Validation needs for packages of medical devices ......Validation of Packaging Processes...
Transcript of Validation needs for packages of medical devices ......Validation of Packaging Processes...
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Validation needs for packages of medicaldevices – Packaging processes, shelf-life and transportationJan PeetersUL MDTLife & Health
Agenda
Validation needs for packages of medical devices –Packaging processes, shelf-life and transportation
Introduction Validation of Packaging Processes Justification of Shelf Life for Medical Devices & Accessories Transport Safety Summary
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Agenda
Validation needs for packages of medical devices –Packaging processes, shelf-life and transportation
Introduction Validation of Packaging Processes Justification of Shelf Life for Medical Devices & Accessories Transport Safety Summary
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Introduction
? What are the international requirements for packages?
? Which standards must be considered?
? Are the standards also applicable for non-sterile medical devices?
? Terminology within packaging validation studies?
? Which general requirements must be fulfilled by a packaging system?
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Introduction
Packaging Processes and Validation
Good Manufacturing Practices for the manufacture, packing, storage and installation of medical devices, 21 CFR 820.130 Device packaging:
“The device package and any shipping container for a device shall be designed and constructed to protect the device from alteration or damage
during the customary conditions of processing, storage, handling, and distribution.”
FDAMDD
Sterile barrier system
Medical Device
Directive 93/42/EEC and 2007/47/EC (MDD), Essential Requirements:
"The device must be designed, manufactured and packed in such a way that their characteristics and performances during their intended use will not be adversely affected during transport and storage, taking account of
the instruction and information provided by the manufacturer."
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Introduction
ISO 11607 Packaging for terminally sterilized medical devices
Part 1: Requirements for materials, sterile barrier systems and packaging systems
Part 2: Validation requirements for forming, sealing and assembly processes
Both parts (issued in 2006) are amended in 2014
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Introduction
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Protective packaging
Sterile barrier system (SBS)
In the past mixed terms Package Final package Primary package ......
Medical Device
Packaging system
now
Sterile barrier system (SBS) Minimum package that prevents ingress of microorganisms and allows aseptic presentation of the product at the point of use
Protective packaging Configuration of materials designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of use
Packaging system Combination of the sterile barrier system and protective packaging
Introduction
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Requirements of packaging system
• Minimize safety hazards
Maintain sterility
Malfunction
Biological risks
• Allow sterilization
• Allow aseptic presentation
Introduction
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Packaging system performance testing
• Demonstrate integrity of SBS
After sterilization
After handling, distribution and storage
• Worst case packaging process conditions
Introduction
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Stability testing
Demonstrate integrity of SBS over intended shelf-life
Real time aging
Accelerated aging
Agenda
Validation needs for packages of medical devices –Packaging processes, shelf-life and transportation
Introduction Validation of Packaging Processes Justification of Shelf Life Transport Safety Summary
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Validation of Packaging Processes
? Which processes must be validated?
? What is the meaning of IQ, OQ and PQ, and are these relevant for me?
? Is it sufficient to do the validation of my packaging processes only one time (initial validation)?
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Validation of Packaging Processes
Requirement of ISO 11607-2: All packaging processes of sterile barrier systems shall be validated.
Goal: Demonstrate the efficacy and reproducibility of the packaging processes for producing stable sterile barrier systems
Examples of packaging processes rigid and flexible blister forming pouch, reel, or bag forming and sealing form/fill/seal automated processes kit assembly and wrapping assembly of sterile fluid-path products tray/lid sealing filling and closing of reusable containers sterilization sheets folding and wrapping
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Validation of Packaging Processes
Installation Qualification (IQ)
Evaluation: • installation conditions• software validation• environmental conditions• operator training• cleaning and maintenance instruction• …
Critical process parameters: defined and controlled.
Calibrate instrumental parameter, like temperature, pressure and time
Install warning systems or machine stops for critical process parameters
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Validation of Packaging Processes
Operational Qualification (OQ)
Evaluate: Instrumental parameters for e.g. forming, sealing, assembling.
Goal: • Assure that all predefined requirements under all anticipated conditions of
manufacturing are fulfilled. • State the homogeneity of the parameters.• Evaluation of effects at least at the lower and upper parameter limits.
The operational qualification has to be performed for each packaging material and each equipment. No MD needed.
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Validation of Packaging Processes
Performance Qualification (PQ)
• Packaging processes will consistently produce acceptable sterile barrier systems under specified operating conditions.
• Demonstration the variability and reproducibility of the processes• Run three individual production runs, including sterilization, will be evaluated
and compared to the predefined requirements (e.g., appearance, seal width and strength, tightness)
The performance qualification has to be performed for each packaging material and each equipment. MD has to be stored in the SBS.
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Validation of Packaging Processes
Revalidations of Packaging Processes:If changes are made to the equipment, product, packaging materials or packaging process, which compromise the original validation and affect the sterility, safety or efficacy of the sterile medical devices
Examples: Changes of raw material; New equipment pieces; Change of facility or location; Changes in the sterilization process; Negative trends in quality or process control indicators.
It is advisable to consider periodic revalidations since multiple minor changes could cumulatively affect the validation status of the process.
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Agenda
Validation needs for packages of medical devices –Packaging processes, shelf-life and transportation
Introduction Validation of Packaging Processes Justification of Shelf Life Transport Safety Summary
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Justification of Shelf Life
? Which influencing factors must be considered?
? How to correlate accelerated aging and real time aging data?
? What could be an appropriate test design for a combined packaging shelf life validation study?
? Can I use a sterility test to demonstrate the functionality of my packaging system?
