02.10.2014 1 TÜV SÜD Product Service GmbH ASTM meeting Belfast 23-24 September 2014 Notified body perspective: Sterile packaging validation: testing challenges, issues, and mistakes that you see in the industry Dr. Matthias Mondon TÜV SÜD Product Service GmbH Market approval and certification TÜ V Japan Medical Device Safety Testing according to JIS Certification of class II medical devices Audits according to J-GMP requirements China CFDA Registration Europe Conformity assessment procedures according to AIMDD, MDD, IVDD (notified body number 0123) Australia Conformity Assessment Body (CAB) under the current MRA Canada CMDCAS (ISO 13485) CAN/CSA C22.2 NR.601.1 as NRTL USA NRTL Certification FDA 510(k) Third Party Review FDA Third Party Inspections Taiwan Audits according to TGMP requirements under the Taiwanese / European Technical Cooperation Program Brazil Factory Inspections via agreements with INMETRO accredited Certification Bodies Russia Registration Certificate by Roszdravnadzor and declaration of conformity Hong Kong Conformity assessment according to MDACS Singapore CAB for medical devices in Singapore GDPMDS certification Product Safety Testing India Pre-market review according to CLAA Malaysia Conformity Assessment Body (CAB) under the MDA South Korea Technical File Review of class II medical devices CB test reports 2-Oct-14 Healthcare & medical device services
Transcript
02.10.2014
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TÜV SÜD Product Service GmbH
ASTM meeting Belfast23-24 September 2014
Notified body perspective: Sterile packaging validation: testing challenges, issues, and mistakes that you see in the
industryDr. Matthias Mondon
TÜV SÜD Product Service GmbH
Market approval and certification
TÜV
JapanMedical Device Safety Testing according to JISCertification of class II medical devices Audits according to J-GMP requirementsChinaCFDA Registration
EuropeConformity assessment proceduresaccording to AIMDD, MDD, IVDD (notified body number 0123)
AustraliaConformity Assessment Body (CAB) under the current MRA
CanadaCMDCAS (ISO 13485)CAN/CSA C22.2 NR.601.1 as NRTL
USANRTL CertificationFDA 510(k) Third Party ReviewFDA Third Party Inspections
TaiwanAudits according to TGMP requirements under the Taiwanese / European Technical Cooperation Program
BrazilFactory Inspections via agreements with INMETRO accredited Certification Bodies
RussiaRegistration Certificate by Roszdravnadzor and declaration of conformity
Hong KongConformity assessment according to MDACS
SingaporeCAB for medical devices in SingaporeGDPMDS certificationProduct Safety Testing
IndiaPre-market review according to CLAA
MalaysiaConformity Assessment Body (CAB) under the MDA
South KoreaTechnical File Review of class II medical devicesCB test reports
2-Oct-14Healthcare & medical device services
02.10.2014
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TÜV SÜD Product Service GmbH
1 One-stop technical solution provider
800 locations worldwide
employees worldwide 20,190
million Euro in sales revenue 20131,900
150 years of experience
TÜV SÜD Product Services
TÜV SÜD in numbers: Growing from strength to strength
TÜV SÜ
2-Oct-14Healthcare & medical device services
TÜV SÜD Product Service GmbH
Our heritage: 148 years of business success
Establishment of a Mannheim-based steam boiler inspection association by 21 operators and owners of steam boilers, with the objective of protecting man, the environment and property against the risk emanating from a new and largely unknown form of technology
1866
First vehicle periodic technical inspection (PTI)1910
1958 Development of a Bavaria-wide network of vehicle inspection centres in the late 1950s
1926 Introduction of the “TÜV mark / stamp” in Germany
1990s Conglomeration of TÜVs from the southern part of Germany to form TÜV SÜD and the expansion of business operations into Asia
TÜV SÜD pursues a strategy of internationalisation and growth
Today
2006 Expansion of services in ASEAN by acquiring Singapore-based PSB Group
2009 Launch of Turkey-wide vehicle inspection by TÜVTURK
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TÜV SÜD Product Service GmbH
Auditing and system certification services
Quality management§ ISO 13485§ ISO 9001 § ISO 15378
TÜV SÜD: A brand synonymous with quality and safety. Our certification marks and certificates are excellent marketing tools for our customers. Our test reports provide customers with the confidence to market their products’ safety, quality and sustainability attributes.
> 46,000 system certificates
TÜV
> 320,000 product certificates
2-Oct-14Healthcare & medical device services
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TÜV SÜD Product Service GmbH
ASTM meeting Belfast23-24 September 2014
Notified body perspective: Sterile packaging validation: testing challenges, issues, and mistakes that you see in the
industryDr. Matthias Mondon
TÜV SÜD Product Service GmbH
Why Packaging validation?
Ever bought Bananas?
Is something missing?Yes correct, the Packaging!
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TÜV SÜD Product Service GmbH
Why Packaging validation?
Is this all?
We will get back to it
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TÜV SÜD Product Service GmbH
Why Packaging validation?
Also, medical devices must be packed safely!Where does that
requirement come from?
