IoPP Education Track ConferenceMedical Device Packaging Designfrom a Designer’s Perspective

Pack Expo: Chicago, IL November 3, 2010

Jan Gates, Abbott Vascular Temecula, CAKaren Greene, Life Packaging Technology LLC Carlsbad, CA

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MDPTC: Mission Statement

• Provide a forum for packaging professionals representing the Medical Device Industry for discussion, exchange and development of information on issues that affect them in areas of organization, problems and technical issues, regulations, standards and new technologies.

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MDPTC: Vision Statement

• Provide the latest information on national and international regulatory requirements as they affect the packaging of medical devices.

• Provide a forum to voice the device industry packaging position on issues that affect them.

• Provide education to new members entering the medical device area of package engineering.

• Provide a timely list of tools and documents (guides, test methods and standards) that are helpful when performing the tasks related to the package engineering of medical devices.

• Exchange non- proprietary information regarding new materials, equipment and systems, which can improve the overall performance and quality of the medical device packaging industry.

• Act as a liaison for technical and regulatory updates between organizations of mutual interest such as AAMI, ISO, ASTM, ISTA and the U.S. FDA.

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MDPTC: Subcommittees• Labeling

– Dave Olson – AdvancedWeb

• Industry Standards & Regulatory Liaison– Hal Miller, Pace LLC / Alison Tyler, Beacon Converters

• Education– Jennifer Neid Benolken/Jennifer Blocher, Sealed Air Medical

• ESD – Robert Vermillion, RMV Technology Group LLC

• Sustainability– Daphne Allen, Pharmaceutical and Medical Packaging News

• Sterilization– Michael Tokarski, KCI Medical

• Combination Products– Jim Butschli, Health Care Packaging

• Industry Benchmarking - inactive– Curt Larsen, Spartan Design

• Materials Specifications - inactive– Nick Fotis, Cardinal Healthcare

Agenda

• Introductions

• Medical device packaging examples

• Regulatory Framework for Medical Device Packaging

• The Compliance Sweet Spot:

– Integrating global regulatory compliance for the delivery of a safe and effective medical device with the business imperatives of “time to market”, cost constraints and happy clinician-customers.

• Typical Project Time Frame

• Wrap Up -- Compliance Sweet Spot5

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Regulatory Framework

• Lack of a comprehensive package design process often results in downstream packaging issues

• To assure adequate packaging start with the regulations– ISO 11607 -1: Packaging for terminally sterilized medical

devices — Part 1: Requirements for materials, sterile barrier systems and packaging systems (2007)

– ISO 11607 -2: Packaging for terminally sterilized medical devices — Part 2: Validation requirements for forming, sealing and assembly processes (2007)

– FDA regulatory requirements for your device, http://www.fda.gov/cdrh/devadvice/overview.html

– FDA Quality system regulation for medical devices• CFR Part 820 (21 CFR 820)

• Patient Safety• Other

– Sterility

– Ease of use

– Manufacturability

– Shipping

– Storage

– Cost

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Primary Concern

Seal Breach/Defects

The balance point between safety and efficacy for the patient, regulatory compliance, and costs

A Twelve Step Approach…

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The Compliance Sweet Spot™

Quality Systems• ANSI/AAMI/EN/ISO 11607 -1 & -2 performed within a

formal quality system.• FDA Quality system regulation for medical devices

– CFR Part 820 (21 CFR 820)http://www.fda.gov/cdrh/devadvice/overview.html

– Design control required– Risk management required– Test methods validated– Sampling plans for package testing

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Essential #1

ISO 11607-1

• Package Design Goal

– allow sterilization

– provide physical protection

– maintain sterility up to the point of use

– allow aseptic presentation

• Over 96 ‘shall’ statements in the document

ISO 11607-2

• Packaging system production process:

– Equipment • Development of validated packaging

specification(s) and multiple manufacturing sites/equipment

• Machine specific parts

– Processes validated– Approximately 60 ‘shall’ statements in the document

Compliance Guidance

• AAMI TIR 22 – Guidance document for compliance to ISO11607 -1 & -2

• AAMI TIR 22 may be ISO 11607-3 next year

• Also:

