Post on 13-Mar-2020
Presentation overview
Clinigene Overview
Clinical Pharmacology Studies
Clinical Trial Management
Clinical Data Management Services Medical Writing & Pharmacovigilance Services
Laboratory Services
Organization overview
Clinigene is a fully-owned subsidiary of Syngene, a discovery & development solutions provider for Pharmaceuticals and Biologics
Syngene & Clinigene together form India’s largest CRO group with a staff of 2000 scientists and with a client base of over 120 global pharma & biotech companies
DISCOVERY & DEVELOPMENT
Medicinal Chemistry
Discovery Biology
DMPK & Assay Biology
In vivo pharmacology
Toxicology (GLP/ non-GLP)
Custom Synthesis
Process R&D/ cGMP mfg
Biologics Development
Formulation Development
Clinical Supply Manufacturing
Analytical & Stability Studies
Regulatory Support
Polymer Chemistry
CLINICAL RESEARCH
Early Phase Clinical Dev.
Bioanalytical Research Lab
Central Laboratory
Late Phase Clinical Research
Integrated eClinical Services
Clinical Data Management
Regulatory Affairs
Medical Monitoring
Safety Management
Medical Writing
Immunogenicity Testing
Pharmacovigilance
Clinigene Services
Oncology
Diabetology
Rheumatology
Metabolic disorders
Dermatology
Cardiovascular
Gastroenterology
Nephrology
Immunology
Infectious Diseases
Neuropsychiatry
Small Molecules
Biologics
Biosimilars
Vaccines
Devices
Neonatal
Pediatric
Adult
Healthy volunteers
Specific patient population
Therapeutic Areas
Products Study Populations
EDC, Data Mgmt. & Biostatistics
Regulatory Affairs & Pharmacovigilance
Medical Monitoring & Safety Management
Medical Writing
Bioanalytical & Immunoassay services
Human Pharmacology Studies
Clinical Trial Management
Quality Assurance
Central Laboratory Services
Clinical Research Experience: Operations
No. of Patients (Phase I-IV)
Therapeutic Area-wise (Phase I-IV) Phase-wise
0
10
20
30
40
Diabetology Oncology Bone &
MetabolicDisorders
Others
26
13 1116
0
1000
2000
3000
Diabetology Oncology Bone &
MetabolicDisorders
Others
2400
910
1700
990
0
50
100
150
200
BA/BE Phase I Phase II Phase III Phase IV
170
1425 27
2
Employee profile
Highly skilled workforce of 170 employees with 74% having advanced degrees
7% 7%
60%
26%
MD
PhD
Masters
Graduates
Presentation overview
Clinigene Overview
Clinical Pharmacology Studies
Clinical Trial Management
Clinical Data Management Services Medical Writing & Pharmacovigilance Services
Laboratory Services
Human Pharmacology Unit - HPU
State-of the-art, DCGI approved facility with 84 beds & 8 ICU beds
Managed by team of 25 researchers, including 4 physicians, conducting
o BA/BE studies
o Early phase studies (In-house & off site) incl. FIH, SAD, MAD, DDI and Patient studies
Experience conducting PK studies on various dosage forms: Tablets, capsules, ER, nasal formulations, topicals and parenterals
Database of healthy male (90%) & female volunteers (10%): 5000+
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Human Pharmacology Unit (HPU): Infrastructure
About 22,500 sq ft facility
Dedicated area for all activities: Counseling, Housing, Recreation,
Dining, Sampling, Sample processing, Pharmacy
Separate housing facility for female volunteers
ICU equipped with telemetry, defibrillator, ECG machine, infusion
pumps, glucose analyzer
24/7 ambulance & contract with a tertiary care hospital for
emergencies
Comprehensive set of SOPs and IOPs
HPU: Regulatory Credentials
Studies submitted to US-FDA, EMA, TPD [Health Canada], MHRA and DCGI
HPU & Bioanalytical lab were inspected by
AGES/EMA (Sep’10): Study specific Audit (2 BE studies inspected) - no major findings
US-FDA (Jan’11 and Feb’12): Study specific Audits (5 BE studies inspected overall) – no 483’s
ANVISA -Brazil (Jan’12): Systems Audit – no observations, Facility certified for conducting BA/BE studies