EC-Directive 93/42/EECfor Medical Devices
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Medical Device 93/42 EEC
Dr. Jan Havel
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TÜV SÜD Product Service GmbH
93/42 EEC Article 3: Medical devices, must meet the essential requirements(MDD Annex I).
93/42 EEC Article 11: Compliance to Essential Requiremnts (MDD Annex I) must be demonstrated by a Conformity Assessment Procedure (e.G. Annex II.3).
Medical device 93/42 EEC Annex e.g. II, V
Why Conformity?
TÜV SÜD Product Service GmbH
Contents
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Standard Requirements ISO 11607Documentation• Definition of the
packaging• Validated Methods• Typical Test methods
Directive 93/42/EEC (MDD) Essential Requirements:• 3) The devices must achieve the performances intended by the
manufacturer and be designed, manufactured and packaged in such a way that they are suitable for one or more of the functions referred to in Article 1 (2) (a), as specified by the manufacturer..
• 5) The devices 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 instructions and information provided by the manufacturer.
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TÜV SÜD Product Service GmbH
Regulatory Requirements of the MDD
Directive 93/42/EEC (MDD) Essential Requirements:
• 7.2) The devices must be designed, manufactured and packed in such a way as to minimize the risk posed by contaminants and residues to the persons involved in the transport, storage and use of the devices and to thepatients…
• 8.3) Devices delivered in a sterile state must be designed, manufactured and packed in a non-reusable pack and/or according to appropriate procedures to ensure that they are sterile when placed on the market and remain sterile, under the storage and transport conditions laid down, until the protective packaging is damaged or opened.
• 8.1) The design must allow easy handling and, where necessary, minimize contamination of the device by the patient or vice versa during use
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TÜV SÜD Product Service GmbH
Regulatory Requirements of the MDD
Directive 93/42/EEC (MDD) Essential Requirements:
• 8.4) Devices delivered in a sterile state must have been manufactured andsterilized by an appropriate, validated method (8.4)
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TÜV SÜD Product Service GmbH
Validation
Requirements according to 7.5.2 of EN ISO 13485:2003
• The organization shall validate any processes for production and service provision where the output cannot be verified by subsequent monitoring or measurement.
• Harmonized standard for packaging validation:– EN ISO 11607-1– EN ISO 11607-2
• Harmonised standards refering to packaging validation– EN ISO 13485 Quality Management System– EN ISO 14937 Sterilization of medical devices– EN ISO 17664 reprocessing of medical devices
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EN ISO 17664 3.9 3.11 EN ISO 14937 E.4.3Dr. Jan Havel
TÜV SÜD Product Service GmbH
Responsibility for purchased Items
• The requirements on materials referenced shall apply to those used in preformed sterile barrier systems, as well as sterile barrier systems (Are the pre-shaped sealing-seams appropriate and compatible with the own production process and the own storage conditions?)
Prefabricated packages are not assessed and documented
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ISO 11607-1:2009 5.1.1
What do I do if What do I do if the package is prefabricated?
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TÜV SÜD Product Service GmbH
Contents
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Standard Requirements ISO 11607Documentation• Definition of the
packaging• Validated Methods• Typical Test methods
7.1 The following information shall be provided with the material, preformed sterile barrier system or sterile barrier system:
• - the type, size or grade;
3 Terms and definitions3.9 packaging material
any material used in the fabrication or sealing of a packaging system3.10 packaging system
combination of the sterile barrier system and protective packaging3.13 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
3.22 sterile barrier systemminimum package that prevents ingress of microorganisms and allows aseptic presentation of the product at the point of use
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TÜV SÜD Product Service GmbH
Why Packaging validation?
Is this all?
No!
There is also a bag, a cartonbox and perhaps anotherwrap
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TÜV SÜD Product Service GmbH
Documentation Requirements ASTM D 4169
• 5. Test Specimen• 5.1 Test specimens consist of representative samples of
complete shipping units, including actual contents.• 3. Terminology: • 3.2.7 shipping unit—the smallest complete unit that will be
subjected to the distribution environment, for example, a shipping container and its contents.
Definition of the packaging and the device is essentiale.g. actual contents also include desiccant pouches, SBS carton pieces for protection, Tyvek pieces for protection,
which need to be defined.
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TÜV SÜD Product Service GmbH
Contents
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Standard Requirements ISO 11607Documentation• Definition of the
packaging• Validated Methods• Typical Test methods
The test method validation shall demonstrate the suitability of the method including:
• a rationale for the selection of the appropriate tests for the packaging system
• the establishment of acceptance criteria; repeatability; reproducibility;
• and sensitivity for integrity tests
• Sampling plans shall be based upon statistically valid rationale.(e.g. ISO 2859-1, ISO 186)
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ISO 11607-1:2009 4.3; 4.4.2/3Dr. Jan Havel
TÜV SÜD Product Service GmbH
Rationale of test-methods
• We perform our packaging validations according:
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accelerated aging ASTM F1980biocompatibility ISO 10993-1integrity ASTM F1929microbial barrier DIN 58953-6Peel-open characteristic EN868-5Performance testing ASTM D4169Seal strength EN 868-5Visual inspection ASTM F1886
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TÜV SÜD Product Service GmbH
Performance requirements for sterile packaging
Packaging validations must consider the following aspects :
• Integrity of the sterile barrier system shall be demonstrated after sterilization and subsequent performance testing (6.3.1)
• Performance testing shall be conducted on the "worst case“ packaging system produced at the specified process limits of forming and sealing (including sterilization effects) (6.1.6/6.3.4) (storage and transport (6.3.5))
• packaging stability /integrity of the product lifecycle (6.4) (physical protection 6.1.2, microbial barrier properties 5.2, presentation in aseptic manner 6.2.2) has to be established.