– Read specific device ISO requirements

– Discuss requirements with Regulatory specialists

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Design Inputs• Examples:

– Product attributes– Device protection requirements– Storage, distribution, and handling requirements– Manufacturing requirements– Sterilization process requirements– Marketing requirements– Budget requirements– Customer requirements– Regulatory requirements

Essential #2

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Distribution, Storage and Handling– Anticipated distribution, storage and handling

conditions

– Clinical trial packaging, focus attention: normal to have unusual storage and handling conditions

– Environmental monitoring studies may be required for shipping and storage

– Consult with Logistics, Sales, and Supply Chain team members

Essential #3

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Distribution Hazards

Handling: Shipping and customer drops causing

breakage

Temperature variations

Truck and plane shock and vibration

Distribution Mapping

Pack for sterilization Unload truckShip to hubLoad truckTransfer/sorting hub

FlyStack in tarmacLoad plane

Ship to airport Unload truckLoad truck

Unload planeStack in tarmac

Unload truck

Load truckShip to customer

Customer unloads shipper Prep product for use

Use

Note: 82oC have been measuredNote: -15oC measured,

10 to 300 Hz

Note: 1 to 200 Hz vibrationNote:Over 150 g drops measured

Note: Some 82oC measured

Summary: Many drops, temperature

extremes and vibration points seen

with distribution mapping.

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Selection and Evaluation of Materials and Sterilization Compatibility

– Sterilization compatibility

– Appropriate for equipment

– Appropriate for product

– Biocompatibility

– Aging effects

– Historical use

Essential #4

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• Device sterilization defines package sterilization method.

• Packaging converters– Sterilized material performance data often available

– Biocompatibility, cytotoxicity, and leachables often available

• Traceability document on materials

• AAMI TIR 17:2008 Compatibility of materials subject to sterilization

Material Information

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Shelf Life and Stability Testing• Real time aging required

• Accelerated aging acceptable for commercial release until real time aging is available

• Must use complete packaging system with traceability for all packaging processes, components, and sterilization

− Can use simulated devices or empty packages; focus is on material integrity and seal integrity

− ASTM F1980-07 “Accelerated Aging For Sterile Barrier Systems” presents improved guidance on humidity use.

Essential #5

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ISO 11607-1 document (Section 6.4 NOTE) says:

• Stability testing and performance testing are separate entities

• Performance testing evaluates the interaction between the packaging system and the products in response to the stresses imposed by the manufacturing and sterilization processes and the handling, storage and shipping environment

Stability Testing

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• Understand temperature and humidity effects on materials use, prior to initiating the aging study

• Arrhenius equation (from ASTM F1980)

• Q10 factor understand

• Room Temperature 20º to 25º C

Stability Testing

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Package Design Elements• Design control and documentation• Aseptic presentation, single or double barrier• NO compound folding • Design for manufacturability• Leverage existing designs• Product requirements – design to meet product

fragilities• Investigate product modifications or package design

changes to mitigate failure modes• Labeling Plan—content, CE mark, manufacturing

plan, materials selection and performance

Essential #6

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Prototype the Package Design• KEY STEP TO PACKAGE DESIGN SUCCESS

• Produce prototype for internal design approval and product testing … DOCUMENT the review process

• Iterate, as required

• Low volume production for package system feasibility testing

• Worst case sterilization cycle feasibility testing

• Conduct performance feasibility testing

Essential #7

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Packaging Process Evaluation• Clinical trial or full scale production?• In-house or contract packager?• Buy capital equipment?

