feasibility testing, cycle development and validation guidance for vhp low temperature surfaces...
TRANSCRIPT
Feasibility testing, Cycle development and Validation
Guidance for VHP Low Temperature Surfaces Terminal
Sterilization Applications Juha Mattila
STERIS FINN-AQUA [email protected]
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?