Monitoring the situation: independent monitoring for industrial steriliser cycle

Juha Mattila, director, sterilisation technologies, STERIS Life Sciences, discusses how the company is developing technologies that improve patient care – independent monitoring for industrial VH202 steriliser cycle control and monitoring.

Vapourised Hydrogen Peroxide (VHP) – or VH2O2, is playing an increasingly important role for today’s biopharmaceutical and medical device industry manufacturers. This is especially true when considering a sterilisation modality, feasible for temperature and/or radiation sensitive, packaged single-use devices. Such products include hip and knee implants, stents, cardiovascular type implantable devices, subcutaneous patches, and combination devices such as a pre-filled syringe designed to administer a sensitive drug, such as ophthalmic injectables for macular degeneration disease of the eye.  

STERIS manufactures VH2O2 steriliser equipment for sterilisation of re-usable medical devices in healthcare setting, and industrial sterilisers for sterilisation of single-use medical devices in biopharmaceutical and medical device manufacturing facilities. The first VH2O2 sterilisers for industrial use were introduced by STERIS over 20 years ago. 

VH2O2 is compatible with most materials and applicable for surface sterilisation at low temperatures of 28-50 °C [82-122°F]. A benefit of VH2O2 sterilisation is the absence of any toxic residuals or byproducts, as hydrogen peroxide sterilant breaks down into water vapour and oxygen.  

A risk-based approach to sterilisation process is required. The recently published EU Annex 1:2022 adds emphasis to this and sets more specific requirements for manufacturing of medicinal products in Europe and globally.  

Control over a sterilised production batch is achieved by routine monitoring. This includes monitoring the process and the inactivation of process challenge devices placed on the product load being sterilised.  An application-specific external process challenge device (ePCD) is developed and validated for the process and then used to verify successful sterilisation of production batches. A process challenge device is a combination of a biological indicator of known high resistance (Geobacillus Stearothermophilus), and an item providing a defined resistance to a sterilisation process that yields an equal or higher resistance than the product being sterilised. 

Sterilisation process is required to be controlled, monitored, and independently verified. Resulting continuous risk-based evaluations to improve process safety in the industry, independent monitoring has been introduced in equipment standards such as EN 285 for steam sterilisers and EN 1422 for ethylene oxide sterilisers.  

ISO/TS 22421 sets common requirements for steriliser equipment and includes general guidance for independent monitoring. Having a specified and validated independent monitoring of process variables in place can be instrumental in considerations for parametric release of production batches. 

VH2O2 sterilisation is a well-recognised process as evidenced by the recently published VH2O2 specific standard ISO 22441 - Sterilisation of health care products – Low temperature vapourised hydrogen peroxide – Requirements for the development, validation, and routine control of a sterilisation process for medical devices. Currently, CEN is also developing the standard specific to VH2O2 equipment requirements (EN 17180). Currently it is estimated to be published in 2024.  

A modality-specific industry standard results in the ability to be more specific with the requirements and risk mitigating approaches that enable continuous improvement of processes for the industry.  

ISO 22441 sets general requirements for the process but also calls out for control and monitoring and defines the main process variables: 

• time (intervals and setpoints) 
• temperature 
• VH2O2 concentration (measured directly or indirectly) 
• pressure  

Sterilisation process 

An industrial VH2O2 steriliser process is based on vaporising liquid hydrogen peroxide sterilant (H2O2), typically of 35% concentration and delivering into the chamber by vacuum. Vapourised hydrogen peroxide is delivered in a non-condensing dry vapour state into a production scale chamber of up to 9,000-litre volume. Deep vacuum pulses of 4-10 mbar [3-7 Torr] and chamber fan circulation are used to ensure the hydrogen peroxide sterilising agent reaches all locations within the load and devices to be sterilised. After sterilisation, the hydrogen peroxide sterilising agent is removed from the chamber and load by aeration, with in-line catalysing of exhaust effluent to destroy remaining hydrogen peroxide. 

Temperature 

Achievable maximum VH2O2 concentration is dependent on chamber temperature. Cycle temperature is unidirectional only, meaning that the process has a minimum temperature to reach prior to cycle commencing to the sterilisation phase. The cycle temperature typically increases during the entire cycle, and this results in slightly increasing the VH2O2 concentration during the sterilisation phase to maintain the defined relative humidity (RH%) setpoint. 

VH2O2 concentration 

Equally important as temperature is controlling the VH2O2 concentration to ensure consistent and repeatable sterilisation efficacy, and optimal total cycle profile in general. The VH2O2 injections increase chamber humidity, and the process is controlled by the steriliser via a relative humidity sensor (RH) that has a specified set point (RH%) resulting from cycle development and process validation. The purpose of the RH-sensor is to control reaching and maintaining VH2O2 concentration during the sterilisation pulses.  

Pressure and time 

The chamber pressure sensor is assigned to control the vacuum level to a defined set point (4-10 mbar level). The exact pressure and hold time parameters for each specific sterilisation application are determined during validation activities.   

Independent monitoring 

The STERIS VHP LTS-V steriliser independent control and monitoring design adds a reference load temperature sensor and a reference chamber pressure sensor to the chamber. Measurements from these devices are transferred to an independent recording device. The total consumption of hydrogen peroxide during the cycle is monitored by measuring the total injected volume of VH2O2 per cycle from the liquid hydrogen peroxide reservoir that feeds the VH2O2 vaporiser. This value is transferred to the recording device for evaluation (see VH2O2 reference level sensor in Diagram 1). 

The control sensor measurements are taken to the PLC that controls the chamber process and to the recorder. The reference sensor measurements are directly taken to the recorder. The recorder compares these measurements and their specified ranges and establishes if any deviations exist. These deviation values are sent to the PLC where all deviation alarms are recorded and printed in the batch report for batch evaluation. 

Independent monitoring of a sterilisation process is designed to improve process control reliability and confirm that required means are provided to ensure an effective cycle. 

Along with the long application history, regulatory approvals, and having the latest developments of industry standards in place, VH2O2 sterilisation is proven to be a comprehensively established sterilisation modality that can safely be implemented to a medical device sterilisation application.