Sterilisation processes

Validation and Foutine Monitoring of Moist Heat Sterilisation Processes, ISO 11134, International Standards Organization, Geneva, Switzerland. 

EC verification provides an alternative to the model of establishing a certified production QA system. Independent testing of either all devices, or a statistically representative sample of each batch, is conducted by or on behalf of the Notified Body, which then issues a certificate of conformity for the tests conducted. This is not a popular option due to the costs involved. The procedure is not capable of providing adequate assurance as to the sterility of devices. Instead, an assurance of sterility must be based on the application of a production QA system to the sterilisation process. 

For low-risk devices the manufacturer may make a declaration of conformity with the essential requirements on the basis of a self-assessment, without any input from a Notified Body. In the case of Clas s I devices that are sterile or have a measuring function. Notified Body involvement is required, to provide assurance as to the effectiveness of the sterilisation process or the meteorological traceability of values as appropriate. 

Jung, A. and Fryer, P.J. (1999). Optimising the quality of safe food Computational modelling of a continuous sterilisation process. Chemical Engineering Science, 54 717-730. 

The various elements of the ISO standards for a validation programme of a radiation sterilisation process are shown in Fig. 6.11. 

Sterilisation—type of sterilisation. Processes and validation. Control of sterility. Control of residual ethylene oxide, ethylene chlorohydrin, ethylene glycol. 

Different processes are applied to achieve this purpose, depending on the foodstuff involved. The technical possibilities available are pasteurisation and sterilisation processes, sterile filtration and the application of modified atmosphere packaging (MAP). The foodstuffs are chemically treated with preservatives. The application of ionising radiation is also permitted in some countries. 

A pilot study on the heat sterilisation process of the sediment material was performed to evaluate the losses of CBs. From the results it was concluded that the heat treatment has to be carried out at ca. 120°C over a period of 2 h in order to have the least effect on the CB content. Immediately after sampling, the sediment was air-dried at 40°C over a period of several weeks with continuous churning up and removal of larger objects. The dried sediment was then sieved (pore size 2 mm) and jet-milled for a particle size of less than 125 pm and heat sterilised at 120 C for 2 h, homogenised in a 250 L multi-purpose mixer during semi-automatic filling of bottles. The material was finally packed in 4400 bottles, each one containing 40 g. 

Packaging for sterile products must be effectively contained and sealed to prevent microbial contamination, and must be robust enough to withstand any sterilisation process required. The sterilisation process can affect the leaching of components from the container into the product or affect the physical properties of the container. For example, autoclaving can soften plastic containers, and gamma irradiation can cause certain polymers to cross link. 

Suspension products may pose challenges to the formulator in manufacturing to achieve a sterile product. The possibilities of either degradation or morphological changes occurring during the sterilisation process exist and must be prevented. 

It will be necessary to conduct preliminary feasibility studies to establish an acceptable and effective method for sterilisation of the product. There is a clear responsibility with the manufacturer to provide evidence to the regulatory agencies that the product can or cannot be terminally sterilised. Preformulation studies will indicate whether the candidate drug and proposed formulation can withstand the sterilisation process using small samples of product. 

Sterilisation is the finite method for microbial control and can be achieved either by sterilising each component (product and packaging materials) followed by assembly, i.e. aseptic processing, or by a terminal sterilising process which involves both product and pack. The latter is the preferred method as it entails less risk of a non-sterile product being produced. 

Virtually all sterilisation processes impose some hazard or risk of adverse effects on the packaging material, and they all need study before they can be pronounced as com pletely satisfactory. Those processes which may be critical to a particular material will be reviewed in great detail in the respective material section. 

Check if washing and sterilisation process (i.e. autoclaving of stoppers) generates any particulate matter. 

One of the early restrictions with plastic and pharmaceutical usage was associated with difficulties related to suitable sterilisation processes. The processes which can now be used include all conventionally available, i.e. 

This is not recognised by the BP or USP as a formal sterilization process. UV light is basically a surface sterilising process and is used in some sterile (class 1) areas to reduce any airborne contamination. 

The British Pharmacopoeia 1980 included this as a sterilising process for aqueous products where the drug entity exhibits thermal instability but will withstand up to 100 °C for 30 min. The process was subsequently excluded from the BP 1988. 

It can therefore be concluded that all plastics are capable of sterilisation but need the selection of the most suitable process. Plastics will not support the growth of microbial contaminants unless the surface is wet or a high storage RH is involved. The bioburden may be increased by certain particulates, particularly if these consist of materials which will support growth. Material cleanliness and low particulate levels are therefore a prerequisite for a fully effective sterilisation process. 

It can be concluded that a pack may be affected by most of the sterilisation processes hence thorough testing is essential in terms of possible changes in physical and chemical properties and appearance. Loss of preservatives may also be critical at a sterilisation stage. 

Resistance to sterilisation process (dry heat, moist heat, irradiation, UV, etc.). 

The basic pharmacopoeial accepted sterilisation processes include ... 

---