Sterile precautions

The fermenters are inoculated with 7.5% by volume of a 24-hour old culture of Aspergillus sderotiorum Huber grown at 28°C in 50 ml aliquots of the above described soybean-glucose medium contained in 300 ml Erlenmeyer flasks, placed on a shaker rotating at approximately 230 rpm. The inoculated fermenters are agitated at 1,380 rpm and each aerated with 1 liter of air per minute and at a temperature of 28°C for 47 hours. A silicone antifoam is added when required. At the end of the 47-hour period, the pH of the fermentation broth rose to 6.8 to 6.9. Sulfuric acid is then added with sterile precautions to restore the pH to 6.5. 

Severe dyspnea develops or X-ray or blood gases consistent with Sterile precautions PRN... 

After the high temperature phase of a heat sterilization cycle, precautions should be taken against contamination of a sterilized load during cooling. Unless it can be shown that the product cannot be contaminated by it, and cooling fluid should be sterile. Precautions should be taken to prevent contamination by non-stenle air entering the autoclave or oven as it cools. 

A single indwelling arterial or venous line may be used for feeding and monitoring purposes provided that supplemental feeding techniques are used. If total intravenous nutrition is undertaken, the sterility precautions require that a second separate access line be placed for monitoring purposes. 

Safe condition at the time of delivery by the seller will, however, include proper packaging, necessary sterilization, and other precautions required to permit the product to remain safe for a normal length of time... 

If products are to be of a sterile nature or their requirements are such that these should be free of objectionable microorganisms, precautions must be taken to aid in this final goal... 

Frequent checks should also be made on the sterility of S9 preparations, media and test articles. These simple precautions can prevent loss of valuable time and resources. 

Contamination with endotoxin is an important and frustrating problem in LEH manufacturing for two reasons. Firstly, hemoglobin has a strong tendency to bind endotoxin, where one hemoglobin molecule binds to four endotoxin molecules (K 3.1 x lO M) (117). Secondly, endotoxin has amphiphilicity that enables its stable insertion into lipid bilayer. Such an interaction not only presents contamination and stability problems, but also hampers accurate quantitation of endotoxin. The best possible way to prevent endotoxin contamination is to use aseptic precautions with utmost care. All the machinery, filters, and water should be endotoxin-free. Glass and metallic components may be dry-heat sterilized at about 200° C for three... 

Subpart C, Drug Compounding Faeilities. These are discussed further in the next seetion of this article. It also discusses bulk drugs and materials as well as the compounding of sterile products, radiopharmaceuticals, and products requiring special precaution such as the handling of penicillins. 

Another group of blood tests involves bacteriological techniques. Blood and bone marrow samples are obtained under aseptic precautions and introduced into a variety of artificial culture media, with subsequent isolation and identification of the specific microorganism responsible for the illness. Relative susceptibility of the specific strain of bacteria to the available chemotherapeutic and antibiotic agents may then be determined and the effectiveness of such agents in sterilizing the blood-stream can be determined by further blood cultures. 

Another SOP category related to the physical facility is environmental control. All plants must be kept free of rodents and insects. Such an SOP will indicate acceptable materials to be used, precautions to prevent product and personnel contamination, frequency, and area-monitoring procedure. In some operations, such as an area to manufacture sterile products, there are requirements for control of air temperature, humidity, flow rates and patterns, and particulate matter. These SOPs require steps such as checks to be performed, including temperature reading and frequency, maintenance to be performed, such as changing air filters and frequency, recording instrument checks, and calibration, such as for temperature and frequency. A prototype SOP is illustrated in Figure 6. 

Sterilizers and SIP systems in the facility are supplied with steam which upon condensation meets WFI quality requirements (testing steam condensate for microbial content is not fruitful). The steam can be produced directly from the water of sufficient purity to meet the input requirements of the steam generator. Steam generators are phase transition technologies that operate like a still, so it is no more necessary to provide these devices with WFI feed water than it would be to double distill WFI. (Production from WFI is certainly possible, but that is both expensive and an unnecessary precaution.) Modest quantities of steam can be produced from the first effect of a multiple effect WFI still, however, with a resultant loss of WFI output [18]. 

Tablets, hypodermic Molded tablet triturates intended to be dissolved in water to make a solution to be injected parenterally. The usual weight of hypodermic tablets is about 0.03 g, which distinguishes them from ordinary tablet triturates that weigh about 0.06 g. Formerly prepared extemporaneously by pharmacists, modern compressed hypodermic tablets are not intended to be sterile, although they are manufactured under strict conditions as a precaution against contamination (see Triturates, tablet) ...

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