2. European Packaging Regulations
- R. Walther
Content
1. Short introduction of TÜV Süd Product
Service
2. The European Medical Device Directive
3. Harmonized Standards and their role in
the European medical device regulation
4. Typical observations during audits and
design dossier review
5. Final remarks
3. European Packaging Regulations
- R. Walther 3
The Company TÜV Süd
Technical service provider
More than 13.000 employees
More than 600 sites worldwide
turnover 2007: 1.269 Mio. Euro
Main offices: Munich, Danvers,
Singapore
successful in the market since more
than 140 years
4. TÜV Süd Product Service GmbH
- is a subsidiary of TÜV Süd
- is the Notified Body with the majority of
class III certificates for Medical Devices
- has branch offices in many European
countries, North America and Asia
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- R. Walther
The European
Medical Device Directive
Correct title: Council Directive 93/42/EEC of 14 June 1993
concerning medical devices
• Annex I defines the requirements for products and
packages.
• They are very general in the description of the
requirements and address safety aspects to be met
including
– Design
– Manufacturing
– Transport
– Storage
– Prevention of infections
– Labelling
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The European
Medical Device Directive
Anx. I, 8.4. Devices delivered in a sterile
state must have been manufactured and
sterilized by an appropriate, validated
method
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Harmonized Standards
• Article 5 of the MDD makes reference to
the Harmonized Standards.
• Presumption of conformity in case the
standard is followed.
• They are published in the Official Journal
of the European Community.
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Harmonized Standard
• The European foreword of a harmonized
standard gives or may give additional
information on the use the standard
• Annex ZA references the sections of the
standard to the Essential Requirements of
the MDD that will be fulfilled
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Reference EN ISO 11607-2 and MDD
4.1 1, 2
4.2, 4.3, 4.4 3, 4, 5, 6
5.1 to 5.7 7.1, 7.5, 7.6, 8.1, 8.5
6.1 8.5
6.3 8.6
7 1, 2, 6, 8.5, 8.6
8.1, 8.2 7.1, 7.5, 7.6, 8.1
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Harmonized Standards
• The use of standards – including harmonized
standards – is voluntary!
• In case you decide not to refer to the standards
you have to demonstrate that the same level of
safety is achieved by your solution
• In case you claim compliance with a harmonized
standard you have to comply with all
requirements (not only to those referenced in
Annex ZA)
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Notified Bodies and
Packaging Assessment
• There are several Notified Bodies and they
may not necessarily use the same
interpretations. Harmonization may be
expected but is still not very likely
• Within one Notified Body you may also
expect differences in interpretation
between auditors
• Beside audits experts also review design
dossiers including packaging
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General comment
Auditors expectations:
• Risk analysis shall be available
• Is not a requirement specific for packaging
• Is based on a requirement of ISO 13485
sect. 7.1 (…shall establish documented
requirements for risk management throughout
product realization)
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Parts 1 and 2:
4.2 Sampling
• Requirement:
Sampling plans based on statistically valid
rational
• Observation:
No information provided
• Comment:
Typical applications for big lots, small lots or
infrequent process (e.g. closure of preformed
sterile barrier system e.g. pouches or rolls)
usually require different approaches
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Parts 1 and 2
4.3 Test Method Validation
• Requirement:
Methods shall be validated
• Observation:
No validation preformed or no data provided.
Historical data used for demonstration of
performance
• Comment :
Test methods described in standards or not
described in standards may need a different
extend in validation. In house testing is
acceptable.
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Parts 1 and 2
4.3 Test Method Validation
Requirement:
Rational for selection of method
Observation:
No data provided
Comment : --
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Parts 1 and 2
4.3 Test Method Validation
• Requirement:
Assessment of method for repeatability and
reproducibility
• Observation:
In depth knowledge of test method not always
obvious, e.g. interpretation of underlying data
not clear, no information about software used.
