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LAMBDA THERAPEUTIC RESEARCH Delivering total drug development solutions
“The best companies outsource to win, not to shrink. They outsource to innovate faster…” - Thomas L. Friedman
GLOBAL PRESENCE
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Warsaw, Poland 2007
London, UK 2008
Toronto, Canada 2010
Istanbul, Turkey 2011
Bangkok, Thailand 2011
Ahmedabad, India 1999
Mumbai, India 2003
New Delhi, India 2009
Hyderabad, India 2009
COMPREHENSIVE SOLUTIONS
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phase I/BA-BE PHASE II PHASE III PHASE IV (PMS) Pharmacovigilance
EXPERIENCE MEDICAL IMAGING E-SUPPORT SERVICES
REGULATORY INSPECTIONS
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EMA [01]
CDSCO [12]
US-FDA [30]
CAP [06] WHO [03]
UK-MHRA [04]
Thai MOH [03]
OGYI [01]
ANVISA [07]
ANSM [02]
HEALTH CANADA [01]
PHSS [01]
TURKEY MOH [01]
AGES [01]
POLISH [01]
TIME EFFICIENCIES-ACTUALLY RESEARCH ACCELERATED…
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Lambda
Company X
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LAMBDA
SERVICES
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In-house facility of 600+ beds in clinic, including 36 Phase-I and 12 ICU beds
Sr. No
Country City No. of Beds Phase I Beds ICU Beds
1 India Ahmedabad 360 16 8
Mumbai 65 - 2
2 Canada Toronto 122 12 -
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GLOBAL CLINICAL BED FACILITY & VOLUNTEER DATABASE
Global database of over 150K volunteers comprising of healthy male, female and geriatric
Population Ahmedabad Mumbai Toronto
Healthy Male 31781 8050 60,000
Healthy Female with childbearing potential 1985 300 30,000
PM & Surgically Sterile Women 1775 150 2,200
Elderly 620 50 3,500
Software – Biometric method for volunteer identification, BizNET for clinical operation
UNIQUE FEATURES
• Conducted 5000+ BA/BE Studies
• Having major experience with 20+ TC’s viz. CVS, CNS, GI, Musculo-skeletal,
Endocrinology, Dermatology and others
• Have worked with 150+ domestic and international sponsors
• 21 CFR compliant paperless solution (BizNET) for data capture of early phase
clinical trials – we are the pioneers
• Regulatory inspections: No critical observations till date
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PHASE-I
Infrastructure
• Dedicated state-of-the-art ICU’s
• Central Cardiac Monitoring System
• Cardiac Telemetry/ Holters / IV Infusion Pumps
• X-ray, Ultrasound facilities
• TQT studies
• GE MUSE system for ECG processing and management
• GE Apex Pro Telemetry System / DASH 4000 Cardiac Monitors
• Multilevel ECG reading
• Internet access to ECG data through ECG web portal
Study offerings • SAD – MAD studies • PK / PD Studies • Drug – Drug Interaction • Drug – Food interactions
DDI
12%
First in
Man
38% Food-Drug
interaction
12%
SAD
20%
MAD
18%
Live attenuated H1N1 influenza vaccine, 1
Inactivated H1N1 influenza vaccine, 1
Anti Asthmatic drug, 1
Anti Infective agent, 6
Lipid Lowering agent, 3
Alzheimer’s disease, 6
Multiple Sclerosis, 1
Anti Hypertensive agent, 3
Anti diabetic drug, 2
Antifungal drug, 1
Hormonal agent, 1
Immunosuppressant, 1
Anti cancer( receptor modulator), 1
Anti obesity drug for Metabolic syndrome, 1
NCEs, 5
TC EXPERIENCE
• Largest GLP certified bioanalytical lab. with over 14 & 25 years of experience in Asia and North America respectively.