AEMPS/EMA (Jan’13): Study specific Audit (one BE study inspected) - no major findings; Clinigene rated as Top 10 for EMA
GLP Audit by Thai FDA (Feb’13): Study Specific Audit - no major findings
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Phase-1 center for studies in special populations
Inaugurating a state-of-the art 16-bed Phase 1 patient unit at Mazumdar-Shaw Cancer Center in Bangalore
o ICU-like setting for intense Phase 1 studies in oncology, cardiology, immunology and respiratory diseases
o Part of Narayana Hrudayalaya Health city (more than 2500 beds in same campus)
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Phase 1 studies:
o Dose escalation studies on insulin formulations
o Comparative bioavailability study with inhalation insulin
o Food interaction study with Oral insulin
o Phase IIa study of anti-CD34 Mab
o PK-PD studies on Novel transdermal gel and patch for NSAID
o Drug-Drug Interaction Studies
BA/BE studies to support ANDA and 505(b)2 applications
Phase I Experience
Presentation overview
Clinigene Overview
Clinical Pharmacology Studies
Clinical Trial Management
Clinical Data Management Services Medical Writing & Pharmacovigilance Services
Laboratory Services
Capabilities in Patient-based studies
46-member strong Clinical Operations & Regulatory Affairs team
Have a good mix of experienced staff with prior experience in multinational CROs and Big Pharma
Strong therapeutic experience in Oncology, Diabetes and auto-immune disorders
Advantages offered:
India Advantage: faster patient recruitment, up to 40% cost savings relative to US or Europe
“One stop shop” solution: Regulatory support, Trial management, IP management, Central Lab and Data Management
Strong project management systems & Long track record of working with several overseas clients
Investigator Database – CliniBase®
Therapeutic Area No. of Investigators Worked with Clinigene
Oncology 157 44
Endocrinology 134 57
Cardiology 77 10
Neurology 43 4
Dermatology 61 21
Gastroenterology 54 19
Rheumatology 10 10
Orthopedics 21 5
Nephrology 32 7
Pediatrics 23 8
Clinigene has worked with more than 190 Investigators
Project based relationship with Investigators, SMOs, Hospitals & Institutes
Bangalore
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Clinical trial capabilities in Patients: Site network
17
Synopsis receipt & review by
internal departments
Discuss & finalized synopsis with
Sponsor
Exchange of responsibility matrix
Feasibility assessment
Finalization of Budget &
milestone payment
Signing of the MSA or LoI
Handover meeting
Site selection
Study team set-up & training
Regulatory and EC submissions
Investigator meeting
Receipt of study supplies at
Clinigene
Site initiations
Patient recruitment
Site monitoring (clinical,
safety, drug a/c, DM queries)
Co-ordinate & track
Investigator payments
Regular meetings on study
progress & MoMs
Use RACI to identify issue
escalation path and teams
Sponsor /customer feedback
mechanism
Data queries and resolution
process
Data base lock
Site close-out activities
Discussions and approval of
Statistical analysis report
CSR writing
Study supplies return and/or
destruction
Archiving study documents
(Post Study)
Study
Set-up
Study
Conduct
Study
Closure
Clinical Operations-Project Management
Presentation overview
Clinigene Overview
Clinical Pharmacology Studies
Clinical Trial Management
Clinical Data Management Services Medical Writing & Pharmacovigilance Services
Laboratory Services
Capabilities in Laboratory Services
One of the most experienced central labs in India solely focused on
supporting clinical research
Apart of routine clinical chemistry, we have extensive experience in
providing biomarker services using IHC, Flow cytometry and ELISA/MSD
platforms
Strong track record in providing GLP-compliant PK services for small
molecules and large molecules, and immunogenecity and cell based assays.
