Pfizer Laboratories Div Pfizer Inc TRAZIMERA- trastuzumab ...
Pfizer Ray Goff Clinical Trial Presentation (2) (3) · Microsoft PowerPoint - Pfizer Ray Goff...
Transcript of Pfizer Ray Goff Clinical Trial Presentation (2) (3) · Microsoft PowerPoint - Pfizer Ray Goff...
Cold Chain Designfor Mega-Scale Clinical Trial - A Case Study
Ray GoffDirector,
Pfizer Vaccines R&D
1
Clinical Trial Distribution - A Case Study
Great challenge of this mega-scale clinical trial. Trial will be critical to determine the position of conjugate
pneumococcal vaccines in the prevention of pneumococcal disease.
• The burden of community–acquired pneumonia (CAP) among the elderly ishigh and has increased over the last decades. CAP ranks among the top-5causes of death for the elderly.
• The primary objective of the planned trial entitled CAPiTA (Community Acquired Pneumonia Immunization Trial in Adults) is to establish the efficacy of 13-valent PnC vaccine in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adult persons aged 65 years and older.
• This trial is performed entirely in The Netherlands.
• More details are published in “ The Netherlands Journal of Medicine,October 2008, Vol. 66, No. 9; Hak, et al. Rationale and design of Community–Acquired Pnuemonia Immunization Trial in Adults.”
2
Clinical Trial Distribution - A Case Study
Great challenge of a mega-scale clinical trial .
Stage 1 Initially enrollment was planned for 85,000 subjects in 6-8weeks. Study was double blinded supply and placebo with temperature controls at 2-8ºC, covered Netherlands country, involved regional hospital associations and public relations. This study will lay clinical knowledge foundation for CAP for adults and is supported by medical academia.
• Uptake of study was slow. At week 5 it became apparent that studyrecruitment would take longer than 12 weeks and extend to possibly 20 weeks -end of year.
Stage 2 The second year brought other challenges with new staff,expanded recruitment areas, larger GP base, and another 56 weeks tocomplete the last 55,500 enrollment.
3
Best Practices
Be Flexible and Adapt to Challenges
Be Risk Conscious - Solution Oriented
Be Assurance Focused- Innovation Driven
4
Steps to Managing Change and Risk
Plan with Partners
Assess Risk
Evaluate Possibilities
Rank Probability / Impact
Propose Plan to Management
Implement Plan (C and/or M)
Manage KPIs
Be prepared to Pro-Act
Update new plan with partners
Implement activities
Adapt to challenges – go back to first step
5
Partner Team
6
Stage 1 Cold Chain & Secondary Packaging
Weeks 1 thru 5 shipments were in insulated product carriers (51minutes @ 22C) stacked inside pallet shipper inside temperaturecontrolled 40ft tractor trailer. The pallet shipper filled with carrierswas later transferred to temperature controlled vans.
Weeks 6 thru 12 shipments were in upgraded insulated carriers(6 hrs @ 23C) stacked inside temperature controlled 40ft tractor trailer. Insulated carriers were then loaded into temp controlled van. Pallet shipper eliminated due to drop in volumes.
Weeks 2 thru 8 air shipments used nomadic shipper (thickpolyurethane shipper rated at 48 hrs and weighing 54lbs.). Upon arrival at Netherlands airport shipper was transferred to temperature controlled vans.
7
Cold Chain & Secondary Packaging
Product required 2-8C temperature control
3 Thermal Layers designed into Study
Vehicles (temperature controlled)
Pallet shippers (insulated and cooled)
Insulated Containers
8
Stage 1 Distribution Overview
156 shipments from UK to few sites in NL.
Ground / sea from 40ft tractor trailer to sprinter vans across ferry to EU and on to clinical sites. Air shipment from UK to Cologne to NL.
Week 1 thru 5 large quantities to a few sites - concept was large, quick, centralized and consolidated. Build stock at site. Study only 8 weeks long.
Week 5 thru 12 smaller quantity and more sites, enrollment tapering off - concept was smaller more outreaching, scattered fixed site locations. Stock only what is likely.
On-going collection of data confirmed Air shipment max 24 hrs and Ground / sea max 32 hrs.
