implement best practices for packaging and … tray sealer pouch bar sealer image courtesy alison...

Implement Best Practices

for Packaging and Shipping

Validation

Copyright GCI, LLC 2015

1. Qualify the packaging materials,

2. Test the package, and

3. Validate the packaging/sealing processes


International Standard, ISO 11607, Packaging for

terminally sterilized medical devices, simply states

you must:

Key Considerations for Packaging

Seal integrity

Expiry date

Microbial barrier

Product protection

Stability testing


What’s the Purpose of a Sterile Package?

Protect the product

Maintain sterility until the product is used

Allow easy opening and dispensing

Provide for product identification, cautions and use through labeling and graphics

UDI:

9/24/13 Rule published

9/24/14 Class 3 P/L, stand-alone SW

9/24/15 Life supporting/sustaining devices P/L/device, SW

9/24/16 Class 2 P/L and Class 3 devices

9/24/18 Class 1 P/L and Class 2 devices

9/24/20 Class 1 devices


Sterile Packaging Design Qualification

1. Design Qualification

A. Materials qualification

B. Package design

C. Package testing

i. Package performance

ii. Package integrity

iii. Seal strength

2. Process Validation


1.A. Materials Qualification

Shelf life

Storage and Transport

Sterilization method

www.sterigenics.com


1.A. Materials Qualification - Considerations

Microbial barrier

Toxicity/biocompatibility

Physical and chemical properties appropriate for the package needs

Compatibility with the sterilization process

Compatibility with the forming and sealing processes to be used

Any shelf life limitations


1.A. Materials Qualification

Real time aging @ ambient conditions

Accelerated aging @ elevated conditions


1.B. Package Design Criteria

Product requirements

Shape

Weight

Protection

Method of sterilization

EO

Gamma or e-beam

Manufacturing method

Packaging

Sealing

Labeling and graphics


Package Design

Automatic form, fill and seal for high volume, rigid or flexible blisters

Image courtesy Alison Gitlin, University of Miami, April 2014.

Package Design Manual or semi-automatic sealing for pre-formed blisters or pouches

Blister tray sealer Pouch bar sealer

Image courtesy Alison Gitlin, University of Miami, April 2014.

Labeling and Graphics

Preprinted or printed in-line

Variable information

Multi-lingual labeling

Instructions for opening the package

Legal requirements


1.C. Package Testing

Package Performance

Following simulated distribution

Package Integrity

Sterility

Seal Strength

Burst

Tensile


1.C. Package Testing

Simulated

Over-the-road

Damaged Product

Sterility Maintained


1.C.i. Performance testing

ISO 11607-1:2006, 6.3.4 Performance testing shall be conducted on the

worst-case sterile barrier system produced at the specified process

limits of forming and sealing and after exposure to all the specified

sterilization processes.

Specified sterilization processes may include multiple exposures of

the same or different sterilization cycles.

ASTM D4169 or ISTA 2 Series


Test Path (2 yr. shelf life)


BP #17

Tie Risk to Sampling (nominal v. L/C)


BP #8

Sample Conditioning

All packaged devices, with appropriate labeling and DFU, will be exposed to

two (2) EO sterilization cycles per the validated cycle (BP #9). They will then

undergo Climatic Conditioning and Distribution Simulation, followed by

accelerated aging, prior to the start of DV testing. All T=0 (baseline) samples

will undergo 2X EO sterilization, Climatic Conditioning and Distribution

Simulation.


Accelerated Aging Time at 55˚C with Ambient Temperature of 25˚C

Shelf Life (months) 13 25

Shelf Life (days) 396 761

Accelerated Aging Time (days) 50 95

BP #10: Add 1 mo. for Japan

Performance Testing of Shipping Containers (ASTM D4169-DC 13)

1 2 3 4 5 Sequence

Distribution

cycle

Air (intercity) and motor freight (local) single package up to 150 lb.

Test type Climate hazard

Manual

handling

Manual

handling Vehicle

stacking Vehicle

vibration Loose-load

vibration

Test simulation hazard

temp moisture humidity

drop drop compression repetitive shock vibration

ASTM Test Method

D 4332 D 5276 D 5487

D 642 D 999 D 4728 D 5276 D 5487


Laboratory Shipping Test Equipment

Vibration Compression

Drop Copyright GCI, LLC 2015

Images courtesy Alison Gitlin, University of Miami,

April 2014.

Accelerated Aging Factor (AAF) = Q10 (Te - Ta)

/10

Where: Ta = Ambient Temperature = 20o- 25

o C

Te = Elevated Temperature 60o C

Q10 = Reaction Rate = 2.0

Desired Real Time/AAF = Accelerated Aging Time (AAT)

Example:

What is the accelerated aging time at 50oC for 5 yrs.?