Small molecule BA lab was inspected by FDA, EMA and ANVISA. Both
bioanalytical labs are expected to receive GLP certification by Q1 2013
Central Laboratory: Overview
Offers clinical testing services exclusively for Phase I-IV clinical trials and BA/BE studies
Certifications and Accreditations:
College of American Pathologists (Since 2002)
NABL (ISO15189)
NGSP Level II for HbA1c
21CFR-11 compliant Laboratory information management system with customizable project management and reporting capabilities
Intercontinental referral lab for LabCorp Clinical Trials, Belgium, a LabCorp company, USA.
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Services
Project Management
Analyte Testing
Kit building
Sample Storage & Management
Identification and outsourcing to specialty laboratories globally
Data management
21
Services offered as Full service study package / stand
alone service
Training - Investigator sites and study teams
Assay Development & Validation
Consultancy services
Value-added services
Optimize sample collections for your protocol
Select the correct test methods to suit your protocol
Talk to our subject experts to resolve your queries
Understand the quality requirements for success
Get insights into “Indian population data” for tests
Review potential pre-analytical and analytical issues before the onset of the study
Access to laboratories and experts across the globe to help resolve protocol related issues
How you can benefit from our expertise
Your Project
Project Manager
Project Monitor(s)
Kits & Logistics Coordinator
Technical team
Data Manager
Dedicated study management
teams
Central Lab Services- Analytical Solutions
Biochemistry
Coagulation studies
Endocrinology
Hematology
Serology
Inflammatory/ immune markers
Virus antigen detection
Histopathology
Immunohistochemistry
Flow cytometry
DNA extraction and storage
CAP and ISO15189 compliant quality systems
Globally harmonized testing platforms and procedures
Experience with global studies, sponsors and regulators
Bidirectional interfacing- Minimal manual intervention
Large capacity to scale up
Experience in setting up unique biomarker assays
Validated & optimized reference ranges for Indian population
Testing/Analytical Services
Key Advantages
Biomarker Experience:
Immunohistochemistry {tissue blocks}
EGFR, p-EGFR, ErbB2, ErbB4, pAkt, p-MAPK, p-STAT3, c-Myc, Cyl D1,
TGF-α, PCNA, VEGFR, PECAM-1, p-EGFR, and mTOR,CD3,CD20
Flow cytometry
Multicolor lymphocyte Immunophenotyping assays for phase III
studies- CD3, CD4, CD8, CD45RA, CD45RO, CD19, CD56
CD34+ Hematopoietic stem cell enumeration (PD marker)
B cell depletion assays (CD19 and CD20)
Multiplex assays ( over 4 different cytokines in a single 25µL sample)
Access to Intercontinental Labs
Experience with Labcorp Clinical Trials
Service Level Agreements since 2006
Over 6 years of working experience
Over 51 global projects completed
Harmonized processes and platforms
Inter-laboratory correlation data
Performed 2 studies across the globe from Clinigene
Access to specialty laboratories for pharmacogenomics, coagulation, viral genotyping and drug resistance assays
Partnership with Pacific Biomarkers in 2011
Biomarker services offered in collaboration with Pacific Biomarkers
Diagnostic product development
Novel biomarker assay development
Cell based assays
Multiplexing capability
Scientific consultation
Protocol design
PBI
Drug
Development
Diagnostic
Development
Technology
Transfer & Assay
Development
22 years of combined
experience in Rx and Dx
development:
Domain Expertise in Large, synergistic Therapeutic Areas
Lipids &
Cholesterol
Metabolic
Syndrome &
Obesity
Diabetes
Acute Organ
Injury
CV
Diseases
Bone,
Inflammation
& Immunity
HDL
Functionality
Pacific Biomarkers- Expertise
Bioanalytical Laboratory (Small Molecules)
Successfully audited by US-FDA, EMA, ANVISA
Operational since May 2004, spreads over 7500 sq. ft.