• Experience of analyzing > 3 million samples at India facility and > 3.5 million samples at Canada facility
• > 700 validated assays in different matrices (plasma, whole blood, serum, urine, CSF, bone, fecal, milk and food)
• Capabilities to handle analysis of pre-clinical studies
• Average of > 8 years experience for the analysts, reviewers and scientists
• > 5 validated methods with LLOQ of ≤ 2 pg/mL
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BIO ANALYTICAL EXPERIENCE
• Rapid TAT for FTF opportunities
• Proactive identification & method development for FTF opportunities/molecules
• Two layer 100% data review process
• Synergy of systems and processes through global SOPs between locations
• Methods available for NCE molecules in CSF using as low as 25 µL aliquot volume
• Readily available methods for current critical & FTF opportunity molecules
Fingolimod & Fingolimod Phosphate, Free & Total Dabigatran, Dronedarone, Prasugrel
• Methods available for Biomarkers like Prostaglandin metabolites 6-Keto PG1α, TxB2 and T-pgem
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BIO ANALYTICAL USP
• Advantage of strategic locations (India & Canada) for servicing clients globally
• 30+ successful bioanalytical regulatory inspections with no critical observations
• Bioanalytical experience of measuring drug and metabolite for > 5000 studies
• Ability to analyze > 85K samples in India and >15K samples at Canada in a month
• Average reanalysis: 3-5 % of total samples
• > 95% of ISR samples met the acceptance criteria
• In-house, experienced team of engineers to ensure >95% uptime of instruments
• Capacity to store >3.5 million samples in India and > 1.5 million samples in freezers at Canada
• Global method validation and run acceptance SOP complying requirements of all regulatory bodies
• Canada facility approved for handling controlled substances
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BIO ANALYTICAL STRENGTHS
CLINICAL DATA MANAGEMENT SYSTEM
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BIZNET
Investigative Site Clinical Data
Management Biostatistics &
Reporting
Software Version Activity
BizNET® (CTM & BA/BE) 4.0 EDC / eCRF
MedDRA® 17.0 Medical Coding
SAS® Server 9.3 Statistical Software
Phoenix® / WinNonlin® 6.3 / 5.3 Pharmacokinetic Analysis
CDM & BIOSTATISTICS SERVICES
• CRF / eCRF designing
• CRF annotation as per CDISC
• Data Management Plan
• Database designing and UAT with dummy data
• Data validation & Query resolution
• External data upload & cleaning
• TMF management
• EDC Training for the site personals
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BizNet BENEFITS • Cost Effective (~ 60%) • Locally available System Support
• Sample size and Study Design
• Protocol inputs / review, SAP & mock shells
• Statistical analysis & reporting
• Customized tables, graphs, and data listings
• Statistical interpretation of study results
• BA/BE Studies in multiple groups
• Scaled approach & replicate design
• Two stage design
• Pharmacokinetic & PD parameters
CDM BIOSTATISTICS
EXPERTISE IN SPECIAL TYPE OF DATA ANALYSIS
• In vitro data analysis for Equilibrium Binding & Kinetic Binding (e.g. Sevelamer, Colesevelam)
• Statistical testing for data on Particle size analysis (e.g. Azacytidine Inj.)
• Two-stage study design (Adaptive study / Group Sequential approach)
• Data Analysis based on latest OGD requirements like Scaling approach for NTI drug (e.g. Tacrolimus)
• CDISC, ADaM and SDTM compliant dataset preparation
• Data analysis for Phase-3 trials involving Non-inferiority, Superiority and Therapeutic / Clinical equivalence comparisons
• Involving single dose, multiple dose with different study designs, over 750 studies have been designed on EDC system
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Module 1
Module 3
Quality
Module 4
Nonclinical Study Reports
2.7 Clinical Summary
Module 5
Clinical Study Reports
2.6 Nonclinical Summary
2.4 Nonclinical Overview
• Oncology
• Dermatology
• Musculoskeletal
• Cardiology
• Gastrointestinal
• Diabetology
• Respiratory
Therapeutic experience Complying with all current regulatory requirements
REPORT WRITING CREDENTIALS
Quality Overall
Summary
2.5 Clinical Overview
Regional Admin
Information
LAB - ACCREDITATIONS & OFFERINGS
BIOMARKERS & BIOSIMILARS
ASSAY DEVELOPMENT
IMMUNOGENICITY
SAFETY TESTING
ANTI MICROBIAL/ HYGIENE
CAP ACCREDITED SINCE 2005
(College of American Pathologists)
NABL (ISO 15189:2007) SINCE 2010
• First lab in India for Immunogenicity testing services for Biosimilar • Half a million tests performed/year
CAPABILITIES
Immunogenicity
Hematology
Immunology
• Special Cell Culture lab. • BioSafety Cabinet
Neutralizing
Antibodies
•Davinci Quatro (fully automated ELISA processors)
• Serology Testing [HIV, HBsAG, HCV, Infectious markers, Hormonal assays etc.] • COBAS e411 (ElectroChemiluminescence) • VITROS ECI from J&J (Chemiluminescence) • Davinci Quatro (fully automated ELISA processors) • Synergy HT Plate Reader (Biotek)
• CBC (Fully automated Sysmex, XT-2000i) • ESR (Fully automated SRS 100/II) • Platelet Aggregometer (Chronolog) • Urine analysis (Fully automated Urisys2400 Roche) • Immunophenotyping (BD, FACS-Calibur) • Coagulation studies (STA-Compact, Stago)
CLINICAL LABORATORY
CO2 Incubator
Anaerobic Incubator
Spiral Plater + Spiral Reader Platelet Aggregometer
RT-PCR
• Amongst the few labs. in India to own a Spiral Plater, Anaerobic & CO2 Incubators
• Covers all specialties of clinical
lab. tests & supports pan-India
Trials as a Central Lab.