– Lead times normally long– Sealers, tooling, vacuum, gas flush, form\fill\seal

• Quality Plans• Manufacturing plan• Labeling manufacturing plan• Packaging equipment and process qualifications

- IQ/EOQ/OQ/PQ• Staff availability and training plan

Essential #8

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Packaging Equipment• Installation qualification (IQ) demonstrates requirements:

– Utilities properly hooked up and meet manufacturer’s requirements

– Equipment features and functions match manufacturer’s bill of materials or purchase order

– Performed every time equipment is moved– Critical operating functions are calibrated accurately– Alarms and limit switches are challenged– Manual specifications match equipment features and

functions operation– Software validated for systems

Essential #9

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Packaging Equipment• Equipment Operational qualification (EOQ)

demonstrates:– Manual specifications match equipment features and

features are operational– Assure operational efficiency over manufacturer's

stated ranges for specified production attributes– Keep the process development and process

qualification activities separate from the equipment operational qualification

Essential #9, continued

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Packaging Production Process Development • Packaging Process Operational qualification (OQ)

demonstrates that:– Worst case packaging material process operating

conditions are established—Design of Experiments

– Sterile barrier systems produced at operating extremes shall meet predefined acceptance criteria

• Formed package (Form, Fill, Seal): correct dimensions

• Sealed packages: intact seals, channels, punctures, tears

• Distribution conditioning – performance testing

Essential #10

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Process Qualification, PQ• Packaging Production Process qualification (PQ)

demonstrates that:

– Process will consistently produce acceptable sterile barrier systems under specific operating conditions• Includes actual or simulated devices• Requires a minimum of three production lot runs at normal

operating conditions (process parameters); consecutive runs are suggested

• Process parameters established during the OQ• Assurance of process control and capability• Process repeatability and reproducibility• Verification of product/package requirements

Essential #11

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Final Packaging Systems Design Validation• Packages must be from a validated process• Product or simulated product, including labeling, to be used• Worst case systems and conditions to be used• Accelerated and real time aging to start at same time• Validated test methods used with rationale• Sampling plans and the statistical rationale built upon high

degree of confidence and reliability• Acceptance criteria: related to sterile barrier integrity and seal

strength as well as device functionality − Criteria based on corporate risk policy

Essential #12

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Performance TestingASTM D4169 ASTM D7386 ISTA 3A

# Cycle 13 TS-4 Standard

1 Handling: ASTM 5276

5 drops at 24”; 1 drop at 48”

4 drops at 20” and 2 drops at 26”

8 drops at 18” and 1 drop at 36”

2 Compression: ASTM D642 Schedule C: 3 sec hold

3 Vibration ASTM D999 (Loose Load/Repetitive Shock)

60 minutes at 1 g and 6 Hz, 3 axis

4 Vehicle vibration: ASTM D4728 (random vibration)

Schedule E: Truck: 0.52 Grms3 hours, 3 axis

2 hours at 0.53 Grms, 2 hours, 3 axis with load

With and without top load, 0.53 Grms 120 minutes, 3 axis and0.46 Grms, 30 minutes, 1 axis

5 High altitude testing: ASTM D6653, where applicable 14000 ft for 1 hour

14000 ft for 1 hour;Random vibration

1.05 Grms (if possible)

6 Handling: ASTM 5276 Schedule A: 5 drops at 24” & one drop at 48” 4 drops at 14” and 2 drops at 20”

7 drops at 18” and 1 drop (next to last) at 36”

7 Vehicle vibration: ASTM D4728 (random vibration) 1 hour at 0.46 g, 2 axis

8 Handling: ASTM 5276 2 drops at 20”, and 3 drops at 26”, and one drop at 38”

9 Concentrated Impact: ASTM D6344 36 inches

Typical Packaging Project Activities Time Frame

How much time does all this take?

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Time Frames

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Design Inputs

4 weeks

Selection and

Evaluation of MaterialsTesting

12 weeks

Packaging System

Development12 weeks

Packaging Process

Evaluation-equipment,

costs, resources—total

process4 weeks

Sterile Barrier System-

FeasibilityTesting

Performance Evaluation12 weeks

Validation—SB System

Manufacturing Process12 weeks

Validation—Packaging

System DesignTesting5 weeks

•Volumes•Equipment•Capital Req.

•Total Costs•Prototype or Trial Runs

•SB System Design Testing

•SB System Test Plan Development (worst case)

•Shelf Life Studies--commence

•Packaging Equipment -IQ, OQ

•Packaging equipment /materials -OQ\PQ

•Formal approval of packaging process validation

•Validation Protocol-consider worst case conditions for design, processing, mfg

•Pkg System Specs•Pkg System Units manufactured by a validated process

•Pkg System sterilized in validated process

•Pkg System contain device or facsimile, IFU’s, all pkg layers or components

•Device protection

•Sterilization process

•Distribution, handling, use

Medical Device Packaging Design

•Steril. Req.•Barrier Req.•Appearance Req.

