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


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


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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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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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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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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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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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.

17Packaging Processes and Validation

Agenda



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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


Transport

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Beschleunigte Alterung

The image part with relationship ID rId4 was not found in the file.

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


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Accelerated Aging

10/10

RTAA TTQAAF


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


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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


24Packaging Processes and Validation

Agenda



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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

R

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



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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

validation needs for packages of medical devices ......validation of packaging processes...

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