EXPERIENCE - INVITRO STUDIES
• Anti-microbial efficacy comparison of toothpastes containing triclosan against
Streptococcus mutans using in-house developed method of “Time kill assay” by
using HAP disc. Antimicrobial activity can be compare up to 12 hrs. Helps in claim
support and also during formulation of new products.
• Anti-microbial efficacy comparison of toothpastes containing triclosan by using
Streptococcus mutans using MIC Method (Minimum Inhibitory comparison). Helps
in claim support and also during formulation of new products.
• To evaluate the ability of toothpaste to reduce the amount of acid generated by
oral bacteria in presence of excess glucose by using “Salivary sediment pH drop
method” using hydroplates.
• Efficacy of the dentifrices evaluation by studying BDCOH (4, 4’-bis
(dimethylamino) diphenylcarbinol) levels in saliva. BDCOH an indicator of the level
of mal odour. Helps in claim support against Bad breath (Mal odour).
• 1000+ Database of Clinical Sites & Investigators
• Successful USFDA inspection at 23 Indian sites
• Bespoke Services
• Experienced with 20+ TCs
CLINICAL TRIAL MANAGEMENT (CTM)
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50%
3% 6%
23%
9%
3% 6%
Oncology
Musculoskeletal
Gastrointestinal
Psychiatry
Respiratory
Gyneacology
Dermatology
NETWORK OF INVESTIGATIONAL SITES
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5
20
50
17
15
43
60
20
65
15
45
20
10
44
0 10 20 30 40 50 60 70
Others
CNS
CVS
Arthritis & Pain
Dermatology
Endocrinology
Respiratory Disorder
Oncology
Opthalmology
Gasteroenterology
Pediatrics
Diabetology
Infectious diseases
ENT & Allergy
Th
era
pe
uti
c S
eg
me
nts
No. of Sites
18 Successful USFDA site inspections from year 2009 to 2014
Europe: • Poland • Estonia • Latvia • Lithuania • Belarus • Ukraine • Romania • Bulgaria • Czech Republic • Germany • France • Spain
India: • Andhra Pradesh • Bihar • Delhi • Gujarat • Haryana • Himachal Pradesh • Karnataka • Kerala • Madhya Pradesh • Maharashtra • Punjab • Rajasthan • Tamil Nadu • Uttar Pradesh • West Bengal
Investigator Sites
Asia: • Sri Lanka • Bangladesh • Taiwan
(* Many countries are covered by our own CRAs, in some countries freelance CRAs or partner CRAs)
New geographies • CIS countries • South East Asia • Latin America
North America • Canada • USA
GLOBAL NETWORK
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CASE STUDY
• RHEUMATOID ARTHRITIS
• 15 patients enrolled in just 4 months from 10 sites
• Screen failure rate expected was 20% due to TB gold test criteria
• Total of 175 patients screened and 115 enrolled in 6 weeks time
• In-spite of high screen failure rate, recruitment completed well before time
• ONCOLOGY
• Planned target : 42 patients in 4 month from 6 sites
• Nature: Timeline critical for USFDA submission
• Change in protocol design by sponsor additional approval from all sites EC + regs only one month available for recruitment
• Extensive recruitment planning ensured completion in 4 weeks and report submitted 1 week before original committed timeline. 25
• Lambda Imaging Central Review PACS system
• “Validated” & 21 CFR Part 11 compliant
• Complete Audit trail till Data Export
• Automated calculations
• In built error checks to prevent reviewer mistakes
• Customizable iCRF: RECIST 1.0 / RECIST 1.1, IWG, iIRC, vDH etc. criteria
• iCRF for specific assessment criteria for Oncology, MSK, CNS, CVS etc.
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MEDICAL IMAGING
IMAGE PROCESSING @ LAMBDA
• Images Received • Tracker checked • Images to Server • Quality Assurance
• IAM compliance • Confidential info
Accept or
Query
• QC 2 (unique ID) • Study specifics • Any Prelims
REVIEW
HOW IMAGING HELPS
Conventional Endpoints Imaging Endpoints Benefit
Subjective Objective Data Validity
Qualitative Quantitative More Precise
Potentially BIASED BLINDED Higher Confidence
Time consuming FAST SAVES TIME!!!
