Enabling > Global Pharma March 17, 2010 Pharma & Biotech Supply Chain World Asia Achieving Effective...
-
Upload
daniel-hawkins -
Category
Documents
-
view
217 -
download
0
Transcript of Enabling > Global Pharma March 17, 2010 Pharma & Biotech Supply Chain World Asia Achieving Effective...
Enabling > Global Pharma
March 17, 2010
Pharma & Biotech Supply Chain World Asia
Achieving Effective & Successful Trial through accurate Demand Forecasting of Clinical Supplies
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 22
Speaker Profile
Qualifications- MD in General Medicine, MD in Community Medicine- Diploma in Public Health and Diploma in Industrial Health- Diploma in Management from the Jamnalal Bajaj Institute of Management Sciences
Previous Experience- Dean & Director, Clinical Research Education and Management Academy (CREMA), Mumbai- Professor & Head of Dept. of Community Medicine, Grant Medical College, Mumbai- Vice-Chancellor’s nominee to the Academic Council of the University of Mumbai- Medical Administrator of the Mahatma Gandhi Memorial Hospital- Joint Director of Medical Education & Research- Director of the prestigiousHaffkine Institute, Mumbai- Administrator of Maharashtra Medical Council - a licensing/regulatory body of Govt. of Maharahtra for MBBS doctors Contribution- Two Chapters for the API Textbook of Medicine- 21 published research papers, 7 editorials and 61 articles- Presence at International and National Conferences for Presentation of Scientific Papers- Editorials for journal of Association of Physicians of India- Editor of Indian Journal of Occupational Health and My Doctor
Awards- Has been awarded three orations and WHO Fellowship- Awarded the Best Referee by Journal of Association of Physicians of India (JAPI), for 2007
Dr. Shreekant SapatnekarMedical Director Karmic Lifesciences
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 33
Agenda
Overcoming "supplies stock out" situation through effective demand forecasting
Building an effective aggregate demand forecasting strategy at the distribution point
How to ensure infrastructure of local depot network for clinical supplies is ready to achieve operation and cost efficiency
Achieving effective and successful trial through accurate demand forecasting of clinical supplies
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 44
Introduction to Clinical Trial Supplies Chain
The “Clinical Trial Supply Chain” refers to the activities involved with planning, sourcing, transporting and distributing clinical trial materials including
Investigational Product, Clinical Equipment & Supplies to the Clinical Trial Sites and Investigators
Sponsor/ Manufacturer
Global Carrier Local CarrierCRO
Site 3
Site 2
Site 1
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 55
Illustrative Supply Chain for Clinical Trials
Applicable Import
Application & Approval
Overall IP Trial Related Demand
Forecast calculated by Sponsor/CRO
IVRS portal automatically predicts inventory & minimum
order quantity/Site can manually use
portal/phone to order shipment from Central
Depot
IP Shipped & Received at Airport
IP Stored at Central Supplies Depot
IP Shipped to Site in required shipping
conditions
IP Delivered to Site in controlled conditions
IP Reaches at Site, verified for physical
appearance, temperature integrity,
proper quantity by analyzing data
logger
Investigator maintains IP accountability in IP Log
IP Return/Disposal as per Study
Protocol
Shipment of Clinical trial Supply as per Shipment order from Sponsor including:
Correct Destination for Shipment
Accurate Packaging Condition
Accurate Quantity
Temperature Integrity
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 66
Special Conditions Pertaining to Clinical Trials Supply Management
Requirement to manage the supplies involved in supporting clinical trials Global Trials Multiple Countries & Regulations Multiple Locations Multiple Investigators Multiple Trial Medications/”Drug Kits” Data Collection/Reporting Devices (e.g., PDA’s, cell phones, remote sensors)
Need to coordinate delivery of supplies to multiple active sites Different sites may have different recruitment timelines, recruitment period, rate of
recruitment and no. of patients recruited Randomization of medication administration may trigger resupply at variable intervals
requiring variable safety stock at each site Flexibility and speed of delivery is critical Consideration of special packaging and handling requirements (e.g. cold shipping)
Historical data from older trials to understand IP and supply chain requirements Variability in the number of patients enrolled, number of investigators, geographic
distribution of trials will create larger variability in inventory and distribution of drug kits
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 77
Clinical Trial Supplies Challenges
Randomization/
Stratification
Variable Enrolment & Drop-Out
Rate
Complex Regulatory
Requirements
Cold Chain Transport
Multiple
Distribution
Interfaces
Expiration
Dating/Disposal
Multiple
Dosing/Weight
Based Dosage
Adaptive Trial Design
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 88
Clinical Supply Chain
Optimization
Clinical Supply Chain Optimization
$Risk 100% Protocol
Adherence
Avoid Stock-Outs
Avoid IP Spoilage
Optimized Transport Costs
Optimized Storage Costs
Optimized Re-Order Frequency
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 99
Framework for Managing Effective Clinical Supplies
No. of Patients No. of Sites Correct IP Dosing
Determination (Multiple/Weight Based etc.)