•Durability Req.•Heat Sealability •Processing Req.•Printing Req.•Cleanliness, Particulates

•Device-Pkg Interaction

•Design Sterile Barrier System

•Design Protective Packaging System

•Labeling Scheme

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The Compliance Sweet Spot

The balance point between safety and efficacy for the patient, regulatory compliance, and costs

A thorough package compliance program is a competitive advantage

The Compliance Sweet Spot – Wrap Up

Patient safety and efficiency

CostsRegulations

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Thank You

Questions??

Medical Device Packaging Design

ReferencesWorks Cited

• Darley, Russell. "Boxing Clever with Packaging." Medical Device Developments 2010. Web. <http://www.medicaldevice-network.com/features/feature90262/>.

• "ASTM D4169 -09 Standard Practice for Performance Testing of Shipping Containers and Systems." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D4169.htm>.

• "ASTM D4728 -06 Standard Test Method for Random Vibration Testing of Shipping Containers." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D4728.htm>.

• "ASTM D5276 -98(2009) Standard Test Method for Drop Test of Loaded Containers by Free Fall." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D5276.htm>.

• "ASTM D6344 -04(2009) Standard Test Method for Concentrated Impacts to Transport Packages." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D6344.htm>.

ReferencesWorks Cited

• ISO 11607, Packaging for Terminally Sterilized Medical Devices, Parts 1 and 2. 2006th ed. AAMI, 2006.

• "Medical Devices." U S Food and Drug Administration Home Page. 07 June 2009 <http://www.fda.gov/MedicalDevices/default.htm>.

• TIR 22, Guidance For ANSI/AAMI/ISO 11607, Packaging for Terminally Sterilized Medical Devices, Part 1 and Part 2:2006. Tech. no. TIR 22. AAMI.

• "ASTM D642 -00(2010) Standard Test Method for Determining Compressive Resistance of Shipping Containers, Components, and Unit Loads." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D642.htm>.

• "ASTM D6653 -01(2006) Standard Test Methods for Determining the Effects of High Altitude on Packaging Systems by Vacuum Method." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D6653.htm>.

• "ASTM D999 -08 Standard Test Methods for Vibration Testing of Shipping Containers." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D999.htm>.

ReferencesWorks Cited

• "ASTM D5276 -98(2009) Standard Test Method for Drop Test of Loaded Containers by Free Fall." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D5276.htm>.

• "ASTM D6344 -04(2009) Standard Test Method for Concentrated Impacts to Transport Packages." ASTM International - Standards Worldwide. Web. 19 Oct. 2010. <http://www.astm.org/Standards/D6344.htm>.

• "Procedures." International Safe Transit Association. Web. 19 Oct. 2010. ISTA 3A Packaged Products for Parcel Delivery System Shipment (150 lb.) or Less <http://www.ista.org/pages/procedures/ista-procedures.php>.

• "Procedures." International Safe Transit Association. Web. 19 Oct. 2010. ISTA 3A Packaged Products for Parcel Delivery System Shipment (150 lb.) or Less <http://www.ista.org/pages/procedures/ista-procedures.php>.

Acronym Definitions • ISO, International Standards Organization, European based. EN,

European National, is a designation for a standard considered as required in the European Union.

• CE, a mark without an exact word meaning, is generally considered a certificate of compliance to European Union regulations or standards for product sold in Europe.

• FDA, Food and Drug Administration, a USA regulatory group charged with public safety of medical devices for this paper.

• USA, United States of America.• AAMI, Association for the Advancement of Medical Instrumentation, is a

group dedicated to developing good medical device guidelines, practices, and standards for medical device/equipment use. Sterilization standards are developed within the group which developed into packaging as a method to maintain product sterility.

• TIR22, Technical Information Report, a guideline document for compliance to the ISO 11607-1 & -2 standards from AAMI.