9
Stage 1 Ground Transportation Flow
Warehouse Shuttle Ferry Vans(deliver supplies)
Tractor Trailer
Clinic/Hospitalthen
delivery to homes
Vans(pick up returns)
Shuttle FerryWarehouse Tractor Trailer
Original route planned for 48 hrs.10
Stage 2 Ground Transportation Flow
Warehouse Shuttle Ferry Truck & Vans(deliver supplies)
Luton Truck
Clinic/Hospital
Luton TruckPick-up returns
Shuttle FerryWarehouse Luton Truck
Original route planned for 48 hrs.11
Stage 1 Air Transportation Flow
Warehouse Van Storage Airplane Vans(deliver supplies)
Clinic/Hospital
Vans(pick up returns)
Shuttle FerryWarehouse Tractor Trailer
Original route planned for 48 hrs.12
Stage 2 Air Transportation Flow
AirplaneWarehouse Storage Truck &Vans(deliver supplies)
Van
Clinic/Hospital
Luton Truck
Pick-up returnsShuttle FerryWarehouse Luton Truck
Original route planned for 48 hrs.13
Stage 2 – General Route & Transportation
NL
TransferPoint
Dover
14
Stage 1 Delivery Time Segmentsby Air and /or Ground/Sea Shipments
Total Ground/Sea AirDELIVERY PROFILE
30%
25%
20%
15%
10%
5%
0%
16-17 17-18 18-19 19-20 20-21 21-22 22-23 23-24 24-25
Hours
25-26 26-27 27-28 28-29 29-30 30-31 31-32
15
Stage 2
16
31-32hrs
30-31hrs
29-30hrs
28-29hrs
27-28hrs
26-27hrs
25-26hrs
24-25hrs
23-24hrs
22-23hrs
21-22hrs
20-21hrs
19-20hrs
18-19hrs
17-18hrs
16-17hrs
CAPITA 1 DELIVERY PROFILE
30%
25%
20%
15%
10%
5%
0%
TOTAL GroundSeaAIR
Stage 1 & 2 Delivery Time Segmentsby Air and /or Ground/Sea Shipments
17
TYPES OF SHIPMENTS
Total AIR13%
Total Ground Sea87%
TotalAIR TotalGroundSea
Stage 1 Delivery Time SegmentsAir Shipments
AIR SHIPMENTS DELIVERY TIMES
23-24hrs11%
22-23hrs26%
Up to 17hrs36%
21-22hrs5%
17-19hrs11%
19-21hrs11%
Up to 17hrs 17-19hrs 19-21hrs 21-22hrs 22-23hrs 23-24hrs
18
Stage 1 Delivery Time SegmentsGround/Sea Shipments
GROUND SEA SHIPMENTS DELIVERY TIMES
Up to 24hrs1%
30-32hrs11%
24-26hrs11%
26-28hrs47%
28-30hrs30%
Up to 24hrs 24-26hrs 26-28hrs
19
Stage 2 Delivery Time Segmentsfor Ground/Sea Shipments
1% 0%8%
20
GROUND SEA SHIPMENTS DELIVERY TIMES
26-28hrs 28-30hrs 30-32hrs
24-26hrs33%
Up to 24hrs58%
Up to 24hrs 24-26hrs 26-28hrs 28-30hrs 30-32hrs
Temperature Monitoring Study
Entire study used Sensitech TempTale®4 temperature monitors for vehicles and product containers.
Protocol was written to control placement,database for reporting.
TempTale®4s were placed:
Inside product container
Inside cool compartment of tractor trailer
documentation and
Front of outside tractor trailer for ambient reading
Back of outside tractor trailer for ambient reading
Inside cool compartment of van
Front of outside van for ambient reading
Back of outside van for ambient reading.
21
Temperature Monitoring
Ambient Air Temperature
Van TransportTruck Transport
Ferry Portion of Trip
22
VaccineResearchTemperature Monitoring
Reefer Temperature
0� 18.0�-� � � � ------,>---� � � � � --+-� � � � � � ---+-� � � � � � --+-� � � � � � -+-
� � � � IIID: i . _
�
m: i . _
©
EID�
0...12.0� -� � � -� ,� � � � � � --+� -� -� � � � ---� � � � � � --� � � � � � --� � � � 11
6.0 ---------------------,
------------------------------------------ -------------------------- ---------------------------------- ----------------------------------i-------------------------
I I0.0 ._,,.-.-..-..-..-...-.-..-..-..-..-..-..-..-.-..-..-...-.-..-..-..-..-..-..-.""1""-"'.-.-..-..-...-.-..-..-..-..-..-..-..-..-..-..-.-...-.-..-..-...-.-..-..-..-..-..-..-..-..-.-..-.."""-"-"'-...-.-..-..-..-..-..-..-..-.-..-..-...-.-..-..-..-..-..-..-..-..-..-.-...-.-..-..-....-..;.,-,-..-..-..-..-..-..-..-.-...-.-..-..-...-.-..-..-..-..-..-..-..-..-.-..-...-.-..-..-..-...-.-..-..,j,o,-,o-,,-,..-.-..-..-...-.-..-..-..-..-..-..-..-..-..-.-...-.-..-..-...-.-..-..-..-..-..-..-..-!!!!1!!!O-j,,,..-.-..-..-...-.-..-..-..-..-
..-..-..-..-.-..-...-.-..-..-..-�-I
10/21f2.08 6:00AM 10/21f2 812:00PM
10/22[2.0 812:00 AM
10/22[.20 8 16:00 AM
Date /Time
23
Temperature Monitoring
Product Temperature
Truck Transport Van Transport
24
VaccineResearchTemperature Monitoring Design
Typical Temperature Dataset for each Shipment
3 0 . 0 � - - - - � - - - - - - � - - - - - - � - - - - - � - - - - - - � - - - - �
0�©: I , _
�
1s.o�----------+--------------+--���-------l#--�.��l'----------+-------l�-------+--nl�-���-·1
ro: I , _
©
E©I -
0...
l 2.0--1- - - - -i11r----+----lf-"'---,, ,,�
10/21 f.2008 16: 0 AM 10 /22[2.0. 812:00 AM 10 /22[2 .· 8 6:00 AM
Date/ T ime
25
Stage 1 Temperature Study Findings
Product temperatures are in excellent range.
