Steris on how to rise to sterilisation challenges

^{Vapourised Hydrogen Peroxide (VHP) sterilisation challenge testing for COP (cyclo olefin polymer) container material, by Juha Mattila, Steris Finn-Aqua.}

Low temperature terminal surface sterilisation by Vapourised Hydrogen Peroxide (VHP) is becoming more common in pharmaceutical and medical device manufacturing applications. This development can be seen with sensitive drug products, such as ophthalmic injectables, or other heat or radiation sensitive medical devices. VHP is compatible with most plastic materials used in the industry, but there may still be some knowledge gaps particularly when dealing with novel applications or when a specific new material is being introduced.

A terminal surface sterilisation process must not alter the device or packaging properties, to ensure that biocompatibility, device integrity, usability, and/or product shelf life are not compromised. Exposure to sterilant should be controlled and maximum allowed processing temperatures not exceeded. Also, the sterilising agent must not penetrate inside a primary container of a drug delivery device.

Cyclo olefin polymer (COP) is used as material for syringes and other drug delivery devices for prefilled drug primary containers, syringe barrels, vials and bottles. COP syringes have specifically been successful when employed with sensitive protein drugs. Because of this, there have been several inquiries about compatibility of COP syringes and VHP (VH₂O₂) for use in drug delivery devices’ surface terminal sterilisation process. One of the concerns has been to understand if VHP vapour can in any way penetrate the syringe wall - as it was suspected that it might be possible for oxygen (O₂) to penetrate due to lower oxygen barrier properties of COP and considering that VHP breaks down to water vapour and oxygen during sterilisation exposure. Such application-specific material penetration studies for VHP and COP were not available.

Steris Finn-Aqua and Zeon agreed on a case study and developed a sterilsation challenge test plan. This plan included the selection of a suitable COP container for testing, developing a low concentration detection method for any hydrogen peroxide residual in WFI (water for injection) filled sample containers, and programming a series of sterilisation challenge test cycles and conditions to achieve sufficient and representative VHP sterilant exposure under deep vacuum.

An analysis method by spectrophotometry using Toluidine Blue to determinate low concentrations of hydrogen peroxide in WFI water samples was developed by VTT Expert Services, Finland. The calibration curve created for the analysis method provided a detection limit of 100ng/ml (ppb).

Relatively large volume COP containers (Zeonex 690R, V=100 ml, D_i=32,5mm, L=120mm, wall s=1,3mm) were selected to expose as large a surface area of material to VHP sterilisation as possible, to ensure penetration testing to be representative. A total of six container tubes were used in the sterilisation exposure testing such that a set of two tubes were exposed to one, three, and five times the exposure time of a VHP sterilisation cycle. Test containers were placed in the chamber without any packaging. Positive and negative control samples were also provided to the laboratory as part of sampling.

Each container was filled with 50ml of WFI and the tube ends were sealed with applicable glue, rubber cap and tape to avoid leaking inside. Vaprox 35% hydrogen peroxide sterilant was used in the VHP terminal steriliser (Steris VHP LTS-V-91515-S7) of 2.0m³ chamber volume including a mock-up load for creating representative cycle conditions.

The most challenging sterilisation exposure cycle was configured to be equal to five consecutive deep vacuum (4 mbar), low temperature [+30…32 °C] sterilisation exposures resulting in a total of 90 injection pulses, 87g of hydrogen peroxide in vapour state, 180 minutes of exposure time and 5h 29min of total cycle time.

Presence of hydrogen peroxide in post-exposure spectrophotometric analysis of the WFI samples was below the spectrophotometric analysis detection limit of 100ng/ml. Measurements by a Draeger hand-held peroxide sensor device were also taken directly on the tube surfaces right after each cycle’s end. The highest measured surface reading was 0.1ppm. All other measurements were below detection level of the sensor. No discolouration was detected either. Low levels of surface residue on containers after the sterilisation cycle indicate that COP’s hard and glass-like surface does not absorb significant peroxide.