Sterilization General

In rare instances it is possible to sterilize an article at the time and place of its use. However, sterilization generally takes place at one location prior to use of an article at another location. The main purpose of packaging (qv) is to protect the steriHty of the contents. When an article is placed in its protective container and subsequently sterilized, the process is called terminal sterilization. When it is sterilized first and then placed in a presterilized container, the process is called sterile filling. 

If an effective dry heat depyrogenation is performed, sterilization generally is achieved as well. Effective dry heat sterilization can be performed even without achieving depyrogenation. If moist heat sterilization is performed, in normal operating conditions depyrogenation is not achieved. 

Current pharmacopeias, standards, and guidelines related to sterilization generally use the following type of wording ... 

The number of units sampled for the test varies according to the following factors (1) the number of units per batch, (2) the fill volume of the container, and (3) the method of product sterilization. Generally, 10-20 units are randomly sampled from the lot. If the lot size is between 20 and 200 units, then n = 10. 

The sterile condition, can only exist within barriers that protect it from the non-sterile general environment. An essential prerequisite to the maintenance of sterility is for the product or pait of the product that is required to be sterile to be isolated by cnntahunent within a material impermeable to microbial penetration. If the design of the containment system or primary package does not allow the material of containment to be continuous, all-enveloping, and complete, then the sealing surfaces of the m erial of containment, either to itself or to another material of contaioraeot or to the product itself, must also be impermeable to microbial penetration. The barrier properties of the containment system to... 

An overview of the general principles of filtration having specific appHcation to bacterial and viral removal is given herein. The emphasis is on ensuring that the sterility and/or safety of biologicals and biopharmaceuticals be maintained. 

The General Tests and Assays. This section of the USP gives methods for tests that are general in nature and apply to a number of the substances. Procedures are iacluded for such tests as heavy metals, melting point, chloride, sulfate, sterility, bacterial endotoxins, and pyrogens. Also iacluded are descriptions of various analytical techniques, such as spectrophotometry, chromatography, and nmr, and descriptions of tests to be used on glass or plastic containers, mbber closures, etc. 

Acid foods generally require the simplest equipment for heat preservation. The food can be heated to 100°C and filled hot into suitable containers. The containers are sealed, inverted to sterilize the closure, held at the filling temperature for a short time to ensure that the package is thoroughly heated, and then cooled. Tomato sauces, jellies, fmits, fmit juices (qv), and pickles are routinely preserved in this fashion. 

Solutions for external or oral use do not require sterilization but generally contain antimicrobial preservatives. Ophthalmic solutions and parenteral solutions require sterilization (qv). 

Ophthalmic ointments usually contain petrolatum as the base. The petrolatum is sterilized by dry heat and combined with the sterile dmg powder under aseptic conditions. Ophthalmic suspensions contain very fine (- 10 ji) particle sized soHds suspended in an aqueous vehicle. The vehicle is adjusted to isotonicity and viscosity-increasing excipients, chelating agents, and surfactants also may be needed. The aqueous vehicle in these cases is generally autoclaved and mixed with sterile dmg powder asceptically (30). 

Carboxyhc acid ester, carbamate, organophosphate, and urea hydrolysis are important acid/base-catalyzed reactions. Typically, pesticides that are susceptible to chemical hydrolysis are also susceptible to biological hydrolysis the products of chemical vs biological hydrolysis are generally identical (see eqs. 8, 11, 13, and 14). Consequentiy, the two types of reactions can only be distinguished based on sterile controls or kinetic studies. As a general rule, carboxyhc acid esters, carbamates, and organophosphates are more susceptible to alkaline hydrolysis (24), whereas sulfonylureas are more susceptible to acid hydrolysis (25). 

Hospital and health-care institutions face a different problem. The sterilizer loads are diverse and generally prepared manually. Therefore, the... 

Dry-heat sterilization is generally conducted at 160—170°C for >2 h. Specific exposures are dictated by the bioburden concentration and the temperature tolerance of the products under sterilization. At considerably higher temperatures, the required exposure times are much shorter. The effectiveness of any cycle type must be tested. For dry-heat sterilization, forced-air-type ovens are usually specified for better temperature distribution. Temperature-recording devices are recommended. 

General recommendations for instmmentation include monitoring gas concentration, temperature, time, and the moisture content of the chamber. Hospital sterilizers are not usually equipped with instmmentation providing direct display of gas concentration and moisture content. These rely instead on a specific sequence of steps performed automatically and the recording of pressure which when 100% ethylene oxide is used is a perfect measure for the concentration of this gas. 

Chemical dosimeters based on ferrous sulfate, ferrous cupric sulfate, or ceric sulfate are generally used. Color-change process indicators are also used, but these cannot measure the radiation dose, only the extent of sterilization. 

Composition and Methods of Manufacture. Vaccine is produced from the Oka attenuated strain. Vacciae is produced in human diploid cells such as MRC-5. After growth in the cell substrate, the cells themselves are harvested into the growth medium and sonicated to release the cell-associated vims. Sucrose and buffering salts are generally in the medium to help stabiLize the vims. The vacciae is presented in a free2e-dried vial to be reconstituted with sterile distilled water before injection (27). 

USP XXII general dihydrate 99-107% CaCl2-2 H2O calcium chloride for injections, sterile solution in water, 95—105% of labeled CaCL-2 H,0 ... 

Generally, the fermentation proeess involves the addition of a speeifie eulture of mieroorganisms to a sterilized liquid substrate or broth in a tank (submerged fermentation), addition of air if aerobie, in a well-designed gas-liquid eontaetor. The fermentation proeess is then earried out to grow mieroorganisms and to produee the required ehemieals. Table 11-1 lists examples of the proeesses used by fermentation. 

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]. 

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