Sterilization Compromising Sterile Barrier

Medical Device Packaging Tips, Learnings and Cautionary Tales

OMTEC 2015 Chicago Alison Tyler Technical Director Beacon Converters, Inc. June 2015

• Why is Medical Packaging so Important? • Packaging Guidance and Compliance Standards • Major decision points for selecting materials and packaging design • Review of Recent FDA Recalls

• 490,000 Americans have died in 5 year period due to medical errors. These were all categorized as preventable deaths 1. 1. Kohn LT, Corrigan JM, Donaldson MS, eds. To Err Is Human: Building a Safer Health 2. System (Washington: National Academy Press 1999)

831 practicing physicians 1207 members of the public

35% 291 Reported Medical Errors in their own care of family member care

Public

42% 507 Reported Medical Errors in their own care of family member care

Malpractice Cost of Insurance Companies Insurance Healthcare and Health Plans 29% 27% 22%

Cost of Cost of Prescription Healthcare Drugs 38% 31%

Medical Errors 5% So how big a deal are they really?

Medical Errors 6%

• 490,000 Americans have died in this 5 year period due to medical errors. These were all categorized as preventable deaths • 1. Kohn LT, Corrigan JM, Donaldson MS, eds. To Err Is Human: Building a Safer Health • System (Washington: National Academy Press 1999)

• Well, lets just say things aren’t pretty Current data estimates that annually as many as …. 440,000 Americans die every single year from preventable medical errors. This now ranks medical errors as the 3rd leading cause of death in the United States.

Hospital Safety Score

Source www.hospitalsafetyscore.org Highland Park Hospital Highland Park Hospital

Greater Boston Area

West Virginia

© 2012 Beacon Converters, Inc. So What Does this Have to Do with Packaging? • This is the same environment that packages will be opened in, one that is riddled with errors • You aren’t only going to sell your device in Boston.

• Your design must be easy to follow, must NOT contribute to any additional errors.

• You cannot depend on people working in this environment to police for package failures

• Lets get on to making great packages!

Guidance Standards – Use Them!

Packaging Guidance and Compliance Standards 1. AAMI/ISO- 11607 Packaging for terminally sterilized medical devices • Part 1- materials, sterile barrier systems and packaging systems • Part 2- Validation requirements for forming, sealing and assembly processes 2. AAMI TIR 22- Guidance for ANSI/AMMI/ISO-11607 Parts 1 & 2 (Don’t try to reinvent the wheel)

1. Protect the device from physical damage

2. Protect the device from undesirable environmental conditions

3. Allow device to be terminally sterilized

4. Allow that sterility to be maintained until the product is dispensed

5. Allow aseptic presentation

Design Inputs

• Product Attributes • Protection Requirements • Storage, Distribution and Handling Requirements • Manufacturing Requirements • Sterilization Requirements • Customer Requirements

© 2012 Beacon Converters, Inc. AAMI Standards TIR-22 (ISO 16775) Annex Information • Regulatory references • Test Method Validation • Sterilization Considerations • Design Inputs-Attributes & Requirements • Investigating Failure • Selection, Evaluation and Testing • Generating a Validation Protocol • Risk Analysis Tools

1• Protect your device from physical damage

• Puncture • Abrasion • Improper cushioning Glue flap • Crushing • Insufficient shielding Inside out / outside in puncture

© 2012 Beacon Converters, Inc. Design Inputs Protection from Physical Damage Predict Damage Possibilities with good inputs – Size, Profile – Weight – Center of Gravity – Fragile or rugged – Sharp edges or points – Surface Characteristics – Small component pieces – Bend Sensitive

• Multiple components of varying size and shape • Heavy, bulky handle • Fragile knob used to control the laser source • Large fluid reservoir • Bend-sensitive fiber optics and tubing

PMP News webinar archive: Reduce, Recycle, Recover: Redefine your sterile barrier system in a flexible footprint

Orthopedic Drill and Pin Kit

• Multiple components • Varied size/shape. • Sharp edged • Heavy (surgical steel). • Materials include steel and molded polymer parts.

