European packaging regulations

March 3-5, 2009www.healthpack.net

European Packaging RegulationsWhat to expect from a notified body audit of

your packaging

Dr. Ralf WaltherTÜV Süd Product Service GmbH

European Packaging Regulations - R. Walther

Content

1. Short introduction of TÜV Süd Product Service

2. The European Medical Device Directive3. Harmonized Standards and their role in

the European medical device regulation4. Typical observations during audits and

design dossier review5. Final remarks

European Packaging Regulations - R. Walther 3

The Company TÜV Süd

Technical service providerMore than 13.000 employeesMore than 600 sites worldwideturnover 2007: 1.269 Mio. EuroMain offices: Munich, Danvers, Singaporesuccessful in the market since more than 140 years

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


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


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


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.


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


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


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 allrequirements (not only to those referenced in Annex ZA)


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


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)


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


Parts 1 and 24.3 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.



Requirement: Rational for selection of method

Observation: No data provided

Comment : --



• 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: --


Seal strength testingpaper – paper pouch


Seal strength testingpaper – paper pouch


Seal strength testingpaper – film pouch


Seal strength testingpaper – film pouches



• Requirement: Sensitivity for integrity test

• Observation: Not performed or no data provided

• Comment: --


Parts 1and 24.3 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


Part 15.1.4 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


Part 15.2 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


Part 15.3 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


Part 16.3 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


Part 16.4 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


Part 25.1.4 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


Part 25.1 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


Part 25.2 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



• 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



• 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


Part 25.3 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


Part 25.3 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


Part 25.4 Performance Qualification

• Requirement: Process repeatability and reproducibility

• Observation: No criteria defined or no justification given for acceptance criteria

• Comment: --



• 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!


Part 25. 4 Performance Qualification

• Requirement: The process shall be under control and capable

• Observation: No statistical data provided that demonstrate a capable process



• 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.


Part 25.7 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


Part 2Use 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)


Part 2Purchasing 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


Packaging in Design Dossiers

The following should be mandatory 1. Package material specifications2. Specification of the packaging system (sterile

barrier + protective packaging)3. Process validation for manufacturing of the

sterile barrier4. Stability data, at least plan + initial data5. Validation plan and report for final pack


Additional Guidance Document

• Guidance document for validation of sealing process published by „Deutsche Gesellschaft für Sterilgutversorgung“, ZLG and TÜV RheinlandGmbH (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.


Further reading

For general information about the European approach and web links:

• See AAMI TIR 22:2007 Annex A.3

Healthcare

European packaging regulations