Duration of Treatment
Patient Randomization
Patient Recruitment Rate
Patient Drop-out Rate
Back-up Site Supplies
Type of Medication
Source of IP Procurement (COA etc.)
Supply Lead Time
Delivery Conditions
Type of Packaging
Country Of Shipment
Import Regulations
Mode of Transport (Air Connectivity)
Time to Shipment
Storage Conditions during transit (Cold Chain etc.)
Local Support for clearing
Type of Medication
Storage Conditions as per Study Protocol
Drug Stability Capacity
Limitation Disposal as per
Protocol Disposal Facility Hazard to
Environment Documentation
Accurate Demand
Forecasting
Transport in Controlled Conditions
Robust Site Inventory
Mgmt
Proper IP Storage & Disposal
Correct Procurement
Patient Randomization
Patient Recruitment Rate
Patient Drop-out Rate
Use of IVRS for Automated Inventory Mgmt
Back-up Site Supplies
Supply Lead Times
Advance “Stock-Out” Intimation
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1010
Accurate Demand Forecasting Overcoming “Supplies Stock-Out” Situations
Safety Stocks Calculating Safety Buffers Accurately based on previous statistics and data
Minimum Stock Level for Re-order Determining appropriate Trigger Points for Stock Re-Order
Cognizance of Supply Lead Times Integrating Supply Lead Times with Re-Order Trigger Points
Cognizance of IP Expiry Dates Factoring IP Expiry Dates into Demand Forecasting
Close Monitoring of Recruitment & Drop-out Rate at Sites Monitoring of recruitment & drop-out rates Updating demand forecast for next 90 days
Use of IVRS/IWRS Automated Inventory Management, Patient Randomization, Visits & Related IP Usage Seamless integration from Central Storage to Sites Trigger-Based: Min/Max Stock Levels Predictive: Safety Stock + Prediction Window
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1111
Accurate Demand Forecasting Aggregate Demand Forecasting Strategy at Distribution Point
Use of Demand Forecasting, Decision Modeling Tools & Monte Carlo Simulation
Determining correct overall IP quantity IP Unit Packaging Weight & Volume Calculations Dosing Schedule/Multiple Dosing Weight Based Dosing
Determing IP quantity for individual sites Planned Recruitment Rates Planned Drop-Out Rates
Provision for moving IP to rescue sites Monitoring of recruitment & drop-out rates Updating demand forecast for next 90 days
Calculating Safety Stocks Provisioning for Buffers
Superimposing IP quantity on weekly time scale
Refining and updating forecast on a weekly basis
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1212
Safety Stock
Q
0
Illustrative Demand Forecasting at Central Depot & Sites
Safety Stock
Q
0
Safety Stock
Q
0
Safety Stock
Q
0
Safety Stock
Q
0
Safety Stock
Q
0
Investigational site
Investigational site
Investigational site
Investigational site
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1313
Managing Clinical Supplies for Cost & Operational Efficiency Ensuring Robust Infrastructure of local depot network for clinical supplies
Infrastructure Specifications Space Requirements Storage Requirements Cold Chain Packaging Distance Connectivity IT & Technology Automation (Tracking, IVRS etc.)