State-of-the-art instrumentation [with qualification]
Team of qualified and experienced researchers with experience in method development, validation and regulated bioanalysis for a wide range of chemically diverse drug molecules
Analysis of drug/s and/or metabolite/s in biological specimen [e.g. blood, plasma, serum etc.] to support PK, early phase clinical development, BA/BE and TDM studies
Processes meeting applicable GLP requirements
Method validation as per USFDA guidelines
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Infrastructure
LC-MS/MS
LC-MS/MS ( API 4000 and API 4000 Q-TRAP): 6
Agilent 1100 series - API 4000 : 2
Shimadzu SILHTc - API 4000 : 1
Shimadzu SILHTc - API 4000 Qtrap : 1
Shimadzu –SIL 30ACMP : API 4000 : 1
Analyst ® 1.4.2 and 1.6.1 [21CFR Part 11]
Laboratory Information Management System (LIMS)
WatsonTM – ThermoFisher
Sample Processing
TurboVap ®Sample concentrator
Ezypress ® 48 SPE sample processor
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Experience with Novel Biologics, Biosimilars, Fusion Proteins/Peptides
Immunoassays/Ligand Binding assays
OECD GLP and GCLP Compliant
Support in early and late phase Drug Development
(Pre)/Non-Clinical & Clinical Studies: All biological matrices
Potency, Pharmacokinetics & Immunogenicity (Antigen –Antibody Reactions)
Method Development/Transfer, Validation & Sample Analysis
LIMS integrated data management
On-site Sample Accession and Management Team
Bioanalytical Laboratory (Large Molecules): Overview
Immunogenecity Services
Screening Assays
Confirmatory assays
Confirmatory Titre
Neutralizing Ab
Isotyping
Methodology
Technology Platforms
RIPA
Cell Based Assays
Biacore
ELISA
Method Feasibility/ Transfer/
Development
Method Validation
Sample Analysis Report Writing
ECLIA
Method Feasibility & Devlopment/
Transfer
Method Validation
Sample Analysis Report Writing
RIPA
CLIA
Insulin's & Insulin Analogues
ECLIA
ELISA
Cell Based Assays
M-Ab’s & Other Biologics
Biologics & Bio-similars
Pharmacokinetics/Toxicokinetics Services
Ligand Binding Characterization
Biacore
Interactions between • Receptor-Ligand • Drug- Receptor • Antigen-Antibody • Drug-Antibody • Nucleic acids- Proteins • Nucleic acid- Nucleic acid • Protein-Protein
Specificity
Concentration
Kinetics
Affinity
Targets
Technology/Solution
Method Feasibility & Devlopment/
Transfer
Method Validation
Sample Analysis Report Writing
Drug/ Therapeutic Area Laboratory Evaluation
Insulin/Insulin Analogues, recombinant
growth factors, hormones, hormone
analogues, recombinant proteins
Immunogenicity
Pharmacokinetics/Toxicokinetics
Potency/efficacy
Receptor binding characterization
Monoclonal Antibodies Immunogenicity
Pharmacokinetics/Toxicokinetics
MAb-target interaction
Anti HCP (host cell protein) Immunogenicity
Recombinant enzymes for therapy Pharmacokinetics/Toxicokinetics
Immunogenicity
Metabolic disorders Metabolite efflux assays
Testing - Expertise
Presentation overview
Clinigene Overview
Clinical Pharmacology Studies
Clinical Trial Management
Clinical Data Management Services Medical Writing & Pharmacovigilance Services
Laboratory Services
Clinical Data Management
Case Report Form (CRF) Design
Workflow Management
Data Capture
o Double data Entry
o Electronic data capture
Query Management
Discrepancy Management
Medical Coding
o Adverse Event & Medical History
o Concomitant Medications
Serious Adverse Event Reconciliation
Data Management Plan
Data Entry & Validation guidelines
Study Setup
CRF Tracking
Data Capture/Testing
Data Validation
QA/QC (Acceptable limit of 0.05% error rate)
Database Lock
Data Transfer (Secured FTP access for Lab data transfer)
Process Elements
Services
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Biostatistics
Statistical inputs for protocol
design
Sample Size Calculation
Randomization/Blinding
SAS Coding
Statistical Analysis
Statistical Report
Statistical Analysis Plan
Report Analysis Plan
o Tables, Listings and Graphs
Statistical Analysis
Validation of SAS Code and
Statistical Analysis
Statistical Report
Services Process
Elements
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Software Tools
SAS PheedIt V 3.00.016 – Clinical Data Management (EDC/Paper) A 21 CFR Part 11 Compliant system from SAS, capable of importing data from different formats (ASCII, Excel, CSV, SAS etc.)
