validation & post validation monitoring reefer validation done right david ulrich abbott...
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Validation & Post Validation MonitoringReefer Validation Done Right
David UlrichAbbott Laboratories, QA Distribution Manager
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What is Validation?
According to the Food and Drug Administration (FDA), the goal of validation is to:
“[Establish] documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.”
- FDA, Guideline on General Principles of Process Validation
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How do we Validate?
FDA’s Center for Drug Evaluation & Research (CDER) General Principles of Process Validation:
Installation Qualification (IQ)
Insures that the system/equipment and its components are installed correctly and to the original manufacturer’s specifications.
Operational Qualification (OQ)
The OQ, tests are performed on the critical parameters of the system/process. These are usually the independent and/or manipulated variables associated with the system/equipment
Performance Qualification (PQ)
This phase tests the ability of the process to perform over long periods of time within tolerance deemed acceptable.
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Validation is NOT new for Pharma Mfg’ers (nor the FDA)
We currently execute validations on:
Methods, Assays, cleaning, recovery, E/U/F, computers, water systems (PW, DW, PO, WFI, etc), Lab instruments, etc
Processes (process validation); fill/finish mfg’ing, RO units, steam sterilization, EtOH sterilization, endotoxin removal, viral clearance, model virus studies, etc
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Good Distribution Practices (GDP)
Good Import Practices (GIPs)
Good Cold Chain Practices (GCCPs)
Distribution Control Systems
(DCS)
GDP
Three maincomponents of GDPs
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Good Distribution Practices (GDP)
Good Import Practices (GIPs)
Good Cold Chain Practices (GCCPs)
Distribution Control Systems
(DCS)
GDP
RF TT, ISS Qualification, “import/Export ”Issues, returns, restock, Reverse Logistics
Complaint mgt, Quality Agreements
GTIN, TnT, ePedigree (RFID),Lot number vs. 1-6-3-3,
Serialization Mfg’ing/MA vs.Dist Control
Beyond Our Boarders,FDA Green lane, Import
optimization (AOCC), RF enabled infoFlow and “supplier supplier” information,
Lacey Amendment, etc
C-TPAT, TSA (CCFS/CCSP)Rules of Origin (COO),10+2 (ocean transport),
Trusted importer program
Congress (Dingle amendment,Kennedy Amendment, etc)And Other Gov’t initiatives
FEI rulechanges
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GDP – Program Overview AQ16-00-GN-001
Ambient Temperature Profiles
Shipping Systems / Shipping Lanes
Shipping Lane Temperature Monitoring
Facilities / Equipment
Validation Master Plans
LSP List
Quality Questionnaires
Quality Agreements
Quarterly Business Review Meetings
Stability Studies
Distribution Website
Exception Management (RCA/CAPA)
Performance Measurement and Reporting
Root-Cause Analysis and Trend Analysis
GTIN, TnT & Serialization
RF enabled temp monitoring
Unit level cumulative temp indicating
Shipping Systems
Regulatory and Industry Trends Monitoring
Benchmarking
Policies / Procedures
Training Modules
Website
Newsletter
Quarterly Management Update Meetings
Qualification / Validation
LSP ManagementProduct Stability
Studies
Performance Measurement and
Reporting
Communication and Education
Continuous Improvement
GDPs are Similar to the other GXPs
Maintain product quality and ensure compliance with global regulations and industry standards for the storage, handling and distribution of temperature-sensitive products
Ambient Temperature Profiles
MKT &PDA TR 39
Shipping Systems / Shipping Lanes
Shipping Lane Temperature Monitoring
Facilities / Equipment
Supply Lane VMP: DQ, OQ, PQ & Supply lane qualification
LSP Mgt
TSP Mgt
Quality Questionnaires
Quality Agreements
Quarterly Business Review (QBR) Meetings
Set and communicate expectations
Stability Studies
Temperature Cycle Studies
“Typical” Supply Chain Excursions
Distribution Stability Website
How to handle cumulative supply chain excursions
Exception Management (RCA/CAPA)
Performance Measurement and Reporting
Root-Cause Analysis and Trend Analysis
Global CAPA effectivity
Quarantine
Returns & restocks
Policies / Procedures
Training Modules
Website
Newsletter
Quarterly Management Update Meetings
Benchmarking & Reaching out to other divisions
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What do we Validate?
Mixers, granulators, mills, grinders, etc
Fluid Bed Dryers (FBDers), RO units, UF units, etc
Sterilizers, Ovens
Software (SQA, SIQ, SOQ, etc)
Manufacturing process of bulk APIs
Manufacturing process of finished goods
Shipment process of finished goods
HVAC units, clean rooms (class 100 hoods), etc
Controlled temperature warehouses
Refrigerated trucks (as part of the E/U/F validation program)
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So how do we (should we) “validate” a reefer truck?
