LAMBDA THERAPEUTIC RESEARCH

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
1
GLOBAL PRESENCE
Warsaw, Poland
2007
London, UK
2008
Ahmedabad, India
1999
Mumbai, India
2003
Toronto, Canada
2010
New Delhi, India
2009
Istanbul, Turkey
2011
Hyderabad, India
2009
Bangkok, Thailand
2011
2
COMPREHENSIVE SOLUTIONS
EXPERIENCE
MEDICAL IMAGING
E-SUPPORT
SERVICES
100
90
80
70
60
50
40
30
20
10
0
phase I/BA -BE
PHASE II
PHASE III
PHASE IV (PMS)
Pharmacovigilance
3
REGULATORY INSPECTIONS
OGYI [01]
POLISH [01]
AGES [01]
ANVISA [07]
US-FDA [30]
EMA [01]
Thai MOH [03]
CDSCO [12]
WHO [03]
TURKEY MOH [01]
CAP [06]
ANSM [02]
UK-MHRA [04]
PHSS [01]
HEALTH CANADA [01]
4
TIME EFFICIENCIES-ACTUALLY RESEARCH ACCELERATED…
100
80
60
40
20
0
Lambda
Company X
5
SERVICES
LAMBDA
6
GLOBAL CLINICAL BED FACILITY & VOLUNTEER DATABASE
In-house facility of 600+ beds in clinic, including 36 Phase-I and 12 ICU beds
Sr.
No
Country
1
India
2
Canada
City
No. of Beds
Phase I Beds
ICU Beds
Ahmedabad
360
16
8
Mumbai
65
-
2
Toronto
122
12
-
Global database of over 150K volunteers comprising of healthy male, female and geriatric
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
Population
Software – Biometric method for volunteer identification, BizNET for clinical operation
7
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
8
PHASE-I
Infrastructure
Study offerings
•
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
SAD – MAD studies
PK / PD Studies
Drug – Drug Interaction
Drug – Food interactions
MAD
18%
SAD
20%
Food-Drug
interaction
12%
DDI
12%
First in
Man
38%
TC EXPERIENCE
Live attenuated H1N1
influenza vaccine, 1
Inactivated H1N1 influenza
vaccine, 1
Anti Asthmatic drug, 1
NCEs, 5
Anti obesity drug for
Metabolic syndrome, 1
Anti cancer( receptor
modulator), 1
Immunosuppressant, 1
Anti Infective agent, 6
Hormonal agent, 1
Lipid Lowering
agent, 3
Antifungal drug, 1
Anti diabetic drug, 2
Anti Hypertensive agent, 3
Multiple Sclerosis, 1
Alzheimer’s
disease, 6
BIO ANALYTICAL 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
11
BIO ANALYTICAL USP
•
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
12
BIO ANALYTICAL STRENGTHS
•
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
13
CLINICAL DATA MANAGEMENT SYSTEM
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
BIZNET
14
CDM & BIOSTATISTICS SERVICES
CDM
BIOSTATISTICS
•
CRF / eCRF designing
•
Sample size and Study Design
•
CRF annotation as per CDISC
•
Protocol inputs / review, SAP & mock shells
•
Data Management Plan
•
Statistical analysis & reporting
•
Database designing and UAT with
dummy data
•
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
•
Data validation & Query resolution
•
External data upload & cleaning
•
TMF management
•
EDC Training for the site personals
BizNet BENEFITS
•
•
Cost Effective (~ 60%)
Locally available System Support
15
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
16
REPORT WRITING CREDENTIALS
Complying with all
current regulatory
requirements
Module 1
2.4
Nonclinical
Overview
Quality
Overall
Summary
Quality
Therapeutic experience
Regional
Admin
Information
2.6
Nonclinical
Summary
Nonclinical
Study Reports
Module 3
Module 4
2.5
Clinical
Overview
2.7 Clinical
Summary
Clinical
Study Reports
Module 5
•
Oncology
•
Dermatology
•
Musculoskeletal
•
Cardiology
•
Gastrointestinal
•
Diabetology
•
Respiratory
LAB - ACCREDITATIONS & OFFERINGS
BIOMARKERS &
BIOSIMILARS
CAP ACCREDITED
SINCE 2005
IMMUNOGENICITY
(College of American Pathologists)
ASSAY
DEVELOPMENT
NABL (ISO 15189:2007)
SINCE 2010
ANTI MICROBIAL/
HYGIENE
SAFETY TESTING
• First lab in India for Immunogenicity testing services for Biosimilar
• Half a million tests performed/year
CAPABILITIES
Immunogenicity
•
•
•
•
•
•
• Davinci Quatro (fully automated ELISA
processors)
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)
Immunology
• Special Cell Culture lab.
