Patient Safety: Medical
Device Distribution
Evaluation and Sterile Barrier
System Integrity
Jan Gates, VP Client Solutions, Adept Packaging
Jane Severin, VP Technical Solutions, Network Partners
ASTM Work Shop , 11 October 2017
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OBJECTIVE
Present information on package distribution simulation and
sterile barrier integrity testing
Describe ASTM tests to assist in meeting regulatory and
standards requirements
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DISCLAIMER
These slides
are our
opinions,
based on our
60+ years’
experience,
and not
necessarily the
opinion of the
companies we
represent.
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AGENDA
ISO 11607-1/-2 Overview
ISO 11607-1/-2 Design and Validation Specifics
• Design and validations
• General requirements
• Process validations
• Packaging validations
• Test methods validations
• Microbial/whole package integrity
• Microbial testing
• Integrity Testing
Shipping and Important Considerations
The Last 1000 Feet
Proposals
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Packaging For Terminally Sterilized
Medical Devices —
Part 1: Requirements for Materials, Sterile Barrier
Systems and Packaging Systems
Part 2: Validation Requirements for Forming,
Sealing and Assembly Processes
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ISO 11607-1/-2 STANDARDS
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ISO 11607-1/-2 STANDARDS
Outlines the packaging design, development and testing
Over 150 “shall” statements in the two documents
FDA harmonized with the standard in November 2006
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ISO 11607-1/-2 VALIDATION SPECIFICS
Validating a sterile barrier system involves four different types of
validation activities:
• Design
• Packaging Process
• Sterilization
• Test Methods
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ISO 11607-1 DESIGN
Design
• 6.1.1 The Packaging System shall be designed to minimize the
safety hazard to the user and patient under the intended specified
conditions of use.
Accomplished with the use of risk assessment and mitigation
techniques-output examples: Component and Process
Specifications, process knowledge, user needs, etc.
Develop pre-determined requirements for the design
Validation provides objective evidence that the requirements have
been met; ‘design outputs = design inputs’
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ISO 11607-1 DESIGN VALIDATION
Design Validation <definition>
3.28 validation
• (general) confirmation by examination and provision of objective evidence that the particular requirement for a specific intended use can be consistently fulfilled.
Consists of two elements - Industry practice to conduct these tests as independent studies
• Package Performance Testing - A physical evaluation to demonstrate that the packaging system is adequate to protect the product throughout distribution, handling and storage
• Stability Testing - A chemical and physical evaluation to demonstrate that the SBS maintains integrity over time. Basis for expiry claims.
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TRANSPORTATION
Will your design survive?
Copyright © 2013 DuPont.
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DESIGN AND VALIDATION ARE KEY…
Examples of sterile packaging failures:
Seal Creep Seal Failure Transport Damage
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ISO 11607-2 PROCESS VALIDATION
Process Validation <definition>
• 3.16 validation (process) documented procedure for obtaining,
recording and interpreting the results required to establish that a
process will consistently yield product complying with predetermined
specifications.
Provide documented, objective evidence that the packaging
process is in statistical control, is repeatable, and makes product
that meets predetermined specifications.
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• IQ Installation Qualification - Verify equipment is correctly
installed and functional, including all high and low settings
• OQ Operational Qualification - Defined process window
(seal)
• PQ Performance Qualification - Adequate process control
and capability
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PACKAGING SYSTEM QUALIFICATIONS
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EN ISO 11607:2006 - SECTIONS 1 TO 4
General Requirements
Test Methods
• All test methods, including non-standardised ones, shall be validated and documented
• Note: ISO 11607-1, Annex B contains a list of suitable test methods
Test method validation shall include
• Rational for selection of appropriate tests
• Establishment of acceptance criteria
• Determination of repeatability (r)
• Determination of reproducibility (R)
• Establishment of sensitivity for integrity tests
Needs interlaboratory check and comparison with published test method r & R
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PACKAGE VALIDATION - ISO 11607-1:2006
➢ 5.2.3: Porous materials shall provide an adequate microbial barrier to microorganisms in order to provide integrity of the sterile barrier system and product safety.
➢ 6.3 Packaging-system performance testing
➢ 6.3.1 Integrity of the sterile barrier system shall be demonstrated after
sterilization and subsequent performance testing.
➢ 6.3.2 Physical tests, along with microbial barrier testing of porous
packaging materials, can be used to establish the capability of the
sterile barrier system to maintain sterility.
➢ 6.3.3 In the absence of applicable validated tests (for the complete
package), microbial barrier performance requirements can be
established by testing:
➢ The microbial barrier properties of materials
➢ The integrity of seals and closures
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TWO FUNDAMENTAL QUESTIONS
Why is Microbial Barrier Important?
• The key factor in selecting packaging materials for medical
devices is the ability of the package to maintain sterility
from the point of sterilization until it is opened for use
➢ Why is Microbial Barrier Testing Important?
