Sterilization requirements

Bacteriological sampling is performed by manual techniques because of stringent sterilization requirements. Samples are taken in wide-mouthed, sterile, glass-stoppered bottles that are wrapped in paper prior to sterilization in an autoclave at 138 kPa (20 psi) or in an oven at 170°C. The botde is unwrapped and the lower portion is held in the hand. The sample is taken with the botde mouth in the direction of the flow. The stopper must be protected from contamination, the botde only partially filled, and the sample stored at 4°C after sampling. For bacteriological samples withdrawn from a tap, the water should mn for five minutes and then be shut off the tap should then be sterilized by flaming before a sample is taken. 

The sterilization processes described in the Ph Eur are preferred, especially terminal sterilization in the final container alternative processes have to be justified. All sterilization processes will need to be described and appropriate in-process controls and limits included. Where Ph Eur prescriptions are followed, there should be a statement to this effect in the application. Most of this information should be discussed in the development pharmaceutics section. Reference is made to the specific guidelines on ethylene oxide sterilization and irradiation sterilization, which are discussed further below. The possibility of parametric release for terminal processes such as saturated steam and irradiation is mentioned (see below). For all sterile products there should be a sterility requirement included in the finished product specification regardless of the outcome of validation studies. 

Even where it is possible to omit routine or even any sterility testing of finished product, the sterility requirement should be retained in the finished product specification. 

In summary, water can be a source of contaminants. If the raw material (drinking water) complies with the quahty parameters established by authorities, contaminants still present can be eliminated by usual water purification processes available to the pharmaceutical industry. While distillation and reverse osmosis provide water with the quality specifications for purified water and highly purified water, WFI is generally obtained by membrane filtration (associated with another purification process) not only because of chemical contamination but mainly because of sterility requirements. 

Among the techniques discussed, moist heat is the most economical and efficient for the general sterilization requirements of fermentation. Therefore, the following four sections describe cell death kinetics and sterilization operations utilizing moist heat. 

The sterilization of freeze-dryers by steam is described in [34] including a guideline for its validation. Steam sterilization is the most applied method today, because ethyleneoxide and formaldehyde have to be used with great care and residues are difficult to measure and to remove. Steam sterilization requires a vac-... 

Other components, is rendered sterile separately, asep-tically weighed, and incorporated in preparing a final product that meets the sterility requirement. This is done because of difficulty in terminal product sterilization, such as lack of penetration of steam into the ointment base and instability of components owing to high dry heating. Antimicrobial preservatives such as methylparaben (0.05%) and propylparaben (0.01%) and its combinations phenylmercuric acetate (0.0008%), chlorobutanol (0.5%),and benzalkonium chloride (0.008%) are used as needed. 

If the damaged strand is carried over into a new reaction vessel, it is prevented from functioning as a template for amplification. Effective sterilization requires the use of these reagents at concentrations that are tailored to the length and sequence of the target and the level of amplification (Table 3). 

A drug administered parenterally is one that is injected through the hollow of a fine needle into the body at various sites and to various depths. The three primary routes are subcutaneous (SC, SubQ), intramuscular (IM), and intravenous (IV). Strict sterility requirements make this dosage form more expensive and require competent trained personnel for administrations. 

Sterilization requires appropriate conditions of humidity, gas concentration, temperature and time. 

Correct sterilization requires that the materials and products are completely subjected to the conditions of the respective process. For this purpose, the process used must be validated with consideration of the type of lot. This validation must be repeated by a specified schedule and must also be performed whenever significant equipment modifications are made. 

Inert gas, usually nitrogen, circulating in the cycle is continuously supplied with a fresh makeup gas. For a spray dryer with evaporation rate of acetone, 110 kg/h, approximately 3 m /h makeup nitrogen is necessary during normal operation. Purging of the installation after washing and sterilization requires approximately 75 m nitrogen. 

A complete chromosome analysis of male sterility requires the examination of each of the four autosomes in all three possible combinations (m/m, a/m, a/a) and under all possible backgrounds for the other chromosomes. This clearly demands an inordinate amount of effort. As an alternative, we have examined a number of cases in which the two sex chromosomes occurred in different combinations and appeared, from the outset, to be of special interest (Zouros et al., 1988 Zouros, 1989). Males of the type Xm/Ym are mostly fertile (more acQurately, they have motile sperm sperm motility is the phenotype that we score in these experiments), except when they carry an arizonae third chromosome (i.e. when they are Xm/Ymllla/m), in which case many have immotile sperm. Males of the type Xa/Ya can be fertile or sterile depending on whether... 

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