Feasibility testing, Cycle development and Validation

Guidance for VHP Low Temperature Surfaces Terminal

Sterilization Applications Juha Mattila

STERIS FINN-AQUA Juha.Mattila@steris.com

Main topics

• VHP Low Temperature Surfaces Sterilization process principle and properties

• Types of products and applications and implementation to packaging process • Product feasibility testing

• Cycle development

• Validation guidance

VHP basic properties • VHP = Vaporized Hydrogen Peroxide • Low temperature dry vapour process, below dew point • Used for low temperature sterilization and room / surfaces decontamination • Destroys full spectrum of biological contaminants • Breaks down to water and oxygen

• When VHP Low Temperature Sterilization process? -In case conventional terminal sterilization methods are not applicable

STEAM GAMMA ETO

In-House medical device products (e.g.

implants)

Surface Sterilization of pre-filled sensitive drug

delivery devices.

Patient Care-Lumen and Non-Lumen Devices

VHP deep vacuum sterilization – types of applications

• For temperature / radiation sensitive drug products in delivery devices

• Sterilized surfaces of device exterior and package interior (example: ophthalmic, other injectable products)

• Pharmaceutical manufacturing applications related to aseptic packaging process

Applications

Packaging process implementation example

VHP Low Temperature Surface Sterilization Process

1) Pre-conditioning 2) VHP Exposure 3) Post-conditioning*

*) ”Post-conditioning” is also referred to as ”aeration”

Process graph with process steps

• Typical process temperature range +28…40 °C

• Deep vacuum level typically 1…10 mbar

• Typical cycle time 2…4 hours, depending on product, load config and materials

Typical packaged device and VHP contact scenario NO penetration to drug container(s)!

Sterilization of blister package interior and device and its components’ external surfaces VHP vapor out

through Tyvek®

during post-conditioning (vacuum pulses)

Specific passage-through, or dead-leg location

VHP vapor in through Tyvek®

layer in the back

Understanding of VHP sterilization exposure with different materials and conditions under deep vacuum:

• VHP general plastic material compatibility is very good • Softer plastic materials absorb VHP (or other sterilant) • Harder surface plastic materials absorb significantly less

• Stainless steel and aluminum compatibility is very good

• Absorption is not penetration through the material wall thickness • VHP does not penetrate through the material • Tyvek is a layer material specifically designed for vapor (steam or other)

penetration – in and out • Cellulose materials (paper, pulp, wood) break down peroxide to oxygen and

water • Specific metals (copper, platinum) act as catalyzers to VHP, breaking

peroxide down to oxygen and water

Application example – Mixing device

Application examples – Vials & syringes

Application example – packaged syringes load of a smaller production size unit

Products by category

Wrapped / Packaged vials

Syringes, Hyaloronic acid based products

Syringes, Ophthalmic drug products

Wound Care Dispenser Devices

Mixing Devices (combining two components prior to injection)

Packaged towel products, other packaged products

Typical product applications:

Implementation steps to packaging process

• Feasibility testing before project • FAT & Load cycle development • IQ/OQ (SAT) ⇒ Basis of Validation

• Medicinal manufacturing license for handling drug product samples!

FEASIBILITY Testing objectives: • Product tolerance with vacuum • Allowable vacuum level • Plunger movement • Physical failure(s) seen by naked eye (i.e. fracturing etc.) • Package failure(s) seen by naked eye (i.e. seam failure etc.) • Sterilization cycle result • Penetration into the blister package for sterilizing outer surfaces of the product • Ingress test (quick test) • Operator safety - residuals in the end of the cycle (1 ppm 8 hours, 3 ppm 15 min) • Residuals inside the blister package Testing verification: • Chemical and Biological Indicators • Peroxide quick test strips for ingress • Peroxide residual ppm readings of load and packages (low ppm range sensor, lab tests if applicable)

CYCLE DEVELOPMENT Objectives: • Cycle optimization (cycle time) • Using the designed actual unit, carts, full load of products • Basis for validated production cycle • Verify equipment and process in practice • Sterilization cycle result testing for the full load • Operator safety - residuals in the end of the cycle (1 ppm 8 hours, 3 ppm 15 min) • Residuals inside the blister package Testing verification: • Chemical and Biological Indicators • Peroxide residual ppm readings of load and packages

Sample load(s) used => Cycle tests with actual production unit => Initial optimization and parameters to benefit the final validated cycle

Biological indicators prove sterilization efficacy Chemical indicators show VHP coverage in load and chamber (Full color change)

• ISO standard for process validation not available • ISO 14937:2009 – Sterilization of health care products - General

requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices

• => To be used for basis of validation + supporting ISO TS (technical standards referenced with the main standard) – e.g. probability study

• In some instances ISO 11135 has been used as guideline • Application specific validation always required • USP 1229.11 - Defining Vapor Phase Sterilization in effect since August 1st,

2015 (includes hydrogen peroxide, peracetic acid, formaldehyde and glutaraldehyde)

VALIDATION GUIDANCE

Defined load configurations for cycle repeatability

VALIDATION GUIDANCE • Probability study of process for SAL 10-6 (half-cycle – full cycle) • Empty chamber, half load, full load • Bacillus Stearothermophilus 106 biological indicators • Controlled process (humidity - concentration, temperature, pressure) • Temperature control merely for control of maximum allowed process

temperature exposure • Repeatability (load configuration, repeatable process, parameter limits • Product integrity (materials, stoppers, plunger movement) • Measure residual ppm’s in the load, inside package, product surfaces • Residual ppm level: < 1 ppm • OHSA requirements for operator use (1 ppm for 8 hrs, 3 ppm for 15

minutes)

TAKEAWAYS: • Product and materials feasibility testing to verify suitability • Plastic materials and stainless steel / aluminum are generally well

applicable • Understanding the VHP process and conditions, implementation,

applications • Understanding VHP exposure scenario under deep vacuum

conditions • Cycle development for optimal cycle, using actual load and unit • Validation considerations and guidance – ISO14937 related • Step-by-step approach in implementation

THANK YOU! QUESTIONS?