Vendor RFP & Selection Get capability data & quotes from multiple vendors Select highest quality vendor Negotiate bulk costs
Training of Local Depot Staff Processes Systems
Defined Depot Workflow Defined Workflow & Process Chart Defined Shipment Frequency (Days/No. Of Pick-up/Drop times etc.)
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1414
Continuous Data Generation, Tracking, MIS & Analysis of SLAs
Use of Web Based CTMS/IVRS
Clinical Supplies Operational Reports Supplies Shipped Supplies Used Supplies Expired Supplies Returned No. Of Inventory Turns Frequency of Order Stock-outs faced
Clinical Supplies Cost Reports Shipping Costs Local Storage Costs’ Expiry Costs Costs Per Patient
Managing Clinical Supplies for Cost & Operational Efficiency
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1515
Key Statistics $ 300 Mn Clinical Research Industry 1200 ongoing clinical trials $ 1.2 Bn Clinical Research Industry by 2012 growing at a 40% CAGR 1.3 Bn Patient Population, more than 70% treatment naïve 1500+ hospitals with potential for clinical research activities 31,000+ medical graduates and 700,000 science graduates pass out every year
India Advantages Faster, cost-effective studies
~ 30% reduction in trial completion timelines with extremely fast patient recruitment ~ 50-60% cost reduction compared to other locations including USA and Europe Large treatment-naive patient population with a population of 1.3 Bn+ Strong, well-credentialed physician base with 1 Mn+ qualified and practicing doctors Strong ICH-GCP Compliance and increasing quality levels at par with global standard Government Initiatives and support via an increasingly progressive regulatory environment
Key Statistics $ 300 Mn Clinical Research Industry 1200 ongoing clinical trials $ 1.2 Bn Clinical Research Industry by 2012 growing at a 40% CAGR 1.3 Bn Patient Population, more than 70% treatment naïve 1500+ hospitals with potential for clinical research activities 31,000+ medical graduates and 700,000 science graduates pass out every year
India Advantages Faster, cost-effective studies
~ 30% reduction in trial completion timelines with extremely fast patient recruitment ~ 50-60% cost reduction compared to other locations including USA and Europe Large treatment-naive patient population with a population of 1.3 Bn+ Strong, well-credentialed physician base with 1 Mn+ qualified and practicing doctors Strong ICH-GCP Compliance and increasing quality levels at par with global standard Government Initiatives and support via an increasingly progressive regulatory environment
A recent survey led by 'A.T. Kearney' ranks India very close, or even slightly more advanced than China, due to the progressive regulatory environment and commitment to tight timelines; allowing global biopharmaceutical companies the ability and confidence to conduct clinical trials in country.
A recent survey led by 'A.T. Kearney' ranks India very close, or even slightly more advanced than China, due to the progressive regulatory environment and commitment to tight timelines; allowing global biopharmaceutical companies the ability and confidence to conduct clinical trials in country.
Historical 2003-04 2005-06 2006-07 2008-09
No. of Trials ~200 221 1070
Est. Size ($ Mn) 60 95 150 300
Clinical Trials in India
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1616
India Clinical Supply Chain Highlights
Clinical Trials Import Regulations T-License from DGFT for all clinical trials Application made along with DCGI Form 44 Application Processed in 4 weeks
Samples Export Regulations ICMR Norms for export of samples including tissue, blood, plasma samples etc. Approval for specific sample exports
Transport Infrastructure Presence of Global Carriers including World Courier, Blue Dart, DTDC etc. Use of Cold Chain and transport in dry ice conditions as necessary Few Central Labs have own local transport & supply chain infrastructure e.g.
Metropolis
IT Infrastructure Automated Tracking Use of Data Loggers Use of IVRS increasing
Site Storage Infrastructure All large clinical sites have -2 to -8 and upto -80 degree cold storage facility Most Sites have IT & Telecom infrastructure for use of IVRS
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1717
Dummy/Dry Run carried out (i.e. Dummy IP is sent to the
site with the temperature logger in the shipment)
IP Quantity Calculation IP distribution per site (No of patients * Duration of
Treatment)
IP T-License Procurement & Import
IP Delivered @ the Airport with appropriate storage
conditions
IP Delivered @ Karmic with appropriate storage
conditions
IP Accountability, Storage & Site requirement calculation
Sites informed about Dry Run
IP shipment checked at sites for transit time, breakage,
storage conditions etc.