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ISO 11607-1:2009 6.1.1;6.1.2;6.1.4;6.1.4;6.2.2;6.3.1;6.3.4;6.3.5;6.4.7Dr. Jan Havel
TÜV SÜD Product Service GmbH
Selection of appropriate test methods
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Mikrobial barrier properties
Life cycle
Seal strength
Aseptic presentation
Performance evaluation over the planned life cycle
What do I proof, and how?
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TÜV SÜD Product Service GmbH
Selection of appropriate test methods
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Visual inspection is not suitable to be the sole test
method!
Dr. Jan Havel
TÜV SÜD Product Service GmbH
The logic connection – an example:
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Life-cycle
Asepticalpresentation
Mikrobial Barrier
accelerated agingbiocompatibility ISO 10993-1integritymicrobial barrier DIN 58953-6Peel-open characteristicPerformance testingSeal strengthVisual inspection
ASTM F1980; EN 868-8
ASTM F1929; ASTM F2227
ASTM D4169; ISTA1,2,3; EN 868-8 EN 868-5; ASTM F 88; ASTM F 2054; ASTM F 1140
ASTM F1886; EN 868-8
Dr. Jan Havel
ASTM F1886
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TÜV SÜD Product Service GmbH
Validation-plan
• The validation plan should reflect the rationale for the packaging test:– Is the order for the test sequences logical?– For which statements regarding packing characteristics was
by what standard (state of the art) investigated?– Are the acceptance criteria logical for the corresponding type
of packaging? (E.g. permeability)• Material• Sterilization method• fixation in the packaging system
– Are all the parameters tested based on a risk assessment
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TÜV SÜD Product Service GmbH
Justification of sample size
• Based on the risk assessment in risk management
– In case of a risk reduction of 10X for In-sterility due to a specific packaging problem.
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What process safety is necessary to verify the Risk control measure?
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TÜV SÜD Product Service GmbH
Justification of sample size ASTM D4169:
• 5.3 The number of test replications depends on the desired objectives of the testing and the availability of duplicate products and shipping containers. Replicate testing is recommended to improve the reliability of the test results.
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TÜV SÜD Product Service GmbH
Contents
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Standard Requirements ISO 11607Documentation• Definition of the
packaging• Validated Methods• Typical Test methods
• Insufficient statistical sound sample sizes at packaging PQ (3 samples tested) – no risk based approach.
• No justification on the applied test methods – only standards stated.
• Assumption that methods from standards are generally valid. Missing evidence of test method validation. (e.g. other dyes in dye penetration test)
• Packaging PQ not performed by 3 runs covering process tolerances.
• OQ not investigated on both – upper and lower sealing tolerance to justify worst case decision for PQ.
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TÜV SÜD Product Service GmbH
Typical failures in validation protocols
• Seal strength testing without considering aseptic presentation state of the art or rational for deviation.
• Equipment not validated at the manufacturing place/position• PQ not performed with different lots of raw material. Failure of
new material Lot under routine conditions due to material variation.
• No independent acceptance criteria for peel force but related to the machine
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TÜV SÜD Product Service GmbH
Typical failures in validation protocols
• Packaging performance testing:
– Transport simulation not checked by integrity testing of the
sterile barrier
– No standard followed; the tests are not validated
(sending the product back and forth to an affiliate is not
standardized and validated.)
– Accelerated aging insufficient due to calculation problems.
– Wrong storage temperature assumed.
– Missing integrity or seal strength testing after shelf life.
– Poor traceability of the packaging lots used for validation.02.10.2014 48Dr. Jan Havel
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TÜV SÜD Product Service GmbH
Typical failures in validation protocols
• Assumptions that preformed sterile barrier systems are in
compliance without further testing.
• Supplier not certified to EN ISO 13485.
• Missing evidence of process validation.
• Not all parts of the EN ISO 11607-1 and -2 are addressed
(check for each requirement – TUEV SUED has a checklist
available to be bought but everyone can read the standard)
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TÜV SÜD Product Service GmbH
Summary: Validation protocol - logical contents
• What is the product?– How does the product look like, what is the packaging system like?– Who are the suppliers, what are the packaging system materials?– Where will be delivered and what is the product life cycle?
• What is the Process?– What are the routine manufacturing steps (Parameter of packaging,
Parameter of Sealing machines)– Is the packing plant and the laboratory equipped with an appropriate
quality management system to guarantee validated processes?• Validation rationale
– What is the worst case for the packaging process and packaging (Performance testing, including traceability to lot numbers)
– Sample size, detection methods, test tolerances– Description and justification of deviations (in the report)
