Sterility is the absence of viable micro-organisms, as defined by a sterility assurance level equal to or less than 10– 6. Sterility is a critical quality attribute for a wide variety of human and veterinary preparations, including but not restricted to:
— preparations required to be sterile due to their route of administration, such as parenteral, ophthalmic and intramammary preparations, and some inhalation, irrigation and intrauterine preparations;
— preparations applied to severely injured skin, such as semi-solid preparations for cutaneous application.
The achievement of sterility for any one item in a population of items submitted to a sterilisation process can neither be guaranteed nor demonstrated. It is essential to study the effect of the chosen sterilisation procedure on the product (including its final container) to ensure its effectiveness and the integrity of the product, and to validate the procedure before it is applied in practice. Failure to follow meticulously a validated process introduces the risk of a non-sterile and/or deteriorated product.
Sterile products are prepared under appropriate conditions and are packed in suitable containers. It is recommended that the choice of container permits application of the optimum sterilisation process for the product. The container and closure system are required to maintain the sterility of the product throughout its shelf life.
Sterilisation process conditions are chosen to achieve the highest level of sterility assurance compatible with the drug product and, wherever possible, a process in which the product is sterilised in its final container (terminal sterilisation) is chosen. When a fully validated terminal sterilisation method by steam (moist heat), dry heat or ionising sterilisation is used, parametric release (i.e. the release of a batch of sterilised items based on process data rather than submission of a sample of the items to sterility testing) may be carried out, subject to the approval of the competent authority. If terminal sterilisation is not possible, aseptic assembly or filtration through a bacterial retentive filter is used. Wherever possible, an appropriate additional treatment (e.g. heating) of the product in its final container is applied to further ensure the sterility assurance level.
Requirements for the use of biological indicators for validation of sterilisation processes are given in general chapter 5.1.2.
The present general chapter provides guidance on conditions, validation and control of sterilisation processes. The methods described here apply mainly to the inactivation or removal of bacteria, yeasts and moulds. For biological products of animal or human origin, or in cases where such material has been used in the production process, it is necessary to demonstrate during validation that the process is capable of the removal or inactivation of any relevant viral contamination. Further guidance is provided in general chapter 5.1.7. Viral safety.
The efficacy of a sterilisation process is dependent on its nature, the processing conditions (e.g. time, temperature, moisture), the pre-sterilisation microbial contamination and the formulation of the product. The inactivation of micro-organisms by physical or chemical means follows an exponential law and hence there is always a non-zero probability that a micro-organism may survive the sterilisation process.