There are many challenges that arise from choosing steam sterilisation. Lee Simpson, Medical Device Sterile Product Specialist, High Edge Consulting highlights some key considerations when designing cycle development for validation.
Even as the “grandmother” of sterilisation, steam is still a popular choice for the medical device industry. It is still widely used in virtually every central sterilisation department throughout the UK National Health Service, for example. Using steam has its benefits, but it also has its challenges. Steam has the benefits of being very effective and relatively cheap and quick. Saturated steam under pressure is also effective against a wide range of microbes including spores.
The regulatory framework defined in Europe demands that the routine validation steps are followed: Installation qualification (IQ), operational qualification (OP), and performance qualification (PQ). But nestled away inside ISO17665: (Sterilisation of health care products – Moist heat – Part 1: Requirements for the development, validation and routine control of a sterilisation process for medical devices) is the requirement for sterilisation development.
Steam is not suitable for many materials due to the high temperatures and pressures involved. To maintain sterility, the devices require packaging that acts as a sterile barrier after the sterilisation process. This means that the cycle has to be suitable, not only for the devices, but also for the associated packaging. To achieve sterility is a relatively routine task, however, the marketing department does not usually like the detrimental outcome to the physical branding displayed on the packaging.
Steam is not suitable for many materials due to the high temperatures and pressures involved
Steam is pretty harsh on packaging as it can cause shrinkage of paper-to-paper packaging and also creases in the adhesives joining the layers of the packaging or the labels. Sometimes the device itself is affected because some materials discolour when exposed to high temperatures for long time periods. Thus, the effects of the cycle on the product and packaging needs to be considered as a design input for the development of the sterilisation cycle.
ISO17655-1 focuses on the use of moist heat to sterilise using the following technologies: saturated steam venting systems; saturated steam active air removal systems; air steam mixtures; water spray and water immersion. The first three listed are typical for use in autoclaves and follow a typical autoclave cycle:
- Air removal
- Attaining temperature
- Sterilisation
- Drying
- Cooling
The above is suitable for impermeable materials, non-impermeable materials, solids, liquids and cycles that are mixed. It also states that the manufacturer is responsible for the development of the process and has to provide guidelines/instructions for the operation and validation of the process. In this part of the standard it also details the conditions that affect the process. ISO17655-2, discusses the application of part 1 in detail.
So when does cycle development occur? Within the typical V-model, I suggest that cycle development occurs once the IQ and OQ are completed (see Figure 1). This is due to the Parental Drug Association’s definition that cycle development is “the process of determining the physical parameters of the sterilisation cycle that will be used to sterilise a particular load pattern.” Thus, the steriliser must be loaded in such a way as not to hinder the sterility process or the appearance and functionality of the devices. To determine this load pattern the steriliser needs to be in-situ and operational.
There are some simple rules to follow in cycle development, which are:
1. Plan the time for the cycle development. You do not want the operational department harassing you for the equipment and then finding out that it does not work.
2. Cycle development starts in the design phase with the choice of the materials of construction and packaging.
3. A suitable volume of product is required for the development of the cycle. In most cycle development projects, the same product could be used more than once, as long as the product remains in a representative state of the original loading.
4. The correct equipment is required to record the data.
5. Always involve the marketing team to establish that the aesthetics of the product are acceptable.
6. Have agreed acceptance criteria.
During air removal (sometimes called pre-conditioning) to achieve a partial vacuum, the presentation of the device and its packaging in the load needs to be considered. The strength of the packaging seal is important but it is also crucial to ensure that it remains intact. In the presence of mixed loads it is important to ensure that there is a gas pathway to ensure that air can be removed. This usually involves clever presentation in the load pattern. Having two impermeable materials back to back should be avoided, unless there is sufficient air movement from either a stopper, or tubing.
During a hybrid mix of moist steam and air cycle it is the same principle. For example, in the case of syringes, a gas pathway is needed that is not going to cause the stopper or syringe cap to explode off the syringe. Gas usually traverses down the plunger and, thus, most plungers have more than one lip to attain a pressure difference throughout the device. Gas always takes the path of least resistance so it will travel down the plunger into the chamber for removal.
In the case of syringes, a gas pathway is needed that is not going to cause the stopper or syringe cap to explode off the syringe
The attaining temperature phase is where a full vacuum is reached and steam is introduced into the chamber. The way the load is presented has to be considered, as well as the “thermal loading” of the load. This is the amount of energy needed to be introduced into the steriliser to reach the sterilisation temperature. If the thermal load is greater than the normal load designed for the autoclave, then it will be necessary to add additional pulses, or introduce the steam at a quicker rate into the chamber.
Additional pulses bring challenges to maintaining the sterile packaging, and also to the physical condition of the device. During this phase of the cycle, a sterile wound dressing pack acts like a set of bellows – expanding and contracting with the pulse. This adds strain to the packaging integrity. If in a mixed load and the device is a prefilled syringe, then the materials of construction will start to expand during the pulsing. This allows the functionality of the device to be compromised. The materials of construction must be able to expand and contract like a set of bellows.
Introducing steam more quickly into the chamber is usually the safest option, but that in itself brings its own challenges. Quickening the addition of steam to the load usually means that the saturation of the materials happens more quickly, which means additional drying is required later on in the cycle.
Attempts should always be made to design the cycle up front to meet the required sterilisation cycle times
The greater thermal loading of the steam into the chamber also usually results in a greater risk of “Super heat” being generated during sterilisation. Super heat is where steam is converted into temperature as the energy of the steam exceeds the pressure equilibrium within the chamber. This usually results in a non-compliant sterilisation cycle. Steam speed can be controlled by increasing the length of the pulse and by maintaining the steam flow as a constant, i.e. the sterilisation phase exceeds the temperature range of sterilisation (>134°C to 137°C).
Considerations of the cycle during the sterilisation phase should be kept to a minimum. The cycle has to meet the temperature profile defined in the standards for the required duration of the sterilisation phase. It is, therefore, advisable to leave this section of the cycle well alone. Attempts should always be made to design the cycle up front to meet the required sterilisation cycle times.
However, if issues arise during this phase there is a limit to what can be done. The main problem is maintaining the equilibrium of the sterilisation temperature and the pressure required to sterilise the device. This equilibrium is dependent on how the autoclave controller responds and the location and capability of the proportional valve – the valve where steam leaves the chamber. This means, if super heat occurs, that steam needs to be allowed to leave the chamber. The proportional valve will be adjusted to allow more steam to escape the chamber.
The general problem of the drying phase is that the phase is either not long enough or effective for the thermal loading of the chamber, resulting in wet devices and packaging once the cycle has finished.
Drying is achieved by pulsing the chamber with air. This pulsing is not as strong as the pulsing used to achieve sterilisation, however, with wet paper packaging it is easier to rip and penetrate the sterile barrier during the bellowing effect. Thus the positioning of the devices in the load is critical to allow air penetration and a gas pathway. To improve the drying phase, the number of pulses can be increased and the speed of the air to be introduced can be increased. However, it is usually the addition of an extra pulse or the change in the length of the pulse that is used to improve drying of the load.
To summarise, cycle development needs to cover the following:
- Compliance requirements – but there are a limited number of things that can be done during the cycle development process.
- Changes made to the cycle that must be assessed against the validated state established during IQ and OQ.
- The most important factor – the acceptance criteria.
