What to expect from a notified body audit of your packaging Dr. Ralf Walther TÜV Süd Product Service GmbH March 3-5, 2009 www.healthpack.net
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
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 3
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 all requirements (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 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.
Parts 1 and 2 4.3 Test Method Validation Requirement: Rational for selection of method Observation: No data provided Comment : --
Requirement: Parts 1 and 2 4.3 Test Method Validation 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 testing paper paper pouch
Seal strength testing paper paper pouch
Seal strength testing paper film pouch
Seal strength testing paper film pouches
Parts 1 and 2 4.3 Test Method Validation Requirement: Sensitivity for integrity test Observation: Not performed or no data provided Comment: --
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
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
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
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
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
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
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
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
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
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
Requirement: Software validation Part 2 5.2 Installation Qualification 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 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
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
Part 2 5.4 Performance Qualification Requirement: Process repeatability and reproducibility Observation: No criteria defined or no justification given for acceptance criteria Comment: --
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!
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
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.
Comment: Part 2 5.7 Changes and Revalidation 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 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)
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
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
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.
Further reading For general information about the European approach and web links: See AAMI TIR 22:2007 Annex A.3