packaging configuration. Control FDA Inspection Categories (cont.) 3) Production and Process...

Sterile Barrier Packaging:Common Causes of Failuresand How to Prevent Them

Wendy Mach, RM (NRCM), CQA (ASQ)

Packaging Section LeaderNelson Laboratories

Sterile Barrier Packaging:Common causes of failures

and how to correct them

Wendy Mach, B.S., RM (NRCM), CQA ASQ, CPLP (ISTA) Packaging Section Leader

801-290-7810 wmach@nelsonlabs.com

www.nelsonlabs.com

Copyright Nelson Laboratories 2014 1

Agenda

• Purpose of Packaging

• Standards

• Test Methods/Failures

• Sample prep

Purpose of Packaging Testing

• Evaluate the performance of each sterile barrier system or packaging system before selection and implementation to ensure conditions for sterilization, storage, and handling.

• Can be a requirement – FDA

• Can be guidance – European ISO

Control

FDA Inspection Categories (observed during review of sterilization validation) 1) Supplier Problems New supplier/material not qualified Packaging process not validated Pin holes 2) Design Device in the seal Sharp edges Package too small Wrong packaging configuration

Control

FDA Inspection Categories (cont.)

3) Production and Process Controls

Improper line clearance

Incorrect parameters used for sealing

Equipment changes not validated

4) Personnel Problems

Not following procedures

Inadequate training

Not following procedures

Current Standards

ANSI/AAMI/ISO 11607 part 1 & 2

Part 1: Materials and Sterile Barrier

Requirements

Part 2: Forming, Sealing and Assembly

Approved as the FDA consensus

standard

6 Copyright Nelson Laboratories 2014

ISO 11607

The document divides the testing into 2 separate area’s:

• Performance Characteristics –

– temperature, humidity, pressure, light, cleanliness, electrostatic conductivity

• Package Properties

– microbial, physical and chemical properties, sterilization compatibility

ISO 11607

• Evaluated through all intended processes

– Sterilization

– Handling

– Distribution

– Storage

• Include all materials – IFU, labeling

ISO 11607

• Evaluated for expected worse case scenarios

– Medical Device (heavy, light, sharp)

– Material (porous , nonporous)

– Manufacture parameters (sealing)

– Sterilization (single, multiple)

– Distribution, storage, handling

Typical Validation Plan

Shipping studies early-

feasibility

Ship prior to all

performance & stability

Perform 3 tests:

strength, integrity, microbial

3 lots/batch

of 11 samples

Perform baseline testing -

Performance

Use same tests

throughout

Minimum of 3 points for entire process

Strength Integrity Microbial Barrier

Seal Peel Dye Migration F1608

Burst Test Dye Immersion Microbial challenge

Creep Test Bubble Emission F2638-07

Visual Inspection

Common Packaging Tests

Packaging tool

Available at Nelson Labs Booth #812

Visual Inspection ASTM F1886

Visual Inspection is a process of methodically and purposefully examining a package for a specific range of defects and recording observations.

Visual Inspection Channels

Bubble test failure, due to channels in the seal. The area circled in red, shows the emission of bubbles from a single point in the seal.

Dye Migration failure, due to channels in the seal. The channels are indicated by the areas where the blue dye traveled through the entire width of the seal.

Visual Inspection

Example of crease through a seal.

Visual Inspection

Visual Inspection Undersealed

Open seal

Nonhomogeneous seal, lacks uniformity in color.

Unsealed Areas

This is an example of an opened seal on a Tyvek pouch

Visual Inspection Oversealed

Clarified Seal

Slightly

clarified seal

Oversealed foil pouch

Leakage through a seal, due to oversealing of Tyvek

Narrow Seal, due to tray misalignment

Narrowing of seal, due to internal creep, which was caused by warping of the tray

Narrow Seal, due to internal creep

Visual Inspection Narrow Seals

Seal Peel Test

Seal Peel Test ASTM F88

Determines the strength of the seal at a specific place on the package

2 seals

•Manufacturer’s

•MDM Seal

Can be helpful in setting the

sealing parameters during IQ

testing

Measure a one inch segment

of the package along one of

the seals.

•cut the package so that there are 3

inches of material on each side of

the seal

Results are reported as load at yield

and energy to break

Seal Peel Test

Identifying the material in each grip is critical as it

can have an affect on the results.

Tyvek in mobile grip

Film in stationary grip

1 inch across

Seal Peel Test

90° Unsupported Usually provides the most conservative value (lowest)

Tail is free floating during the pull

Seal Peel Test

90° Supported

Tail is manually held with slight pressure during the pull

Seal Peel Test

Tail is held with a backing plate during the pull

180° Supported Provides values significantly higher than with tail in 90 ° position. Plate is placed in the stationary grip.

Seal Peel Test

Over sealed as a result of too high temperatures causing melting/bending of materials and voids in the seals.

Seal Peel Test

Delamination as a result of too high temperatures causing fiber tear.

Burst Test ASTM F1140

Determines package seal strength

Perform by pressurizing the package until it

bursts

Test system pressure is pre-set to a point above the known burst point

Results include the burst pressure data and a description where the seal failure occurred.

•This provides a better idea of where the stress points are located

Burst Test

Burst Failures

Dye Migration Test ASTM 1929

Determines the integrity of the package seal

Involves injecting dye into the package

•Placing the weight of the solution against each portion of the seal for a specific length of time

Examine package for evidence of seal failure

•Demonstrated by dye slipping through the seal

Dye Migration Test

Dye Migration Failure

~125um

Bubble Emission Test ASTM F2096

Determines the integrity of the package and the seal

Involves inflating the package and

submerging it into a surfactant solution

Package examined for evidence of seal failure or holes in packaging,

demonstrated by bubbles emerging through the seal

Bubble Emission Test ASTM F2096

Bubble Emission Failures

Tyvek® folds

Bubble Emission Failures

Microbial Ranking Test ASTM F1608

Determines the Log Reduction Value (LRV) of porous material

Sample size must be a

minimum of 47mm in width

Packages placed into a chamber

and exposed to a specific

organism (Bacillus)

Filters are blended and

plated to determine titer

values

Microbial Ranking Test

Microbial Aerosol Challenge

Determines the integrity of the whole package

Packages placed in an aerosol chamber and exposed to a specific organism (Bacillus)

Contents of the packages are then tested for the

presence/absence of the indicator organism

Indicator testing

Immersion

Media fill

ASTM F2638

• Measures aerosol filtration performance of porous materials

• Results in the max penetration of material

• Uses 1.0 µm latex spheres

ASTM F2638

Sample Prep

Sample Preparation

• Packages should be manufactured in a validated process

• Must be sterilized using validated sterilization processes including multiple exposures

• Should include device/facsimile labeling and IFU’s

Other tools…

• Microscopic examination

• Risk analysis

– Fishbone diagram

– Failure Mode Effectiveness Analysis (FMEA)

– Flow diagrams

– In-process reviews

• Test method validation

– Precision and bias

• Look at Product, Process, Package, People and Environment

Other tools…

Thank you

Wendy Mach, B.S., RM (NRCM) Packaging Section Leader 801-290-7810 wmach@nelsonlabs.com www.nelsonlabs.com

Don’t forget – the slide rule is available at Nelson Labs Booth #812

View additionalOMTEC 2014

speaker presentations.

www.OMTECexpo.com

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