Package Integrity Testing...DIFFUSION – particle is intercepted by fiber due to Brownian motion, may also be due to electrostatic attraction. Porous materials constructed with a

Package Integrity

TestingAn SPMC White Paper INSIDE

Package Integrity - Simply Put .......................2

Package Integrity versus Seal Strength ..........2

Challenge: Must Do Integrity Testing ..............2

Microbial Barrier ............................................3

Event Driven ...................................................3

Examples of Integrity Concerns ......................4

Types of Integrity Tests ...................................4

Integrity Test Method Applicability ................5

Seal Integrity .................................................5

Whole Package Integrity ............................ 6-7

Tray Integrity ..................................................8

Test Method Selection ....................................8

Detection Level ........................................ 9-10

Summary of Test Method Selection ..............10

SPMC Technical Group and ASTM .................11

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| 2 | Package Integrity Testing Sterilization Packaging Manufacturers Council

Package Integrity Testing | An SPMC White Paper

PACKAGE INTEGRITY — SIMPLY PUTThe role of package integrity in the protection of a medical device has a crystal-clear objective – protect the product by maintaining sterility. How one measures package integrity and decides what testing approach to use can be a challenging task.

In this paper the SPMC provides information on a set of ASTM International consensus standards for integrity that can help in the decision-making process. Using tables, charts and graphs that organize and describe relevant aspects of the standards this paper serves as an aid to those packaging engineers selecting the method and creating the rationale for use. Since there is no single method for measuring package integrity that will fit all products in all situations, there are no specific recommendations given as the applications and the rationale for use can only be defined by the medical device manufacturer.

Package integrity — the

physical capability of a

given package to protect its

contents with the desired

level of protection over a

defined period of service;

for example, as a barrier to

physical, microbiological or

chemical challenges

ASTM F17-17

Standard Terminology Relating to Primary Barrier Packaging

Package Integrity versus Seal StrengthIntegrity tests help verify, discover, or determine the presence of a compromised seal or a breach of whole package integrity; they do not, however, determine the force required to open a package. A package measuring acceptable seal strength may not pass integrity testing if there is a seal channel or hole in the material. It is, therefore, important to distinguish between these critical measures and understand which test methods are designed to be used for each. In this paper, the focus is on the consensus standards that have been developed specifically for integrity testing.

Challenge: Must Do Integrity TestingMedical device packages must be tested for integrity. At this time, there is no industry-accepted maximum hole size below which package integrity can be guaranteed; however, packages that protect medical devices must still be tested to some level for integrity. The decision of how to do this and what methods to use are a challenge for both producers and users. There are many standardized methods for which packages can be evaluated. The challenge is to select the appropriate method for each specific application.



Microbial BarrierThere are two ways to prevent microbes from harming the patient; the first is to kill any microbes in and on a medical device and its associated packaging, and the second is to prevent other microbes that will be encountered during distribution from reaching the patient. Microbial termination is achieved through effective sterilization. The function of the package is to maintain that internal environment encapsulating the device through distribution, where it will be exposed to potentially harmful microbes.

Microbes have no motility of their own and must be conveyed on particulate or in liquids through the package to put a patient at risk . A driving force, such as a pressure differential between the environment and the package, or capillary action, sets up the potential for microbial ingress. Nonporous materials block the passage of air that can carry microbes into the package. Porous material designed as effective microbial barriers create a torturous path that allows air to enter the package but filters out the microbes. Since the package serves as the primary barrier against microbial penetration, there is a need for a measurement of its integrity.

Event Driven

Each sterile barrier system integrity test selection may be driven by different aspects of product, process, distribution cycles and end use at aseptic presentation. The events that can occur during a package lifecycle can challenge the maintenance of sterility that would normally remain intact.

Three Mechanisms of Filtration INTERCEPTION – particle is captured when airstream passes sufficiently close to a filter fiber.

INERTIAL IMPACTION – particles travelling at high flow rates contact and are stopped by filter fiber.

DIFFUSION – particle is intercepted by fiber due to Brownian motion, may also be due to electrostatic attraction.

Porous materials constructed with a torturous path act as a filter to enable sterilization and restrict particles from entering the sterile barrier.

Typical Packaging Lifecycle



Examples of integrity concerns that can occur include material punctures, tears, seal openings, holes, etc.