Examples:
Tumors Patient Survival
RECIST IWG 2007 criteria
Accelerated Approval
Rheumatoid Arthritis Patient pain & function diary
MRI for joint space, erosion & inflammation
Faster changes, Reproducible data
PHARMACOVIGILANCE SERVICES AT LAMBDA
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UK (HQ)
Poland (Local
literature surveillance)
Canada (US Call centre)
AHM PV (Global
back-end operations)
OPERATIONS – ‘HUB & SPOKE’ MODEL
LAMBDA PHARMACOVIGILANCE SUMMARY
• The global safety team comprises of Physicians, Pharmacists and PV specialists
(150+ Globally) with wealth of therapeutic expertise, to provide proficient services
for client’s products (~200 plus active moieties).
• Proprietary, Cost effective, customizable, user friendly, regulatory compliant web
based database PvNET.
• Experienced at low risk transitions of PV responsibilities for products with change of
ownership with expertise in handling legacy data
• Highly scalable: 3 months is the optimal lead-time period for you to effectively plan
and resource for an increase in volume
• Help you to achieve sustainable cost savings
• Successfully underwent multiple Regulatory and Vendor audits for PV functionality.
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Our Global Presence
Study Design Phase of the Trial: Clinical Study
Name of the Drug: Confidential
Indication: Food study
Objective Identification of one or more flour composition(s) that give a statistically significant reduction in positive incremental area under the plasma glucose curve (+iAUC0 120 min), relative to the control product by at least 40 mmol. minutes
The effect of the study products on positive incremental area under the serum insulin curve (+iAUC0-120 min)
No. of subjects 56 (male and female)
Outcome Positive results obtained @ Lambda helped the sponsor decide future strategy for the product
Current status – Client is already working @ second level of product development program
OTC/NEUTRACEUTICALS CASE STUDY 1
Study Design Phase of the Trial: Clinical Study
Name of the Drug: Confidential
Indication: Food study
Objective Reduction in venous post-prandial blood glucose (PPG) positive incremental area under the venous glucose versus time curves, during the 2 hours after study product intake (+iAUC0-2hours)
Insulin lowering effect (tAUC0-2hours) of extract added to different types of rice
No. of subjects 120 (male and female)
Outcome Positive outcome
Expected to move from level 3 to level 4 of sponsor’s product development program
Diversified product line offering also planned based on this study’s results
OTC/NEUTRACEUTICALS CASE STUDY 2
Study Design Phase of the Trial: Clinical Study
Name of the Drug: Confidential
Indication: Oral Care
Objective Anti-bacterial effect evaluation of toothpaste by checking viability of bacteria – Total viable bacterial count (Aerobic and Anaerobic), Streptococcus mutans, Anaerobic Streptococci measured in plaque samples taken 4h post intervention, and in saliva samples taken 2h and 4h post intervention
No. of subjects 45 (male and female)
Outcome Conclusive data generated by Lambda for the legal case
Legal case: Court ruled in sponsor’s favor
Claim now part of a famous oral care advertisement
CASE STUDY 3
• Physically present: India, UK, Europe, North America Global footprint and world class
infrastructure
• End to End: Phase 1 / BA/BE / Late Phase / Bioanalytical / CDM / Central Laboratory / Pharmacovigilance / Medical Imaging
Customized full spectrum services
• Clearances from all major regulatory bodies Impeccable Regulatory track record
• Live database of healthy and patient populations Large Volunteer Database
• BA/BE studies and Phase I to IV clinical trials EDC Platform
• Capability to handle large multi-centric trials Late Phase Studies
• Biosimilars / Vaccines / Nutraceuticals / Cosmetics Niche expertise
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ADVANTAGE LAMBDA
CONTACT US
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• Global:
Dr. Mrinal Kammili Executive Director Global Head-Business Development
Akshaya Nath
Senior Vice President
Global Operations and Business Development
Dr. Nermeen Varawalla Executive Vice President Global Clinical Trials [email protected]
• North America:
Cathy Lopez
Director -Business Development [email protected] Roger Stein Director -Business Development [email protected]
Christopher Ore
Executive Vice President North American Operations [email protected]
• Europe:
Elzbieta Zyto Head-Clinical Trial Operations-Poland [email protected]
• Biometrics
Dr. Kamlesh Patel Associate Vice President [email protected]
• Turkey:
Devrim Sabuncuoglu Manager - Business Development [email protected]
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