Sterilisation methods

Pharmaceuticals for injection must be presented in a sterile form. Sterility may be achieved by filtration through 0.22 pm filters under aseptic conditions, or by steam, dry heat, radiation or gas sterilisation methods, which may be applied to packaged products. Irrespective of the method, the process must be validated and monitored to assure its effectiveness. As discussed in Chapter 2, this is an example of a process that cannot be assured by verification testing because of its destructive nature. 

EMEA/CVMP/065/99 final Decision trees for the selection of sterilisation methods (February 2000)... 

The European agency for the evaluation of medicinal products. In Decision Trees for the Selection of Sterilisation Methods London, 1998. 

Sterile products must be manufactured in separate enclosed areas under the supervision of a microbiologist. The sterilisation method has to be scientifically proven, validated and qualified. 

From here on this chapter expands the properties of various plastics, the means by which certain physical and chemical characteristics can be identified and quantified, together with the constituents which may be found in a plastic. The converting processes may contribute other factors relevant to the selection and clearance of a plastic pack. The chapter concludes by reference to sterilisation methods and references. (The next chapter places particular emphasis on the clearance of a plastic pack , and should be read in conjunction with this section.)... 

Although sterilisation methods may initially appear to be well documented, there is a need to review how each may change both the physical and chemical properties of packaging materials, containers and components. 

All sterilisation processes should be validated. Particular attention should be given when the adopted sterilisation method is not described in the current edition of the European Pharmacopoeia, or when it is used for a product which is not a simple aqueous or oily solution. Where possible, heat sterilisation is the method of choice. In any case, the sterilisation process must be in accordance with the marketing and manufacturing authorizations. 

A wide variety of equipment is used for chromatography, and in general such equipment should be dedicated to the purification of one product and should be sterilised or sanitised between batches. The use of the same equipment at different stages of processing should be discouraged. Acceptance criteria, life span and sanitization or sterilisation method of columns should be defined. 

Polyether-imide (PEI) is an amorphous thermoplastic, with an excellent balance of physical properties and dimensional stabilities. PEI can be nsed with the fnll spectrum of sterilisation methods. Surgical probes that are subjected to repeated cleaning and sterilisation are their typical preferred application as a medical plastic. 

Raw materials Containers Human resources Occupational safety and health Premises Equipment Basic operations Sterilisation methods Aseptic handling Quality requirements and analysis... 

When formulating aqueous ophthalmic preparations attention should be given to osmolality, pH, solubility, chemical interactions, stability of the active substance, together with viscosity and the choice of a preservative. Sterility is of critical importance and therefore the most appropriate sterilisation method must be chosen. 

Sterile cutaneous preparations undergo sterilisation in the final container if possible. Many active substances, base preparations and package materials for cutaneous preparations however are not resistant to the common sterilisation methods, see also Sect. 30.8. If sterilisation in the final container is not possible, cutaneous dermal preparations should be prepared aseptically and packaged in sterile packaging materials, see Chaps. 30 and 31. On the label of sterile cutaneous preparations the word sterile has to be mentioned. After opening, these preparations can only be stored for 24 h. 

Components of parenteral solutions (active substances, excipients, intermediates and packaging material) should be routinely tested for bioburden and bacterial endotoxin level to ensure they are not adding an excessive microbial load. Bioburden is usually determined on the unfiltered bulk solution. Testing of filtered bulk parenteral solution either before or after filling into the final container may be done by comparison to the previously tested unfiltered bulk solution. Initial bioburden and endotoxin monitoring should be conducted to establish appropriately designed and sized terminal sterilisation methods such as filtration/aseptic filling or terminal heat treatment (see Sects. 30.5 and 30.6). Bioburden is also used as a parameter to evaluate process control. 

Adapting the formulation may allow the application of a more reliable sterilisation method. An example is talc powder used in pleurodesis. The easiest and cheapest sterilisation method for talc powder is prolonged dry heat exposure. But this sterilisation method is more difficult to validate than autoclaving. Instead of pure talc powder, a talc suspension in 0.9 % NaCl solution was prepared and autoclaved [45]. 

The chemical stability of the active substances is important with regard to the choice of sterilisation method and the pH. For example during sterilisation chlorhexidine degrades to 4-chloro-aniline and other related substances. By adjusting the pH of the solution to 5 this degradation remains within acceptable limits (4-chloro-anUine < 0.5 %, total other related substances < 3.5 %). 

Sterilisation by means of ionising radiation of pharmaceutical preparations is not allowed in a number of countries. Many active substances and raw materials are decomposed by the doses required for sterilisation. Some polymers become brittle and glass may become discoloured. For these reasons there is only limited application for this sterilisation method for pharmaceutical preparations. Radiation sterilisation is however widely used in the medical device industry. 

This chapter discusses sterilisation methods and equipment for the sterilisation of medicinal products, medical devices and utensils. Sterilisation is an active, validated process in order to kill micro-organisms. It is the most critical step in the preparation of sterile products. The achievement of the absolute state of sterility cannot be demonstrated, sterility can be defined only in terms of probability. 

Classical sterilisation techniques using an autoclave and saturated steam under pressure, hot water or dry heat are practical and reliable. Other reliable sterilisation methods include membrane filtration, ionising radiatirm sterilisation (gamma and electron-beam radiation) and gas sterilisation (ethylene oxide, formaldehyde). Sterilisation equipment (autoclaves, membrane filters, and other sterilisers) is often used in industrial manufacturing, in preparation in pharmacies, and in other healthcare establishments. Standard sterilisation processes are described in the Ph. Eur., in other current Pharmacopoeias, in ISO standards and National guidelines. 

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