SAS Analytics V 9.3 – Statistical Analysis
MedDRA V 15.1 – Adverse Event / Medical History Coding
WHO-DDE – Medication Coding
Adobe Pagemaker V 7.0 – CRF Designing
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Experience
Therapeutic Area No. of
Studies
Endocrinology 11
Oncology 7
Immunology 5
Dermatology 1
Hematology 1
Rheumatology 1
Phase No. of Studies
BA/BE 64
Phase I 1
Phase II 8
Phase III 14
Phase IV 3
Presentation overview
Clinigene Overview
Clinical Pharmacology Studies
Clinical Trial Management
Clinical Data Management Services Medical Writing & Pharmacovigilance Services
Laboratory Services
Medical Writing - Group
A 5-member team of skilled medical writers with scientific expertise to support clinical development
Have a good mix of experienced staff with prior experience in multinational CROs and Big Pharma
Collaborates with our Statisticians and project coordinators in constructing submission-ready clinical documents.
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Role Qualification No. of
people
Experience
in yrs
Principal Medical Writer MBBS, MD 1 12 yrs
Associate Medical Writer MBBS, MD 2 5 yrs
Assistant Medical Writer MBBS 1 8 yrs
Assistant Medical Writer M.Sc (Life sciences) 1 3 yrs
Medical Writing Services
• Regulatory Documents for Phase I to IV Studies
– Investigators brochure
– Clinical study protocols
– Informed consent forms
– Study assessment questionnaires
– Patient dairies
– Clinical study reports DSMB Charters
• Clinical study reports – Observational studies
• Abstracts and Journal manuscripts
• Poster presentations at medical meetings
• Clinical overview and clinical summary
• Training materials
42
Services offered as Full service study package or stand alone service
All of the above listed documents undergo QC and QA review.
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We provide global pharmacovigilance services, including:
• Adverse Events’ Case Processing: data collection, processing, medical review, safety writing, reporting, signal detection and analysis.
• Aggregate Report Writing
• Drug Safety reporting to Indian regulatory agency (DCGI)
Salient features of our Pharmacovigilance group:
• Team Composition: Derived from best-in-class IT & Pharma companies.
• Strong Project Management Systems
• Trainer: Training personnel for new and ongoing training
• Service Management: SLAs tracked by the service management team.
• Best Practices: Case processors trained in best Pharmacovigilance practices.
Pharmacovigilance Services
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Pharmacovigilance Services
Phase-1/ BE studies Phase – II and III trials
Centralized Inbound Unit for AEs & SAEs
Case Triage &
Processing
Medical Review &
Causality
Assessment
Case Submission
Safety Signal evaluation
Periodic Reports (IND AR, NDA PR,ASR)
Integrated Summary of Safety
Design Risk Management Strategy
Case Processing and
submission*
Literature Search &
Review
Risk Management Plans
(RMP,REMS, RiskMAPs)
Annual & Ad-hoc safety
signal evaluations
Periodic Reports
(PSURs, PADERs,
Bridging Reports, Ad-hoc
Reports)
Establishing and
operating special
population registries
Clinical Development Post- Approval
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PV services: Why Clinigene?
• Personnel well-trained & experienced in the current safety reporting guidelines (ICH E2A & E2C, CIOMS guidelines, US FDA's Good Pharmacovigilance Practices &EMEA's European Directive 2001/20/EC guidelines etc.)
• Customised offerings as per end-user requirements & client specified Service Level Agreements (SLAs)
• Database-independent: Flexibility, knowledge & experience to work on sponsor’s proprietary or licensed electronic reporting databases such as Argus Safety, Aris-G, Clintrace, etc.
• Location: In Bangalore, India’s IT Hub with good internet connectivity, and ample availability of experienced personnel
• IT Support: Good infrastructure manned by in-house IT group
• BCP: Alternate locations for service outages