Aseptic filtration

The anhydrous petrolatum base may be made more miscible with water through the use of an anhydrous liquid lanolin derivative. Drugs can be incorporated into such a base in aqueous solution if desired. Poly-oxyl 40 stearate and polyethylene glycol 300 are used in an anti-infective ointment to solubilize the active principle in the base so that the ointment can be sterilized by aseptic filtration. The cosmetic-type bases, such as the oil-in-water (o/w) emulsion bases popular in dermatology, should not be used in the eye, nor should liquid emulsions, owing to the ocular irritation produced by the soaps and surfactants used to form the emulsion. 

Aqueous products moist heat at 121°C/15 minutes then moist heat to achieve a F0 value of not less than 8 minutes to achieve a sterility assurance level of 10 6 then aseptic filtration and aseptic processing then the use of presterilized components and aseptic compounding and assembly... 

Allergenic extracts are sterile concentrates (solutions or suspensions) of the substances (allergens) responsible for unusual sensitivities in humans. These products can be used for therapeutic or diagnostic purposes. Extracts are aqueous (0.9% sodium chloride used as the diluent) or glycerinated (50%i glycerin as the diluent). Most preparations are buffered at pH 8 and contain phenol (<0.4%) as an antimicrobial preservative. They are sterilized by aseptic filtration. 

Peanut oil is an essentially stable material. However on exposure to air it can slowly thicken and may become rancid. Solidified peanut oil should be completely melted and mixed before use. Peanut oil may be sterilized by aseptic filtration or... 

Sesame oil may be sterilized by aseptic filtration or dry heat. It has been reported that suitable conditions for the sterilization of injections containing sesame oil are a temperature of 170°C for 2 hours it has been suggested that 150°C for 1 hour is inadequate. However, it has been demonstrated that dry heat sterilization of sesame oil at 150°C for 1 hour was sufficient to kill all added Bacillus subtilis spores. ... 

Another option is the aseptic processing, which involves a series of aseptic steps. Each of them must be highly controlled since the introduction of micro-organisms must be avoided all along the process. Aseptic filtration or aseptic processes are time-consuming, expensive, difficult to monitor and the SAL value is limited to 10 -10 , so alternative methods for sterilization of thermosensitive solid drugs are needed. 

For parenteral IV formulations, a sterile solution of the compound is required. A terminal sterilization method is preferred, rather than aseptic filtration, because there is a greater assurance of achieving sterility. As noted by Moldenhauer (1998), the FDA requires a written justification to explain why a product is not terminally sterilized. Therefore, it is mandatory to assess whether the candidate drug is stable to autoclaving as part of any preformulation selection process. Autoclaving (usually 15 min at 121°C) at various pHs is undertaken, after which the solutions should be evaluated for impurities, colour, pH and degradation products. Clearly, if one compound shows superior stability after autoclaving, then this will be the one to choose. 

It was demonstrated that the drug in the formulation could not withstand terminal heat sterilisation. Furthermore, the product was poured into LDPE bottles fitted with an LDPE dropper plug and polypropylene cap, which could not withstand heat sterilisation either. It was therefore necessary to develop a process to sterilise the solution by aseptic filtration followed by aseptic filling into pre-sterilised packaging components. This process was accomplished by exposure of the drug, the LDPE bottles, the dropper plug and the polypropylene cap to ethylene oxide. 

Process development studies showed that terminal sterilisation of the gel was not possible. Heat sterilisation and gamma irradiation methods both caused unacceptable physical degradation of the gel and also caused chlorbutol hydrolysis. Aseptic filtration was not possible because the drug was suspended in the gel vehicle and viscosity would also have been a problem. The process described below was therefore developed with consideration of the sterilisation of the product components and the maintenance of asepsis throughout manufacture. 

Certain products that cannot be terminally sterilised may be subjected to an aseptic filtration procedure [11] using a satisfactory sterile membrane filter membrane, tightly fixed in a filter holder. The operator passes the liquid product through a sterile and bacteria retentive membrane, mostly with a nominal pore size of 0.2 pm or smaller. Such membrane filters can capture most bacteria, yeasts and fungi, but not all viruses and mycoplasms. The liquid should be asepti-cally collected in a sterilised dedicated clean container directly after sterile filtration. 

As shown in Table 30.1, non-spore forming bacteria do not survive 30 min at 100 °C, and neither do yeasts, fungi, and viruses. Combination of this process with sterilising membrane filtration and aseptic circumstances, gives a higher degree of certainty than aseptic filtration alone as is applied in preparation of eye drops, see Sect. 10.7, notably Tables 10.18 and 10.19. 

This chapter does not cover the situation where medicines that caimot be sterilised in their final container are sterilised by aseptic filtration. 

Medicines, which caimot be sterilised in their final container, are sterilised by aseptic filtration. The standards required for aseptic processing are laid down in Annex 1 of EU GMP [1]. Aseptic processing is called aseptic preparation in Annex 1 (see Sect. 31.1). 

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