Types of Integrity Tests

Visual Bubble Emission (submersion) Pressure/Vacuum Decay

Dye Penetration Trace Gases

Puncture Gouge Through Film Tyvek Damage Tray Flange Damage Abrasion Hole at Fold



Integrity Test Method ApplicabilityThe following tables provide a list of integrity tests organized under the functional use of the test area with title and brief description. More information in summary form for description and notes on applicability can be found in ASTM F2097 Standard Guide for Design and Evaluation of Primary Flexible Packaging for Medical Products

— SEAL INTEGRITY —

ASTM Test Method Description and Key Points About the Method

F1929 Dye

Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration• Dye solution is applied to seal edges. Dye is drawn into channels by capillary action• Method requires a clear side for visual inspection sealed to a porous material.• Potential for false positives in porous materials increases when foldedii

F1886 Visual

Test Method for Determining Integrity of Seals for Medical Packaging by Visual Inspection• Identifies inspection lighting minimums, provides a list of visual defects with potential causes in the appendix. Is used on

packages with at least one clear side to view seal channels

F3039 Dye

Standard Test Method for Detecting Leaks in Nonporous Packaging or Flexible Barrier Materials by Dye Penetration• Provides two methods for leak testing non-porous package- channels in seals and pinholes in material• Recipe for dye solution is different than that of F1929 porous package testing

F3004 Ultrasound

Test Method for Evaluation of Seal Quality and Integrity using Airborne Ultrasound• Detects seal defects to 1mm and characterizes seal quality using airborne ultrasound technology



— WHOLE PACKAGE INTEGRITY —


D3078 Bubble Test Method for Determination of Leaks in Flexible Packaging by Bubble Emission• Test is run in a vacuum chamber to create a pressure differential between headspace gas in package and the chamber.

Package is submerged in water. Exposes gross leaks through bubble emission.

F2228 Trace Gas

Test Method for Non-Destructive Detection of Leaks in Medical Packaging Which Incorporates Porous Barrier Material by CO2 Tracer Gas Method with CO2 during the test• This test method utilizes CO2 sensing techniques to evaluate packages for pinhole, cracks and channel leaks. • Used on rigid trays with porous lids it tests the tray and seal areas only. Defects in the porous lid are not detected. The

porous material serves as a vent for filling tray with CO2 during the test.

F2095 Pressure Decay

Test Methods for Pressure Decay Leak Test for Flexible Packages With and Without Restraining Plates• Measures leaks in nonporous film, foil, or laminate flexibles and foil-sealed trays• Package is pressurized. Transducer measures change (decay) in pressure over time.• Restraining plates, when used, limit the volume to increase sensitivity of the test

F2096 Bubble Test Method for Detecting Gross Leaks in Medical Packaging by Internal Pressurization (Bubble Test)• The package is inflated underwater to a predetermined pressure then is observed for a steady stream of air bubbles. Annex

defines a method for establishing a test pressure for each package size and material• Interpretation of bubble stream is subjective, dependent on training and experience. Potential for false positives in porous

materials increases when folded

F2338 Vacuum Decay

Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method• This test method detects package leaks by measuring the rise in pressure (vacuum loss) in an enclosed evacuated test

chamber containing the test package.• Test is non-destructive. Requires a test chamber designed for each package design

F2391 Trace Gas

Test Method for Measuring Package and Seal Integrity Using Helium as the Tracer Gas• Describes 2 test procedures: Sniffer Mode (sensor is moved around package to scan for He) and Vacuum Mode (utilizes a

vacuum chamber to measure He leak rate)• Helium is introduced into the package either before or after sealing.



— WHOLE PACKAGE INTEGRITY (continued)—


F2714 Fluorescent Decay

Test Method for Oxygen Headspace Analysis of Packages Using Fluorescent Decay• Uses fluorescent decay to measure change in oxygen concentration; the volume of the container’s headspace must be

known • A fluorescent dye polymer on a glass or flexible clear plastic dot is adhered to the inside of the package Temperature

has an effect on the observed decay rate.

F3039 Dye Penetration Standard Test Method for Detecting Leaks in Nonporous Packaging or Flexible Barrier Materials by Dye

Penetration• Uses dye injected into the package in a volume relative to the longest edge of the pouch or tray. Seals of packages are

examined for dye penetration into the seal - visually for transparent packages and by blotting of the external edges onto absorbent material for opaque packages

• Detects for channel leaks equal to or greater than 50µm (0.002in) in edge seals through a nonporous package

F3169 Vacuum Deflection Standard Test Method for Leak Detection in Blister Packaging by Vacuum Deflection Method by Laser

Measurement• Detects leaks in blister packs by measuring the deflection of surface in response to an applied vacuum. Requires

tooling and test chamber to hold blister pill packs

F3287 Mass Extraction Standard Test Method for Nondestructive Detection of Leaks in Packages by Mass Extraction Method

• Measures leaks by mass flow extracted while package is enclosed inside an evacuated test chamber• Mass extracted from the test package into the vacuum test chamber flows to the vacuum reservoir through the

Intelligent Molecular Flow System (MFS) to equalize the system. Mass flow rate from the vacuum chamber to the vacuum reservoir is measured by the IMFS. Based on the conservation of mass law, mass flow into the closed system is equal to the mass loss from the test package.



