. ft.
160 Beds
• Multiple units can be combined to
accommodate any size study
• Telemetry Unit
• Safe drug handling including
controlled substance management
(Schedule 2-5 license)
21
Clinical Research at A Glance
Seven Early Phase
Clinical Facilities in the
U.S. and China
Data Management and
Biometrics
EDC support & statistical
programming, including eSubmission and CDISC
support
Experience with novel
compounds and
access to a diverse range of
subject populations and
patients
Clinical Study Design
and Execution
Medical Writing and
Regulatory Support
Early phase focus,
monitoring and study
management for multicenter studies (PK/PD)
Clinical protocol
development, Investigator’s
brochures, CSR
22
Diverse Study Experience
Study Types
Over 20 years of experience in conducting
early phase clinical trials
Studies Completed in Last 6 Years
Total - 226
Dosage & Delivery Forms
24, 11%
17, 7%
PK/PD
80, 35%
DDI
22, 10%
FIH
BE
PoC
PK
18, 8%
65, 29%
• First-in-Human
• Single and Multiple Dose Escalation
• Bioequivalence
• Absolute and Relative Bioavailability
• Drug-drug Interaction Studies
• Food and Alcohol Effect
• Topical
• Oral
• Injectable
• Inhalation (MDI)
• Intranasal
Therapeutic Area’s
• Cardiovascular
• CNS
• Dermatology
• Gastrointestinal
• Infections
• Inflammation
• Men's’ and Woman’s Health
• Pain Management
23
Clinical Services
Biometrics
24
Biometrics Services to Rapidly Compile the Clinical
Study Report
Data Management
• Rigorous SOPs
for Regulatory
Standards
Adherence
• Optimized DM
Solutions - Pair
Technology to
Study
• Reliable, HighQuality Delivery
Supported by
Experienced
Teams
Biostatistics and
Programming
• Biostatistics
Consultation
and Analyses by
Staff statisticians
with more than
20 years of
industry
experience
• Statistical
Programming
Medical Writing
Regulatory
• Pharmacokinetic
(PK) Analysis led
by PhD Clinical
Pharmacologist
with 25 years of
experience
• Insight into
Clinical
Development
Plans, Study
Designs and the
Regulatory
• Medical Writing
from to Clinical
study reports
• Approval Path
Led by former
FDA reviewer
25
Snapshot of China Operations
Clinical
CMC
Bioanalytical
26
Frontage China Operations
Headquartered in
Zhangjiang Hi-Tech Park,
Shanghai
Labs in function from
2006 (the first global
standard GLP lab in China)
Director and above levels
are trained abroad and
have multiple years
working experience in
Pharmaceutical industries
Multiple times
successfully passed FDA
and WHO site inspections
(GLP/GMP/GCP)
27
Frontage China Services
Bioanalytical
•
•
•
•
•
>26,000 sqf facilities
located in Shanghai and
Suzhou
>50 Scientists; >70%
have advanced degrees
Clinical
CMC/CTM
•
>30,000 sqf facilities
located in Suzhou
•
•
16 LC/MS/MS with
WatsonLIMS system
US-China method cross
transfer and validation
abilities
•
Support sample analysis
for small molecules
drugs and biologics
•
•
>40 Scientists; >70%
have advanced degrees
Hospital-based early
phase clinical centers in
different regions
•
Analytical method
dev/val; stability and
release testing
>250 beds phase I
capacity currently;
about 600 beds mi 2017
•
Various therapeutic
area experience
•
DM/BioStat fully
support functions
•
Late phase clinical trial
capabilities
Formulation
development – various
dosage forms
Clinical trial material
manufacturing
28
Global Headquarter Locations
U.S. Headquarters
China Headquarters
29