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Sterilization
Final use as sterile medical device
Manufacturing and packaging
Transport
Storage
Transport
Justification of Shelf Life
Transport
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Beschleunigte Alterung
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o ISO 11607-1 requires: The stability test has to be carried out using real time aging.o BUT: The stability test using reports on accelerated aging shall be regarded as sufficient evidence
for the expiry date required until data from studies on real time aging are available.
Background
ASTM F1980: Standard Guide for Accelerated Aging of Sterile Medical Device Packages
o Basis for the storage simulation is the Arrhenius equation
o Increase in environmental temperature increases the reaction rate
o Observe the temperature tolerance limits of the ageing materials and the MD! Advice of ASTM F1980: below or at 60 °C
General
Where:AAF: accelerated aging factorTAA: accelerated aging temperature (°C)TRT: ambient temperature (°C)Q10: aging factor; typically 2.0 (conservative approach)
Determination Ageing Factor
Justification of Shelf Life
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Accelerated Aging
10/10
RTAA TTQAAF
Justification of Shelf Life
Sam
plin
g D
ates
Before Sterilization
Baseline - after sterilization
After transport simulation
After accelerated aging
1 Y 3 Y 5 Y After real-time aging
1 Y 3 Y 5 Y
Test
Sys
tem
s
Visual Inspection X X X X X X X X X
Peel Test X X (X) X X X X X X
Dye Test X X (X) X X X X X X
Burst Test X X (X) X X X X X X
Bubble Emission Test X X X X X X X X X
Air Permeability X X (X) X X X X X X
Functional Tests (X) X X X X X X X X
Biocompatibility (X) X (X) X X X X X X
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Samples: Manufacturing under worst case conditions
Example (Test Design UL)
Performance Testing SBS• Integrity SBS
• Physical tests and microbial barrier testing of porous materials can be used to demonstrate the capacity of the SBS to maintain sterility. Preferable use standardized test methods, ISO 11607-1, Annex B.
• No sterility testing unless explicit requested by vertical product standard!
accelerated aging is performed at increased temperature negative impact upon microorganisms
Sterilization requirements: Confirmation SAL 10-6
Packaging system: Typically at least 2 packages covering the device
Justification of Shelf Life
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Shelf life of medical device:o Biocompatibility
o Functionality
o Visual appearance (color changes, breaks or cracks, etc.)
o Potential degradation of the basic materials
o Migration of additives
o Corrosion of metals
Justification of Shelf Life
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Agenda
Validation needs for packages of medical devices –Packaging processes, shelf-life and transportation
Introduction Validation of Packaging Processes Justification of Shelf Life Transport Safety Summary
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Transport Safety
? Are there standards available to use as guidance?
? How can I validate the transportation of my particular product?
? Non-sterile products: Is it necessary to perform a transport validation study?
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Transport Safety
Standards/Guidance documents:o ASTM D4169: Standard Practice for Performance Testing of
Shipping Containers and Systemso ISTA 1, 2 und 3 Series: International Safe Transit Association
Preshipment Test Procedureso ISO 4180-1: Complete, filled transport packages – General rules
for the compilation of performance test schedules – Part 1: General principles
The documents are listed in ISO 11607-1, Annex B, as standardized test methods, that may be used to demonstrate compliance with the requirements of this standard
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Transport Safety
Non-Simulation Integrity TestingPre-testing; to identify the suitability of an intended packaging systemStandard: ISTA Series 1
General Simulation Performance TestsTest design on the basis of standardized test procedures; to simulate the complete transportation chainStandard: ISTA Series 2 and 3, ASTM D4169
Focused SimulationUse of measured data received from a real transportation chainStandard: None
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Transport Safety
Test Modelso Climatic exposureo Compression testingo Vibration testingo Shock testingo Low pressure testingo Concentrated impact testing
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Transport Safety
Test design compression testing
SPONSOR
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Transport Safety
Test design vibration test (4 different orientations)
SPONSOR
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Transport Safety
Test design shock test32
Damages after shock test
Transport Safety
Evaluation: mostly of cosmetic naturePrevention: reinforcement of corners
SPO
NSO
R
Evaluation: Damaging packages or lost of productsPrevention: Use of suitable shipment box!
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Damages after vibration test
Transport Safety
Evaluation: mostly of cosmetic naturePrevention: only using pallet shipment
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Damages after compression test
Transport Safety
Evaluation: May result into product damaging; high riskPrevention: More stable tape, more stable cardboard box, additional filling material
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Damages after shock and/or vibration test
Transport Safety
Result: Breaks within blister, damaging of packaging material by the productEvaluation: Integrity loss of sterile barrier systemProtection: additional filling materials or inlays, protecting packaging, more stable packaging materials
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SPO
NSO
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Transport Safety
Producto Visual inspection, functionality test, tightness testing, etc.o Damages: Breaks, disconnection, leakageo Evaluation: Cosmetic, Loss of functionalityo Prevention: Selection of suitable packaging materials, stabilization of the
product within the package, etc.
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Agenda
Validation needs for packages of medical devices –Packaging processes, shelf-life and transportation
Introduction Validation of Packaging Processes Justification of Shelf Life Transport Safety Summary
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Summary
Important Aspects to Consider:
Use suitable packaging materials Validation of your packaging processes Evaluate the impact of sterilization and transport Justify the intended shelf life for your product
(maintain sterility, biocompatibility and functionality)
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THANK YOU FOR YOUR ATTENTION
Jan PeetersGlobal Program Manager, Scientific Director & Primary Designated Engineer (PDE)
UL MDTmdt medical device testing GmbHGrenzenstrasse 1388416 OchsenhausenGermany
T: 0049 – 7352 – 9114 – 41F: 0049 – 7352 – 9114 – 72E: [email protected]: www.ul-mdt.com