Carbon Dioxide What conditions could harm or degrade your device and packaging system? Temperature Extremes Ultra Violet

Water Vapor Oxygen

Material (g-mil / 100 in2-day) (cc-mil / 100 in2-day) LDPE 1.2 510 LLDPE 0.8 280 HDPE 0.4 170 Ionomer 1.7 500 Cast PP 0.7 240 OPP 0.4 120 PET 1.2 2.3 BON 10 1.7 PVdC 0.1 0.1 PCTFE 0.015 9.8 AlOx PET 0.1--0.005 0.2--0.006 MVTR: 100°F, 90% RH OTR: 73°F, 50%RH

Typical Vapor Barrier Levels

MVTR (g/100 sq.in/day) 12 10 8 6 4 2 0

A60 AlOx PET

PCTFE

PVdC BON PET OTR OPP MVTR Cast PP Ionomer

Materials (0.001" caliper) Materials HDPE LLDPE LDPE

0 100 200 300 400 500 600 OTR (cc/100 sq.in./day)

Strength HDPE

PET Moisture Barrier

Oxygen Barrier PP UV Barrier Chemical Resistance LDPE

Seal Strength

Overwrap Bag for IV products • Active drug substance will degrade in light.

• Fluid loss affects drug dosage.

• Must be autoclaved to sterilize.

• Product visibility is required. Overwrap Bag for IV products Protection from Environment

FDA • UV Light Barrier protects active drug substance.

• AlOx Moisture/Oxygen Barrier prevents loss of fluid/drug effectiveness.

• Heat resistant layers are durable in high heat process temperatures of autoclaving.

• Bag is translucent for product visibility

• Bag designed for tear open application Tissue / Collagen Like Products Protection from Environment

A3460 A34 –Polyester/LDPE/Aluminum Foil/Seal layer A60- AlOx Polyester/Seal layer • Increase in products requiring very high barrier • Sometimes liquid is part of product • Low profile • Moisture loss critical 5 Major Points; Packaging Performance What does your package need to do?

3• Allow device to be terminally sterilized

• Porous or impermeable? • Compatibility with process – steam, autoclave, VHP, EO, Gamma and electron beam Guidance for ANSI/AAMI/ISO 11607 Sterilization Compatibility of Considerations materials subject to sterilization

• Steam Sterilization requires porous package – Paper with good wet strength – In some cases Tyvek can be used if temperature is less than about 121°C. • HDPe, PP, PA are common film webs incorporated into high temperature moist applications • Autoclave utilizes non-porous materials

© 2012 Beacon Converters, Inc. Sterilization Ethylene Oxide • Suitable for heat and humidity • Porosity must be sufficient to: – allow gases to penetrate or exhaust all layers – reach the interior of the product – minimize the stress on materials and seals (don’t mask Tyvek®)

• How many layers will surround product? • Primary and secondary packaging • Double or triple bagged • Kit building (all components must be considered) • Be Careful with labels

Sterilization Radiation- Gamma & E-beam

• Radiation – Materials must maintain their properties for desired shelf life protection – Package need not be breathable • Provide for outgassing – Radiation can be damaging to packaging materials, paper and polypropylene in particular. • Refer to TIR 17 or ask your supplier cumulative • Flexible packaging uses thin caliper materials, more affected by sterilization dosages • If re-sterilizing, re-package for safety and durability

© 2012 Beacon Converters, Inc. Sterilization VHP- Plasma • A hydrogen peroxide plasma is the primary sterilizing agent – Non-cellulose porous packaging needed – Process can be damaging to extrusion coated/laminated materials (adhesion to substrate is compromised) – Typical package: PET/PE adhesive laminate sealed to Tyvek

Allow that sterility be maintained until the 4 product is dispensed

• Compromise of Sterility is event related • Sterility is not time related • A sterilized object will remain sterile until an event compromises its sterility

© 2012 Beacon Converters, Inc. Sterilization Compromising Sterile Barrier • Package seal failures • Stressed in EO, improper seal strength specification • Package material failures • Abrasion, puncture, tear, material under/over engineered • Package damaged in manufacturing • Handling- manual or auto fills, damaged equipment • Package damaged in distribution • Pressure changes and non-porous packages, UV over exposure in storage

On June 3rd, 2014 Customed, Inc. initiated a recall of sterile convenience surgical packs. The products have been found to have a potential defect due to adhesion.