— TEST METHOD SELECTION —

ASTM Test Method by Material & Package Type Porous Non-

PorousRigid Tray Flexible Clear

MaterialOpaque Material

F1929 (Dye) X X X X (one side) X (one side)

F2096 (Bubble) X X X X X X

F1886 (Visual) X X X X X X (one side)

F2338 (Vacuum Decay) X X X X X X

F2228 (Trace Gas) X X X X

D3078 (Bubble) X X X X

F2227 (Trace Gas) X X (no lid) X X

F2095 (Pressure Decay) X X X X X

F2391 (Trace Gas) X X X X X

F3039 (Dye) X X X X

F2714 (Fluorescent Decay) X X X X X (one side)

F3004 (Air Ultrasound) X X X X X X

F3169 (Vacuum Decay) X blister X X

F3287 (Mass Extraction) X X X X

D5094 (Leakage) Xcontainer

w/threaded closure

X X

— TRAY INTEGRITY —ASTM Test Method Description and Key Points About the Method

F2227 Trace Gas

Test Method for Non-Destructive Detection of Leaks in Non-sealed and Empty Medical Packaging Trays by CO2 Tracer Gas Method• Method was developed to test trays without lidding



Detection LevelThe ASTM test methods are published with results of interlaboratory study (ILS) testing performed by volunteers supporting the subcommittee and task group writing the draft documents. This data is analyzed for repeatability and reproducibility so that users can have a measure of the precision of the test method. Preparing the defect samples for testing integrity is a challenging job. Some sensitivity data is limited by the ability to create small defects. For example, F1929, a dye penetration test for seal channels

in porous packages, measured channels in seals made by 50 micrometer wires. The test may be able to measure smaller channels; however, making the defects is not easily repeatable.

For each of the above tests, it is important to read and understand how the ILS was conducted and how the precision and bias conclusions were arrived at. At times, it may be helpful to request a copy of the research report, referenced in each test method in the ILS section.

ASTM Test Method Sensitivity

F1929 Dye 50 μm (0.002 in)

F1886 Visual 75 μm (0.003 in)

F2227 Trace Gas 50 μm (0.002 in) diameter

F2228 Trace Gas 100μm (0.004 in) in seal and 50 μm (0.002 in) diameter pinholes.

F2095 Pressure Decay 1 x 10−4 sccs (12.7μm) (standard cubic centimeters per second)

F2096 Bubble 250 μm (0.010 in)

F2338 Vacuum Decay 50 μm (0.002 in) in diameter, seal area of 125 μm (0.005 in), cracks or holes 100 μm (0.004 in)

F2391 Trace Gas 1 x 10-10 sccs (0.5 μm est.)

F2714 Fluorescent Decay % decay levels 0.04, 1.02 and 5.05% were tested

F3004 Air Ultrasound Channels of 1,000 μm to 3,000 μm

F3039 Dye 50 μm channel in seals, 10 μm pinhole

D3078 Bubble 1 x 10–5 sccs (0.5μm est)

F3169 Vacuum Decay Blister pill packs 15 µm, 50 µm holes

F3287 Mass Extraction 75 μm (0.003 in)



Summary of Test Method SelectionThe tables, information sorts and details on this list of ASTM integrity tests are compiled as tools to reveal some of the benefits and limitations of each approach to package testing. Creating a matrix of properties helps to narrow down the selection process. Use the following list of factors to begin:

• Porous vs. non-porous materials

• Clear vs. opaque materials

• Package type, tray vs. pouch

• Destruct vs. non-destruct

• Sensitivity of the method

• Cost of equipment and materials

• Volume of packages to be tested (time and quantity)

• Number of package configurations

• Packaging material

• R&D vs. production usage



Notes i Bahnfleth, W.P, Whittam, T.S., etal, Filtration of Airborne Microorganisms: Modeling and Prediction, ASHRAE Transactions: Research, p 4273ii Porous Sterile Barrier Integrity Testing: Failure Anomalies, Curtis Larsen, Medical Device & Diagnostic Industry, January 2006 • Copyright © 2006 Canon Communications LLC

SPMC Technical Group and ASTMThe SPMC Technical Group involvement in ASTM subcommittees has been a proven and longstanding commitment to medical device and packaging industries. Along with other packaging experts from medical device, food and consumer goods, testing laboratories, test device OEMs, logistics companies and others, we have worked to continuously create and improve consensus standards and to educate others in the value of their use.

We encourage others to contact us to suggest ways to improve these methods, to ask questions and to identify gaps in the current packaging standards. Contact us through the FPA site at www.sterilizationpackaging.org and post a question in our FAQ area or contact one of our member company contacts directly.

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Documents

Package Integrity Testing...DIFFUSION – particle is intercepted by fiber due to Brownian motion, may also be due to electrostatic attraction. Porous materials constructed with a