comprehensive clinical development solutions...human pharmacology unit - hpu state-of the-art, dcgi...

Comprehensive C l in ica l Development Solut ions

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


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


Clinigene Overview




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+

8

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

10

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


Clinigene Overview




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

16

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


Clinigene Overview




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

28

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


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


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


Clinigene Overview




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

37

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


Validation of SAS Code and


Statistical Report

Services Process

Elements

38

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


Clinigene Overview




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.

41

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.

43

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

44

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

Clinigene’s Facility

Thank You!