• BioSafety Cabinet
Hematology
• 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)
Neutralizing
Antibodies
CLINICAL LABORATORY
CO2 Incubator
Spiral Plater + Spiral Reader
Anaerobic Incubator
• Amongst the few labs. in India to
own a Spiral Plater, Anaerobic &
CO2 Incubators
Platelet Aggregometer
RT-PCR
• 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).
CLINICAL TRIAL MANAGEMENT (CTM)
• 1000+ Database of Clinical Sites & Investigators
• Successful USFDA inspection at 23 Indian sites
• Bespoke Services
• Experienced with 20+ TCs
3%
Oncology
6%
23%
50%
Musculoskeletal
Gastrointestinal
Psychiatry
9%
6%
3%
Respiratory
Gyneacology
Dermatology
22
Therapeutic Segments
NETWORK OF INVESTIGATIONAL SITES
ENT & Allergy
Infectious diseases
Diabetology
Pediatrics
Gasteroenterology
Opthalmology
Oncology
Respiratory Disorder
Endocrinology
Dermatology
Arthritis & Pain
CVS
CNS
Others
10
20
45
15
65
20
60
43
15
17
50
20
44
5
0
10
20
30
40
50
60
70
No. of Sites
18 Successful USFDA site inspections from year 2009 to 2014
23
GLOBAL NETWORK
Investigator Sites
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
North America
• Canada
• USA
Asia:
• Sri Lanka
• Bangladesh
• Taiwan
New geographies
• CIS countries
• South East Asia
• Latin America
(* Many countries are covered by our own CRAs, in some countries freelance CRAs or partner CRAs)
24
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
MEDICAL IMAGING
•
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.
26
IMAGE PROCESSING @ LAMBDA
REVIEW
• Images Received
• Tracker checked
• Images to Server
• Quality Assurance
• IAM compliance
• Confidential info
Accept
or
Query
• QC 2 (unique ID)
• Study specifics
• Any Prelims
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!!!
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
Examples:
PHARMACOVIGILANCE SERVICES AT LAMBDA
29
OPERATIONS – ‘HUB & SPOKE’ MODEL
UK
(HQ)
AHM PV
Poland
(Local
literature
surveillance)
(Global
back-end
operations)
Canada
(US Call
centre)
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.
Our Global Presence
31
OTC/NEUTRACEUTICALS CASE STUDY 1
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 2
Study Design
Phase of the Trial: Clinical Study
Name of the Drug: Confidential
Objective
Indication: Food study
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
CASE STUDY 3
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
ADVANTAGE LAMBDA
Global footprint and world class
infrastructure
Customized full spectrum services
• Physically present: India, UK, Europe, North America
• End to End: Phase 1 / BA/BE / Late Phase / Bioanalytical / CDM
/ Central Laboratory / Pharmacovigilance / Medical Imaging
Impeccable Regulatory track record • Clearances from all major regulatory bodies
Large Volunteer Database
• Live database of healthy and patient populations
EDC Platform
• BA/BE studies and Phase I to IV clinical trials
Late Phase Studies
• Capability to handle large multi-centric trials
Niche expertise
• Biosimilars / Vaccines / Nutraceuticals / Cosmetics
35
CONTACT US
•
Global:
•
Cathy Lopez
Director -Business Development
[email protected]
Dr. Mrinal Kammili
Executive Director
Global Head-Business Development
[email protected]
Roger Stein
Director -Business Development
[email protected]
Akshaya Nath
Senior Vice President
Global Operations and Business Development
[email protected]
Dr. Nermeen Varawalla
Executive Vice President
Global Clinical Trials
[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]
North America:
•
Turkey:
Devrim Sabuncuoglu
Manager - Business Development
[email protected]
36
37