The defect could result in loss of product sterility and lead to infection . Reason for Recall: Surgical pack sterility may be compromised due to individual packs adhering to one another inside the shipping case. In some cases, the plastic packaging of one bag (along the printed words “SNAP SMARTLY TO OPEN”) has adhered to the end seal of an adjacent pack. When the bags are separated, the plastic film can tear and compromise the sterility of the contents.

© 2012 Beacon Converters, Inc. FDA Recalls Compromising Sterile Barrier Customed Inc., Surgical Convenience Packs Damaged Packaging How much product was included in the recall? ALL product manufactured from 1/9/2009- 5/20/2014

459,146 units manufactured 3,562 manufacturing lots

Products were distributed within the domestic (Puerto Rico Commonwealth, Florida State, New York State, US Virgin Islands); and international market (Geographical Area Central America- Costa Rica & Panama; and South America-Colombia).

Class 2 Recall Medela Enteral Syringe, Acacia Piston Syringe March 11, 2015

1,959,187 units recalled

The firm is recalling sterile enteral feeding syringes due to determining that the sterility of the affected products may be compromised as a result of a potential breach in packaging.

Class 2 Recall Ringloc Acetabular Shell Limited Hole Finned 52mm

Feb 17, 2015 Mallory Head 4 Finned Acetabular Shell 50mm (Lot 364600) and Ringloc + Acetabular Shell Limited Hole Finned 52 mm (Lot 427840) following a mix up in packaging with the two

FDA Determined Cause: PRODUCTION CONTROLS: Packaging Process Control

Class 2 Recall Pulsiocath PiCCO ProAQT Monitoring Kit

Feb 17, 2015 Internal testing and investigation of the packaging revealed cracks and holes in primary packaging

FDA Determined Cause: PRODUCTION CONTROLS: Packaging

Class 2 Recall Four Lead TUR Irrigation Set

January 26, 2015 Manufacturer Reason for Recall Potential for failure of the pouch packaging seal at high altitudes.

FDA Determined Cause: DESIGN: Packaging Design/Selection

Quantity in Commerce 26,028 units – Baxter Healthcare

Class 2 Recall cryoICE cryoablation probe (CRYO2)

December 30, 2014 19,190 units

Cryogenic probe for cardiac ablation surgery, packaged individually in Tyvek pouches. Affected product may have compromised sterility due to packaging defects. It was determined that some mishandling of the product during the packaging process could inadvertently damage the sterile barrier. . FDA Determined Cause: Packaging Process Controls

Manufacturer Reason for Recall: Firm is recalling sterile-packaged implants and instruments packaged in six different package configurations due to packaging design verification test failures. Specifically, multiple test samples from each of the six configurations failed simulated distribution and shipping testing when the devices either breached inner or outer package trays or seal integrity was lost. .

FDA Determined Cause: Packaging Process Controls Zimmer

Maintain Sterility Until Point of Use / Expiry • Some supplies and or devices have expiration dates and degrade over time • Make sure you understand your product and packaging expiry and data to support it.

• Test at worst case conditions • within the validated window of manufacture • Worst case configuration of device- • most fitments, heaviest joint, most pieces • Largest, smallest sterile barrier system • size and/or seal area

NOTE: Worst case is bad enough. Don’t test for conditions that don’t exist Do enough testing with enough units.

• Accelerated Aging – A protocol to determine the affects of time on a package/product. – Humidity not part of the model

• Environmental Challenge – Goal to determine sensitivities – Can be extreme

Q~10~=2

Arrhenius equation = effect of increasing temperature on homogenous 1st order reaction.

Accelerated aging – increase of 10 degrees Celsius doubles reaction rates.

Don’t get carried away!

• Tyvek is inherently clean peeling and low linting • Coated Medical grade papers are designed to minimize particulate generation • Clean peel minimizes the risk of introducing particulates into a clean environment.

5• Allow aseptic presentation – Allows for sterile handling – Peelable opening features allow for sterile presentation – Outside of package is not sterile – Must peel easily but demonstrate a good seal

Package development is an involved task. Don’t forget your packaging supplier.

Questions?