• Comment: --
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Parts 1 and 2
4.3 Test Method Validation
• Requirement:
Sensitivity for integrity test
• Observation:
Not performed or no data provided
• Comment: --
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Parts 1and 2
4.3 Test Method Validation
• Requirement:
Conditioning of samples
• Observation:
No conditioning of samples, no rational for not
performing conditioning
• Comment:
Not all tests / materials may require conditioning,
provide short rational if not applicable
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Part 1
5.1.4 General Requirements
• Requirement:
Consideration of tests, e.g. bioburden
• Observation:
No bioburden testing for packaging materials
• Comment:
Regular testing depends on product and/or
sterilization method
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Part 1
5.2 Microbial Barrier
• Requirement:
Porous material shall provide an adequate
barrier to microorganisms
• Observation:
No data provided
• Comment:
No generally accepted test method; supplier of
material shall certify microbial barrier property
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Part 1
5.3 Compatibility with the sterilization process
• Requirement:
Material must be compatible with sterilization
process (microbial barrier, biocompatibility)
• Observation:
No or insufficient data provided
• Comment:
Usually this information is provided by the
supplier of the packaging materials
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Part 1
6.3 Packaging system performance testing
• Requirement:
Use sterilized products/packages, preferable
standardized methods
• Observation:
No or insufficient data provided
• Comment:
It is recommendable to use AAMI TIR 22 for
guidance
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Part 1
6.4 Stability testing
• Requirement:
Accelerated aging and real time shelf life shall
begin simultaneously
• Observation:
Not followed
• Comment:
May be difficult to achieve. It is essential that
samples for real time shelf life cover possible
influences of the packaging and the sterilization
process
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Part 2
5.1.4 General
• Requirement:
Development is not a part of validation
• Comment:
Clear separation recommended to make sure
that the criteria are met within planned scope of
the protocol
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Part 2
5.1 General
• Requirement:
Validation using data of existing products
• Observation:
Insufficient rational provide (esp. in design
dossiers)
• Comment:
Usually only IQ and / or OQ data may be used
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Part 2
5.2 Installation Qualification
• Requirement:
Definition of critical parameters
• Observation:
Risk management is not used for identification of
critical parameters
• Comment:
Risk management not always properly
integrated into validation and CAPA
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Part 2
5.2 Installation Qualification
• Requirements:
Calibration of sensors and gauges before and
after validation
• Observation:
No calibration before and after validation
• Comment:
Acceptance of single calibration of test
equipment possible, rational required
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Part 2
5.2 Installation Qualification
• Requirement:
Software validation
• Observation:
Incomplete or difficult to trace back
• Comment:
Includes as a minimum the controller of the
packaging machine; software of test
instrument(s) if applicable
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Part 2
5.3 Operational Qualification
• Requirement:
All anticipated conditions for manufacturing
• Observation:
It is not precisely described and assessed if
such investigations are performed; data are
insufficient to demonstrate compliance
• Comment:
It is recommended to address this in protocol
and report
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Part 2
5.3 Operational Qualification
• Requirement:
Selection of worst case conditions = upper and
lower limits for process parameters and their
combination(s)
• Observation: --
• Comment:
Identification of worst case conditions should /
could be referenced to process analysis in order
to understand process inputs; description for
selection of parameters helpful
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Part 2
5.4 Performance Qualification
• Requirement:
Process repeatability and reproducibility
• Observation:
No criteria defined or no justification given for
acceptance criteria
• Comment: --
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Part 2
5.4 Performance Qualification
• Requirement:
3 production runs with adequate sampling;
duration should account for process variables
• Observation:
No explanation given for selection of conditions
used
• Comment:
What is defined to be “a run”? Which variations
have to be considered (e.g. materials, brakes,
clearance of process disturbance, personnel
change?) See also 4.2 for statistics!
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Part 2
5. 4 Performance Qualification
• Requirement:
The process shall be under control and capable
• Observation:
No statistical data provided that demonstrate a
capable process
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Part 2
5.7 Performance Qualification
• Comment:
Definition of process capability index or other
process performance figure that demonstrates
compliance. The index or figure shall be related
to anticipated risks for the patient in case of non
compliance.
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Part 2
5.7 Changes and Revalidation
• Comment:
– Rational for extent of revalidation required.
– Assessment of impact of change on validated
process
– Planning of validation measures incl.
acceptance criteria, performance and final
evaluation of change
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Part 2
Use of preformed sterile barrier
• Process:
Use of preformed sterile barriers e.g. use of
pouches that are only closed at the bottom seal
(usually non peelable) or rolls
• Comment:
Confirmation by supplier that requirements of
ISO 11607 part 1 and 2 are met (should include
process validation)
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Part 2
Purchasing Control
• Process:
Interface between manufacturer of the device
and supplier of packaging material(s)
• Comment:
– Purchasing control required
– Certificate for compliance with ISO 13485
strongly recommended
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Packaging in Design Dossiers
The following should be mandatory
1. Package material specifications
2. Specification of the packaging system (sterile
barrier + protective packaging)
3. Process validation for manufacturing of the
sterile barrier
4. Stability data, at least plan + initial data
5. Validation plan and report for final pack
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Additional Guidance Document
• Guidance document for validation of sealing
process published by „Deutsche Gesellschaft für
Sterilgutversorgung“, ZLG and TÜV Rheinland
GmbH (version 1 dated July 2008).
• Only available in German language.
• Is supposed to support hospitals but also may
be used by other organizations using this type of
process.
• The authors do not guarantee completeness of
implementation of the ISO 11607-2.
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Further reading
For general information about the European
approach and web links:
• See AAMI TIR 22:2007 Annex A.3
