Sterility standards

Disinfection/sterilization Chemieal disinfeetants are a more praetieal means of inaetivating infeetious agents when eompared to sterilization. Standard sterilization teehniques are generally impraetieal for large equipment and for nondisposable PPE. For this reason, disposable PPE is reeommended for use with infeetious agents [1]. 

Downstream processing involves employment of a purifying system that can isolate the product in as few steps as possible using the simplest purification technology that will achieve the required purity. While purity is a critical consideration for both small-molecule pharmaceuticals and biopharmaceuticals, the nature of biopharmaceutical administration (typically via injection) and the nature of biotechnology processes require that additional considerations be paid to the purity of biopharmaceuticals. The final product must meet regulatory purity and sterility standards and must be below the maximally acceptable cellular or microbial contamination (Ho and Gibaldi, 2003). 

Parenteral dosage forms require extensive testing of sterility and biological impurity contamination because of the high sensitivity of this administration route. These same sterility standards do not apply to solid and... 

Table 6 Effect of roughness and sterilization standard deviation) of PLA/G5 on the composite wettability (mean values ...

Miller A, Hansen J. Revision of the ISO and EN radiation sterilization standards. Radiat Phys Chem 2002 63 665-7. 

Some scientific studies indicate that the gam in performance obtained through the use of anabolic steroids is small This may be a case though in which the anecdotal evidence of the athletes may be closer to the mark than the scientific studies The scientific studies are done under ethical conditions in which patients are treated with prescription level doses of steroids A 240 pound offensive tackle ( too small by todays standards) may take several ana bolic steroids at a time at 10-20 times their pre scribed doses in order to weigh the 280 pounds he (or his coach) feels is necessary The price athletes pay for gams in size and strength can be enormous This price includes emotional costs (friendships lost because of heightened aggressiveness) sterility testicular atro phy (the testes cease to function once the body starts to obtain a sufficient supply of testosterone like steroids from outside) and increased risk of prema ture death from liver cancer or heart disease... 

The earliest commercially available filters were manufactured in two pore sizes 0.45 and 0.8 pm. The 0.45 pm-rated membranes were considered to be stefilizing-grade filters and were successfully used in the sterile filtration of pharmaceuticals and parenterals. The membrane filters were qualified using Serratia marcescens a standard bacterium, having dimensions of 0.6 x 1 pm. However, in the late 1960s it became apparent that the matrix of the 0.45 pm-rated filters could be penetrated by some pseudomonad-like organisms (1). For sterile filtration apphcations in the 1990s, 0.2 pm-rated membranes are the industry standard in the manufacture of sterile parenterals and pharmaceuticals. 

Filters for use in sterile gas filtration must conform to standards similar to those mandated for sterile hquid filtration. Nondestmctive integrity tests may be apphed. The tests are performed by wetting the filter with an appropriate solvent, commonly 60/40 isopropyl alcohol/water for hydrophobic membranes, and applying air or nitrogen gas at a preset pressure. 

Milk has been a source for food for humans since the beginning of recorded history. Although the use of fresh milk has increased with economic development, the majority of consumption occurs after milk has been heated, processed, or made into butter. The milk industry became a commercial enterprise when methods for preservation of fluid milk were introduced. The successful evolution of the dairy industry from small to large units of production, ie, the farm to the dairy plant, depended on sanitation of animals, products, and equipment cooling faciUties health standards for animals and workers transportation systems constmction materials for process machinery and product containers pasteurization and sterilization methods containers for distribution and refrigeration for products in stores and homes. 

The processing operations for fluid or manufactured milk products include cooling, centrifugal sediment removal and cream (a mixture of fat and milk semm) separation, standardization, homogenization, pasteurization or sterilization, and packaging, handling, and storing. 

Hospital sterilizer loads vary in composition, thus the challenge presented to the test organism can vary considerably, depending on the type and contents of packages in which they are placed. The benefits of a standardized test-pack constmction and test protocol are obvious, and such recommendation is made by AAMI for steam and ethylene oxide sterilizers (11). More recentiy in European (CEN) and International (ISO) standards, biological indicators are considered as additional information supplemental to the measurement of physical parameters. Indeed, for sterilization using moist heat (steam), the biological indicator information is not considered to be relevant. 

The effect of various pHs has been well known for some time. Acidic foods such as fmits tend to retard microbial growth and resist certain types of contamination. For this reason, the standards adopted industry-wide have been based on the processing of foods of high acidity (low pH). In the United States, the FDA has regulatory responsibiUty over the preparation, sterilization, and distribution of foods. 

Another standard test, which is much simpler and more convenient, is the membrane filter technique. A suitable volume of sample is filtered through a sterile, 0.45-p.m membrane filter. The filter is placed in a petri dish containing a specific growth medium (M-Endo nutrient broth, M-Endo medium) and incubated for 24 h at 35°C. If after this time the colonies show the characteristic green sheen, this is taken as positive evidence for the presence of the coliform group (see Water, sewage). 

The first two categories, clarifying and crossflow filters, have been very well developed and optimized for use in biotechnology and standard wastewater treatment applications. Equipment is easily available for these applications, whether as small 0.2 micron sterilizing filter used to terminally sterilize 100 ml of product solution, or a small 500 ml crossflow filter used to concentrate a small amount of antibody solution. Many vendors of this equipment to wastewater treatment applications have their origins in the CPI (Chemical Process Industries), and have incorporated many of the scale-up and optimization properties developed in much larger units used in large scale chemical production. As a result, these two filtration unit operations are one of the most optimized and efficient used in wastewater treatment. 

The purpose of open unidirectional airflow benches is to protect products from particulate contaminants by creating a controlled environment. These benches are used, for example, in electronic, biological, pharmaceutical, and food industries. It should be mentioned that within pharmaceutical production, aseptic sterile processes must be carried out in a Class 100 environment (U.S. Federal Standard 209 E, Airborne Particulate Cleanliness Classes in Cleanrooms and Clean Zones). To avoid particle contamination in the bench, horizontal or vertical airflow with high-efficiency particulate air (HEPA)-filtered air is used. The air velocity is normally 0.4-0.5 ra s". Some examples of typical arrangements of open unidirectional airflow benches are shown in Fig. 10.51. 

Machine operators working with emulsions can become susceptible to skin infections because of the combination of the de-fatting effect of soluble-oil emulsifiers and the abrasive action of metallic scarf, but bacteria in cutting fluids are seldom the source of such infections. High standards of personal hygiene and the use of barrier creams should prevent such problems. A more difficult situation arises when a soluble-oil emulsion becomes infected with bacteria capable of utilizing the emulsifier and mineral-oil components in the system. Even in clean conditions, untreated soluble-oil emulsions and solutions cannot remain completely sterile for any length of time. 

Therrtial Sterilization of Pouches of Beef. Methodology for food thermoprocessing in cylindrical metal containers assured food sterility in flexible packages. Beef slices (1.25 cm thick) were steam cooked to an internal temperature of 72°C and vacuum sealed in pouches to give a fill of 120 g. These pouches of beef were processed in a standard retort with complete water circulation and a superimposed air pressure of 1.7 X 105 Pa. The retort schedule—a 40-minute cook at 118°C plus come-up time followed by a 30-minute cooling time—achieved a F0 (lethality value) of 6. 

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