Big “V” and little “v”
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What do we Validate?
Refrigerated trucks are nomore complex
Insulated Trailer
Insulating capacity
Refrigeration unit
Cooling / Heating efficiently
Air flow efficiency
All trailers (Class A, B, C) are all validated the same
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Requirements - CFR Trailer Qualification
Title 7: Agriculture – Can be used for your DQ, IQ, OQ
Chapter XXXIII—Office of Transportation, Department of Agriculture
PART 3300_ATP means the Agreement on the International Carriage of Perishable Foodstuffs and on the Special Equipment to be Used for Such Carriage (ATP),
Sec. 3300.61 Testing and verification requirements.
Sec. 3300.64 “the effective refrigerating capacity, W, in watts, of the appliance at an outside temperature of +30°C and the inside temperature for the class of equipment for which certification is sought”
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Requirements – Industry Standards
Industrial Standardization…
is the process of establishing agreement on uniform identifications for definite characteristics of quality, design, performance, quantity, service, etc.
sets acceptance criteria to meet requirements
maintains process controls and establishes testing methods
For reefer trucks the standard is already in place
So no need to repeat the DQ, IQ, OQ
As part of your quality agreement – make sure your TSP know this AND has acceptable maintaiance
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Validation – The Steps
FDA’s Center for Drug Evaluation & Research (CDER) General Principles of Process Validation (big “V”):
The little “v” componensts of the big “V”
1. Design Qualification (DQ)
2. Installation Qualification (IQ)
3. Operational Qualification (OQ)
4. Performance Qualification (PQ)
5. Process Validation (PV) for the “process”
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Validation – Installation Qualification (IQ)
Vendor’s Data Sheet or Specification required:
Insulating specification or data sheet for the trailer
Refrigeration and heating system specification or data sheet for the trailer
Insures that the system/equipment and its components are installed correctly and to the original manufacturer’s specifications
HVAC on wheels
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Validation – Operational Qualification (OQ)
ATP testing meets OQ requirements:
A trailer’s insulating capacity A trailer refrigeration / heating system must have sufficient
capacity to remove and add heat generated by: Residual heat from the air inside the trailer Exterior heat conducted through the floor, walls and ceiling Infiltration heat from outside air through small holes, cracks and
seals A trailer air circulation system must have sufficient air flow (VOLUME
AND VELOCITY) to carry the heat of the trailer to the refrigeration unit where it can be removed.
Tests are performed on the critical parameters of the system/process. These are usually the independent and/or manipulated variables associated with the system/equipment
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Validation – Performance Qualification (PQ)
This phase tests the ability of the process to perform over long periods of time within tolerance deemed acceptable.
Testing Actual shipments
Run in triplicate
Next steps Post PQ:
Periodic Monitoring
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Reefer Validation – History
What’s been done:
It was suggested that a staggered (wall loading) loading pattern was safer AND would adequately cool
That’s was wrong
Why? Blocked airflow
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Data Review
Actual PQ data review
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Ambient Temps Week of 7-9-07
Chicago Ambient Temperatures
Somerset Ambient TemperaturesAir temperature
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All Monitors 7-9-07 Shipment
•Maximum load of 4 ½ product pallets plus Commodities•Loaded with the Off-set Wall loading pattern
Truck surface temperature
Next to wall
Next to ice bricks
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Current Monitor Locations – based off previous Reefer truck mapping
Blue Line – Pallet A driver side Green Line – Pallet B facing back doors Red Line – Pallet V, last pallet facing doors
Next to wall, first pallet inLong “cool down” time
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Monitors on outsides of pallets
Monitor next to ice bricks, Walls, and on the top of commodity pallets not included.Warmest location – Pallet D up against the wall Coldest location – Last pallet facing the back doors
Long “cool down”Wide “profile”
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External Monitors – Stationary Truck ExternalSurface temp > Ambient air temp
Maximum air temperature was 92 °F (33 °C)
Blue Line – Back door of trailer Green Line – Driver side Trailer wall Red Line – Passenger side Trailer wall
115 °F
Air cooling effect
40 °C
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Monitors on Product Pallets – Wall Loading
Pallet E – next to the ice bricks
Pallet D – Passenger side (against the wall)
Wall loading “blocks” airflow causing long cool down times and variable profile. Not a flat line.
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Monitors on Commodity Pallets
Ambient corrugate doesn’t effect profile
No heat load/sink, therefore, does not effect temperature, BUT loading pattern is still
critical
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Internal on the product pallets – Wall loading
Blue Line – Pallet A Green Line – Pallet B Red Line – Pallet C Yellow Line – Pallet D
Pallet A took 6.5 hours to get within spec.