44% of shipments would have been an excursion if thermallayer around the product was not present. Vehicle reefer withproduct alone is not enough.
The start temperature has large impact on when productgo beyond alarm limits. Pre-conditioning of coolant and assembly is critical.
will
26
Stage 1 Product TemperaturesGround/Sea Shipments
27
Stage 2 Product TemperaturesGround/Sea Shipments
28
29 29
2 Temperatureshipments
Stage Scatter Diagramfor 255
August OctoberSept
Stage 2 Distribution Overview
255 shipments from UK to NL sites.
Ground/ sea from Luton truck to sprinter vans across ferry to EU and on to clinical sites
Air shipment from UK to NL
Week 1 thru 32 small volume and more scattered sites, progressive roll-out enrollment, hybrid concept was smaller more outreaching, scattered fixed sitesthroughout EU country, mobile medical units (MMU) to support small enrollment locations. Stock only what is likely. Manage logistics and inventory weekly.
30
Stage 2 - Cold Chain and Secondary Packaging
Week 1 thru 32 shipments are in insulated product carrier (6hrs @ 23C) stacked inside temperature controlled Luton Truck.The pallet shipper and 40ft Tractor trailer were eliminated. Thecarriers are later transferred to temperature controlled vans.
Air shipments used Polar Thermal 48 hr shipper. Reusable Polartherm bags rated for 48 hrs and weighing 26lbs. Upon arrival at EU country they were transferred to ambient or temperature controlled vans. Bags picked up weekly by returns Luton truck.
Fuel prices at end of Stage 1 were 3x of start price and Stage2 started at 3x and went to 5x. Today it is at 2.5x start price. Carrier bag upgrades and vehicle decisions negated impact of fuel price increases
31
Results
Improvements-
Distributions: Loop method & lowered delivery time under 24 hrs,Supply Planning: improved communication and accuracyCold chain - Zero shipping excursions and proof of performance Risk Avoidance- plans in place for top risk concerns Temperature/ shipping information database
Sustainability-
Re-useReduce carbon footprintAvoid carbon footprint
Cost savings- Over five hundred thousand dollars. If designed as a traditional study- at least a million dollars
Cost avoidance- No shipping excursions, over two hundred thousand dollars. Lower site inventory, over three hundred thousand dollars
32
Design Stage 1 & 2Mega Scale Study - Challenges
Size of study, number of subjects & sites
Speed to conduct study,
Outsourcing and internal level of control (turnover)
Supplies
inventory
temp control & cold chain
expiration dating
Temperature profile (season and geography)
Mode / route of transportation air, sea, and ground (strikes)
Distribution Network vs. geography of sites (weather delays)
33
Shipping Excursions
Shipping excursion rate for this Mega-study = 0%
Pfizer
Pfizer
Pfizer
Vaccines
Vaccines
Vaccines
R&D
R&D
R&D
for last 2 years in EU = 1.2%
worldwide rate = 2.6 %
before 2006 = 4% to 15%
Percent of shipments exceeding 2-8◦ C = 21% to 92%Representative sample of 1,000 non-Clinical GMPshipments
*Sensitech shipping study data – Internal Document
Average cost of one (SE) shipping excursion = $ 3,137 plusleast 48 staff labor hours (2007 currency)
Average study SE cost = $ 150,576 and 2,304 staff hours
at
34
Packaging
35
Adapting Distribution to Site Inventory Blocks
IBC- Inventory Block Carton
Lowest loss inventory size for average site.
36
Sustainability Stage 2
•Lightweight for airshipments
•Reusable
•Fits distribution loop
•Greater payloadthan previous
shipper
37
Sustainability & Cold Chain Stage 1 & 2
Carriers easier for drivers and clinics to handle. Lightweight,reusable, improved insulation to cover possible van/truckbreakdown or delay at site. Stage 2 Upgrade to 6 hrs coverage.
38
Cold Chain & Sustainability
PolarTherm Pallet System is made for thermal protection. The palletsystem is thenlater a van.
loaded into a temperature controlled tractor/trailer and
39
Background Slides
40
Results
Process Improvements Distributions: Loop method- transportation already paid for by return activities, lowered majority of delivery time under 24 hrs, Supply Planning: improved by including regional managers in site delivery process, site inventory load became more accurate less loss. Cold chain management -significantly reduced shipping excursions (0%), Risk Avoidance- plans in place for the most likely and most impact events.
Sustainability- Re-use of packaging, return transportation not part of packaging carbon footprint, avoid carbon for new package, avoid carbon for labor and disposal of new packaging and avoid carbon for lower payload and heaver packaging,
Cost savings- Greater payload and lighter weight shipping, fewer total packages purchased and shipped, fewer temperature monitors and documentation. Several hundred thousand dollars.
Cost avoidance- No shipping excursions. Average 4% = over a hundred thousand dollars. Lower site inventory loss by 5% = over two hundred thousand dollars
41