Heat sterilisation

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

The production-scale fermentation unit, with a projected annual capacity of over50,000 tonnes was fully commissioned in 1980. The bioreactor (Figure 4.8) is 60 m high, with a 7 m base diameter and working volume 1,500 m3. There are two downcomers and cooling bundles at the base. Initial sterilisation is with saturated steam at 140°C followed by displacement with heat sterilised water. Air and ammonia are filter sterilised as a mixture, methanol filter sterilised and other nutrients heat sterilised. Methanol is added through many nozzles, placed two per square metre. For start-up, 20 litres of inoculum is used and the system is operated as a batch culture for about 30 h. After this time the system is operated as a chemostat continuous culture, with methanol limitation, at 37°C and pH 6.7. Run lengths are normally 100 days, with contamination the usual cause of failure. 

Tyrosine, tryptophan and tetracyline are filter-sterilised to prevent decomposition by heat sterilisation. 

Dry heat sterilisation is used for equipment that can withstand high temperature and dry heat but cannot withstand wet or steam autoclave. This method is often used for glassware as it dries and sterilises in one operation. The pipets must be wrapped in dustproof aluminum foil or placed in metal pipette cans. The can lids are removed during heating and replaced after sterilisation, that is before any dust can get in the can. Disposable items are not recommended for dry heat sterilisation. This method may only be good for permanent reusable glass pipettes. 

Neomycin sulphate may also be heated at 110°C for 10 hours, during dry-heat sterilisation, without loss of potency, though some degree of yellowing is apparent298. 

In summary, these experiments show clearly that heat sterilisation induces an equilibrium between the groups Gl, G2 and G3,but that there is no equilibration between the individual component within each of the groups. For verification of these correlations, we utilized four model compounds with defined stereochemistry (Fig. 9) and performed HPLC analysis of aqueous solutions. 

During the heat sterilisation a separation of two layers can be observed. Shaking of the ampoules during cooling gives homogeneous clear solutions. 

Packaging, medical supplies, lighting Food packaging, automotive trim, toys, bottles, films, heat-sterilisable containers... 

Certain items, such as balanced salt solutions and versene which are heat-stable, are generally sterilised by autoclaving, but the majority of organic materials used in cell culture are filter-sterilised. For heat-sterilised materials it is generally sufficient to rely on a sterilisation indicator which should be included with each batch of materials being sterilised. Often autoclave tape is sufficient if used on each packet, but for solutions and larger containers, e.g. cans of pipettes, it is recommended that a liquid indicator is included within the bottle or can. 

Polyethylene naphthalate (PEN) polyesters are made from 2,6-naphthalene dicarboxylic acid or 2,6-naphthalene dicarboxylic acid, dimethyl ester. They have higher temperature resistance than amorphous PET and are increasingly used in applications requiring heat sterilisation of the food/drink, although PEN at the moment is significantly more expensive. Table 10.5 lists commonly used substances in polyesters. 

The organism is sensitive to physical agents such as heat sterilisation, radiation and cold shock [6,7], and it is therefore its resistance to antimicrobial agents which poses the major problem. The continued use of antibacterial agents will no doubt exacerbate the situation unless more effective agents are discovered. 

Kupiec TC, Matthews P, Ahmad R. Dry-heat sterilisation of parenteral oil vehicles. Int J Pharm Compound 2000 4(3) 223-224. 

The drain tap of each tank was also cleaned with hydrogen peroxide (30 g kg" ), leaving the tap filled for at least 2 h. The PTFE tip which was mounted to the drain tap for filling the ampoules was cleaned in the same way. Just before filling the PTFE tip was heat-sterilised. A test was carried out to estimate the losses by evaporation during the preparation of the reference material. The test consisted of filling three ampoules with ultra pure water. After weighing, the ampoules were left at room temperature for a period of 7 days. The relative loss by evaporation was less than 0.02% /day for both types of ampoules (diameter of 40 and 30 mm for respectively CRMs 408 and 409). 

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. 

Centrifuged sewage sludge was obtained from a municipal waste water treatment plant of a large city (100 kg with dry matter content of 21% as mass fraction). The material was heat-sterilised (medium-pressure) at 134°C for three intervals of (1) 75 minutes, (2) 60 minutes and (3) 60 minutes by autoclavation. In between the material was allowed to cool for 60 minutes at ambient temperature. The material was dried in a climate chamber at 20°C under air while being crushed mechanically. This was performed in stainless steel-containers in which the material had been spread and frequently raked for 3 months. Finally the material was dried in a ventilated oven for 48 h at 40°C. 

Like suspensions, ointments can be more difficult to manufacture in sterile form. They can be terminally sterilised alternatively, they must be manufactured from sterile ingredients in an aseptic environment. Filtration through a suitable membrane or dry heat sterilisation is often used. 

For ophthalmic products, there is a dilemma because recent market trends show that flexible LDPE plastic dropper bottles are popular with users because they offer several advantages, including ease of administration, better control of drop delivery and lower risk of contamination during patient use plastic dropper bottles are lightweight, yet more robust than glass. However, one disadvantage of LDPE containers is that they cannot withstand terminal heat sterilisation using pharmacopoeial recommended heat cycles. 

According to the decision trees, where it is not possible to carry out terminal sterilisation by heating due to formulation instability, a decision should be made to utilise an alternative method of terminal sterilisation, filtration and/or aseptic processing. If this alternative route is taken, then a clear scientific justification for not using terminal heat sterilisation will be required in the NDA/MAA dossier. Commercial reasons will not be acceptable because terminal sterilisation offers the highest possible level of sterility assurance. 

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