Wide “Product” temperature profile and long cool down
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Pallet A Monitors – Next to driver side wall
Blue Line – Driver side(against the wall) Red Line – internal to the pallet Green Line – Middle between rows of pallets Yellow Line – Top of pallet
Bad airflow, therefore, > 8 °CPer ASHRAE – airflow is more critical than
temperature
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Monitors on the inside of the trailer walls (6 ft high)
Above 8 °C for 3.5 hours.Longer to achieve acceptable temperature – not optimal
Pallet height was variable from 5 Ft to 7 Ft
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Monitors on pallets up against the walls – Wall Loading
Highest to Lowest Temperature (Maximum Delta of 8.5 °C)Green Line – Pallet D Blue Line – Pallet A Red Line – Pallet E
Yellow Line – Pallet L Light Blue Line – Pallet U
Wall Loading blocks airflow
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TempTales on pallets away from the walls
Highest to Lowest Temperature (Maximum Delta of 2.2 °C)Green Line – Pallet C Red Line – Pallet K Blue Line – Pallet B Yellow Line – Pallet V
Still a long time to cool vs centerline loading (and not a flat line)
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Middle Monitors between Pallets – stayed above temp as long as wall pallets
6 hours above 8 °C
Highest to Lowest Temperature (Maximum Delta of 21°C) Red Line – Pallet U Green Line - Pallet E (next to icebricks)
Next to ice bricks
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What Should be Done
Centerline Loading
Shows that loading pattern is most critical and that set point can be maintained with proper loading pattern
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Ambient Temps Week of 7-16-07
Chicago Ambient Temperatures
Somerset Ambient Temperatures
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All internal monitors - Centerline
Quick cool down and excellent control (low variability)
Looks like a cold room
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External Monitors – Truck surface
Blue Line – Back door of trailer Green Line – Driver side Trailer wall Red Line – Passenger side Trailer wall
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Monitors on Product Pallets
Good airflow – based off loading pattern, no hot/cold spots,
therefore, monitor location not critical
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Internal on the product pallet
Blue Line – Pallet A Green Line – Pallet B
Monitor location not critical
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Monitors on the inside of the trailer walls
External wall temp ~ 100 °F, R value is adequate to insulate vs. conduction
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Middle Monitor between Pallets
Flat line
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Ambient Temps Week of 7-23-07
Chicago Ambient Temperatures
Somerset Ambient Temperatures
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All Monitors 7-23-07 Shipment – Centerline Loading
•Maximum load of 4 ½ product pallets plus Commodities•Loaded with the Centerline loading pattern
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Current Monitor Locations (3 per shipment)
Blue line – Pallet A driver side Red Line – Pallet N, last pallet facing back doors Green Line – Pallet B, facing back doors
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All possible monitoring locations
Warmest location – Pallet M, middle between pallets Coldest location – Pallet D, top
Nice and tight
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External Monitors – truck surface
Blue Line – Back door of trailer Green Line – Driver side Trailer wall Red Line – Passenger side Trailer wall
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Monitors on Product Pallets
Tight
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Monitors on Commodity Pallets
No heat load
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Internal on the product pallet
Blue Line – Pallet A Green Line – Pallet B Red Line – Pallet C Yellow Line – Pallet D Lt Blue Line – Pallet E
Product was at 2-8 °C and stayed at 2-8 °C
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Monitors on the inside of the trailer walls
Airflow and wall R value keeps inside wall temperatures acceptable
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Monitors placed towards the walls
Highest to Lowest Temperature (Maximum Delta of 2°C)Orange Line – Pallet F Aqua Green Line – Pallet M
Monitor facing the wall – potential heat source
4-6 °C = beautiful
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Middle Monitors between Pallets
Highest to Lowest Temperature (Maximum Delta of 4°C) Light Blue Line – Pallet M Dark Blue Line - Pallet A
4-6 °C = beautiful
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Loading Pattern
Criteria Wall Loading Centerline Loading
Impact of Load High Minimal
Hot/cold spots Yes No
Cool down times Lengthy – up to 8 hours Less than 2 hours
Temperature Profile
Wide and Varied Tight and within specifications
Airflow Reduced, making walls heat up and product temperatures
rise
Optimal
Monitor location/quantity
Monitor the hot and cold spots / need 3+ monitors
Location and quantity not critical
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Transport Equipment Guidelines
These documents provide definitions, requirements, test methods, and conformance conditions for the trucking industry.
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Conclusion
1. Loading pattern is critical (airflow is most important)
2. Set point has to be correct
3. DQ, IQ, OQ has already been done per the stds
4. PQ – do this to understand your equipment and loading/transportation process
• Equipment maintenance is critical
5. Post validation monitoring
• 0-1 point based of PQ
6. We did not see a hot or cold spot with proper loading
7. Program and any justification should be part of the VMP
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Questions?