• Need to understand how the packaging material will perform
as a microbial barrier during handling, distribution and
storage; post sterilization
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MICROBIAL BARRIER TESTING
Traditional Whole Package Microbial Challenge
• HIMA Study comparing whole package test and physical tests
o Dye and Visual
o Found a significant difference; Whole Package Challenge found to be unreliable
and fraught with false-positives
o Hansen, J; Jones, L. et al (1995) In Quest of Sterile Packaging; Part 1 Approach
to Package Testing MDDI 17(8) 56-61
• Current practice is to use material microbial testing for porous substrates and physical testing for finished packages
o ASTM F1608-16 Standard Test Method for Microbial Ranking of Porous Packaging
Materials (Exposure Chamber Method)
o ASTM F2638-12 Standard Test Method for Using Aerosol Filtration for Measuring the
Performance of Porous Packaging Materials as a Surrogate Microbial Barrier
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PACKAGE INTEGRITY TEST METHODS
ASTM F1886 Standard Test Method for Determining Integrity of
Seals for Medical Packaging by Visual Inspection
• 75 micron (60-100% Probability)
ASTM F2096 Standard Test Method for Detecting Gross Leaks in
Medical Packaging by Internal Pressurization (Bubble Leak Test)
• Sensitivity Down to 250 micron
ASTM F1929 Standard Test Method for Detecting Seal Leaks in
Porous Medical Packaging by Dye Penetration
• Sensitivity Down to 50 micron
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SENSITIVITIES
ASTM
Test
Type of Test Test Focus Destructive
?
Hole/ Channel
Size
F1886 Visual Inspection Seals No 75 μm
F1929 Dye Penetration Seals Yes 50 μm
F2096 Internal
Pressurization
bubble test
Package Yes 250 μm
F2228 CO2 tracer gas Package
(porous area
masked)
No 50-l00 μm
F2338 Vacuum Decay Package
(porous area
masked)
No 100-125 μm
F3004 Airborne
Ultrasound
Seals No Depending on
defect type
(750 μm)
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SHIPPING AND IMPORTANT
CONSIDERATIONS
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CALCULATING DIM
L= length
W = width
H = height
DIM = (L x W x H)/DIM ratio by carrier
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PALLET/BOX STRENGTH CALCULATIONS
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SIMULATED DISTRIBUTION TESTING
ISTA 3A, 3B, and 3E are FDA Consensus Standards (2016)
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/results.cfm
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SIMULATED DISTRIBUTION TESTING ASTM D4169 and D7386 FDA Recognized for many years
Common Usage
Assurance Levels – I and II used
Standard Distribution Cycle
Use
ASTM D4169 DC 4 Single package with pallet or skid, LTL motor
freight
ASTM D4169 DC 13 Air (intercity) and motor freight (local, single
package up to 150 lb. (61.8 kg).
ASTM D4169 DC 2 Specially defined distribution system, user
specified
ASTM D7386 Not
applicable*
Single parcel carrier shipments
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HEALTHPACK LIVE POLLING 2017
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ORIGINAL DISTRIBUTION CONSIDERATIONS
UseHospital
Manufacturer
Manufacturer
Manufacturer
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ASTM D4169 – may have trucks, planes or trains in the transit
ASTM D7386 – single parcel shipment added
Plane Transit
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MORE CURRENT DISTRIBUTION LANE
UseHospital
Manufacturer
Manufacturer
ManufacturerHome
Product
Trunk StockWhere does trunk stock occur?
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ASTM D4169 or D7386? More discussion later.
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CASE FILL
Full case of one product?
Mixed product loads?
Full pallet loads?
Potential to bulk ship to one location
(distributor) then individually or small
quantity ship to another location
(customer)?
Last mile issues
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MIXED LOAD SHIPPING
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ONE SIMPLE U.S. DISTRIBUTION LANE
Ship to hubTransfer/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
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DISTRIBUTION MAPPING –DETAILED MULTIPLE SHIPPING COUNT EXAMPLE
Domestic System and Domestic Repetition
Round trip Handling Truck Transit Plane Transit Compression
1 23 6 1 3
2 47 13 3 7
3 71 20 5 11
4 95 27 7 15
5 119 34 9 19
6 143 41 11 23
International System and International Repetition
Round trip Handling Truck Transit Plane Transit Compression
1 37 10 3 7
2 77 21 7 15
3 124 32 11 23
4 171 43 15 31
5 218 54 19 39
6 265 65 23 47
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2
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LAST 1000 FEET/LAST MILE
► Unexpected situations occurring
before use
UseHospital
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HEALTHCARE ASSOCIATED INFECTIONS
► CDC reports that the causal agent is not known for roughly 30% of HAIs in the US
► Could packaging materials be a contributor?
► What are the elements that medical devicepackaging are exposed to that could impact thebarrier?
► Do you know what your product is exposed to inhealthcare facilities once removed from shipping container?
► How do current test methods for microbial barrier provide meaningful data?
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PROPOSALS1. Last 1000 feet investigation work group developed?
• Important for us to collaborate closely with healthcare
• Should an new work group be developed in ASTM for
this work?
• Task force formed to evaluate whole package
microbial testing?
2. Mixed load work group, D10.21.05
• Currently being developed as an ‘e-commence’ work
group and subsections are possible
• Add drone shipping to the schedules?
3. Volunteers?
• Let us know…..
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QUESTIONS?
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CONTACTS
Jan GatesVice President, Client Solutions
Phone/Cell: 650.743.5780
E-mail: [email protected]
Website: www.adeptpackaging.com
Jane Severin, PhD, CPPVice President, Technical SolutionsPhone/Cell: 248.408.0127
E-mail:
Website: www.networkpartners.com