AAF = 2.0 (50-25)/10

= 2 2.5

= 5.66

60 mos./ 5.66 = 10.6 mos.

Accelerated Aging Factor


BP #275: Rationales for not testing product at aged intervals must be documented in protocol.

BP #276: Build sufficient samples to test at intermediate intervals.

BP #277: Run a notebook study first to characterize performance.

1.C.ii. Package Integrity Test Methods

Visual inspection

Weight gain/loss

Submersion bubble test

(internal pressure)

Dye tests (vacuum &

capillary action)

Ultrasound

Lid deflection

(pressure differential)

Electrical conductivity

Capacitance

Tracer gases (CO2 , O2 , He)

Vacuum/pressure decay


BP #4: Perform TMV to assess R&R and sensitivity.

Dye Penetration

Visual Inspection

Vacuum Leak

Typical Package Integrity Tests



April 2014.

1.C.iii. Seal Strength (Burst Test)

A quantitative measure of the package’s ability to withstand pressurization.

Cautions: no direct correlation with seal

peel strength as measured by tensile.

not intended to evaluate package integrity

low sensitivity to sealing process changes.



April 2014.

1.C.iii. Seal Strength (Tensile Test)

Force to pull open a seal

Samples: cut to a width of 15mm or 1 inch

Record average force or total energy

(Newtons/meter, pounds-force/inch of width)

Excellent measure for SPC, capability and

package failure analysis


April 2014.

Test Method Validation

Define an acceptable seal

Select the most appropriate test

Produce consistent defects

Establish sensitivity

Run pilot study

Determine method repeatability

Demonstrate reproducibility


BP #6: Perform limited TMV on standard methods (e.g., implementation and operator training).

….

..

….

..

precision

accuracy

3. Packaging Process Validation

IQ sealer and packaging equipment in place.

OQ characterization testing with DOE.

PQ packaging and sealing processes to process specifications.

PPQ packaged product pre-sterile, no aging, no distribution

simulation. Can be used as t=0 Design Verification test units.

BP #3: On-going process verification / SPC includes tensile test of 1” seal section at

beginning and end of each lot.


Enforcement

From 1/1/2014 to 9/1/2015, there were 500 medical device

recalls for packaging issues

Incorrect packaging material Tears and pinholes in pouches

Potential for breach in sterility Channels in the seals

Counterfeit product mixed with authentic

product

Firm did not have packaging validation to

support the labeled shelf life

Packaging seals may not be intact Cracks/ holes in packaging tray

Does not meet specifications Missing components


Benchmarking: Not performing TMV (method defect detection capability) on in-process and final

release test methods

Not ensuring environmental storage integrity with logged activities and

certified/calibrated recording equipment

Temperature excursions not investigated and impact documented

Not considering MDD above ISO 14971:2007 which mandates reduction of risks AFAP

Not linking sampling plans in RI and V&V to risk documents and complaints

Not stacking challenge conditions or reducing statistics based on limit/challenge

conditions

Not updating FMEAs, HAs regularly with post market data & revalidating if needed

Rationales for not testing product at aged intervals not documented

Not using DOE to characterize process inputs and outputs


References

Goode, Roberta D., “Planes, Trains and Automobiles: Simulated Distribution of FDA-

Regulated Products for Packaging Validation,” Journal of Validation Technology, Vol. 9,

No. 2, February, 2003.

ISO 11607-1:2006 Packaging for terminally sterilized medical devices – Part 1:

Requirements for materials, sterile barrier systems and packaging systems.

ISO 11607-2:2006/Amd 1:2014 Packaging for terminally sterilized medical devices - Part

2: Validation requirements for forming, sealing and assembly processes.

ISO/TS 16775:2014 Packaging for terminally sterilized medical devices -- Guidance on

the application of ISO 11607-1 and ISO 11607-2.

ASTM D4169 - Standard Practice for Performance Testing of Shipping Containers and

Systems.

http://www.sterigenics.com/services/medical_sterilization/contract_sterilization/mate

rial_consideration__irradiation_processing.pdf

FDA Guidance “Container and Closure System Integrity Testing in Lieu of Sterility Testing

as a Component of the Stability Protocol for Sterile Products,” February, 2008.

Compliance Dates for UDI Requirements:

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentif

ication/CompliancedatesforUDIRequirements/default.htm

http://www.sterigenics.com/services/medical_sterilization/contract_sterilization/material_consideration__irradiation_processing.pdf

http://www.sterigenics.com/services/medical_sterilization/contract_sterilization/material_consideration__irradiation_processing.pdf

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/CompliancedatesforUDIRequirements/default.htm



Roberta Goode

[email protected]

www.GoodeCompliance.com

(954) 399-7510


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