If Favorable Results
Reporting the results on “0” min
Root Cause Analysis
IP distributed to Trial Site(s) as per quantities calculated
NO
YES
Karmic Clinical Supply Chain Management
IP Dispatched to Site
Corrective Action
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1818
Illustrative Clinical Supplies Case Study
Study Description No. of Patients: 210 Phase : III Therapeutic Area:
Oncology Screen failure: 25% Patient drop-out rate:
15% Treatment Groups: 2 Dose Level: 2 Study-Level
Randomization Weight-Based Dosing Kit Types: 2 Product Storage
Conditions: -2 to -8
degrees C Product Shelf-life: 12
months IVRS Method: Predictive
Karmic Approach Import License from DGFT procured in 4 weeks IP reached Mumbai airport in cold chain with proper packaging and
storage conditions Karmic team had informed Sponsor of Custom Clearance process
as well as a local festival holiday well in advance and requested them to make necessary arrangements to store the study drug at the airport for 48 hours before custom clearance
Karmic further got exact no. of boxes and packaging dimensions for the consignment in advance as well for planning shipping to sites
Custom clearance formalities were completed after the holiday was over. Karmic personnel were personally present to collect shipment at clearing house and the study drug was transferred within 4 hrs from the airport to Karmic’s outsourced Central Storage Depot within controlled conditions
The Central Storage Depot made necessary arrangements to unpack the consignment, make smaller batches and ship pre-determined initial order quantities to the sites on the same day through the use of the local carrier. The shipment was done in controlled cold chain conditions using dry ice and data loggers
The balance study drug was stored at -2 to -8 degrees for a period of upto 12 months post which the IP would expire
The average time for the study drug to reach at site was 14+ hrs (including air transport and local transfer). All the sites received the study drug as per the appropriate condition with “Zero” damage.
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 1919
Key Steps for Success
- Start forecasting at the time of regulatory application.- Identify shipment services provider and documentation well before study
approval from regulatory agency- Site inspection and feasibility report for IP Management- Training for the Site & IP handling staff
Planning
- Provide study medication type and storage condition to courier service provider so that it will help for good packaging and shipment to different trial location
- Identify the cycles of shipment to all study sites.- Target time to reach final destination (Study site) Therefore Tracking
Procurement
- Site selection strategy should incorporate special transport regulation requirement of local region (e.g. 2 different rules for Octroi duty; UP vs. Bengal)
- Site selection strategy should include air and local transport facility- Confirm the temperature requirements during shipment and local transit
before initiating the shipment process- Before shipment initiation, find out local holiday and weather conditions
Transport
- Consider storage facility at site and make necessary arrangement before study supply shipment reach to site including training
- Conduct a dry run before sending actual the study supply at sites - Disposal facility should be available near site- Disposal facility should comply with local Environmental Laws- Adhere to SOPs for disposal of surplus- Check list of documents to be produced before & after supply disposal
Storage & Disposal
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 2020
Conclusion
Supply Chain Management in Outsourced Clinical Research
conducted by a CRO is a challenge of moderate degree
Criticalities are few but important
Modern techniques like Demand Forecasting, Use of IVRS/IWRS
and IT based Tracking are essential
Human behavioral factors as important as the external factors
that result in uncertainties. These must be considered in the
planning and training process
Anticipation of pitfalls, planning, capacity building, adherence to
SOPs and constant monitoring can address most of the issues
Neither easy – nor difficult. Doable with specific inputs.
LKE
nab
lin
g >
Glo
bal
Ph
arm
a E
nab
lin
g >
Glo
bal
Ph
arm
a
Copyright @ Karmic Lifesciences 2010Copyright @ Karmic Lifesciences 2010 2121
Thank You
Enabling > Global Pharma
Dr. Shreekant Sapatnekar
Medical Director
Karmic Lifesciences Tel: +91-22-32597223 (D)
+91-22-25650404 (O) Ext. 215
+91-22-25610403 (F)
+91-9833192331 (M)
E-Mail: [email protected]
Web: www.karmiclifesciences.com