Sterilization, terminal

Manufacturing operations for sterile products are divided into two groups, one where the product is sterilized terminally, that is at the end of processing after it has been sealed in its container, and the other where some of the processing must be conducted aseptically. For terminally sterilized products, a grade C environment is usually... 

If the suspension is for parenteral administration, it will need to be sterilized. Terminal heat sterilization can affect both its chemical and physical stability, the latter usually observed as crystal growth or aggregation of the particles (Na et al. 1999). Another measure of suspension stability is the zeta potential, which is a measure of the surface charge. However, various... 

Terg-O-Tometer Terg-o-tometer Terlinguaite [12394-37-5] Termamyl Terminal lakes Terminal sterilization Ternary polymer blends Terne metal... 

In rare instances it is possible to sterilize an article at the time and place of its use. However, steriliza tion 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 stetiHty of the contents. When an article is placed in its protective container and subsequentiy 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. 

Packaging material used for terminal sterilization must permit full stedlant penetration as weU as provide a microbial barrier. Consideration must also be given to the conditions to which the sterile package is to be exposed until used, such as storage, transportation, or frequency of handling. 

The most widely used sterilization method ia the food industry is moist heat. The heat is usually suppHed by high pressure steam, but because most foods already contain moisture the role of steam is to heat the food to the required temperature. The cooking and sterilization processes can frequendy be combined into one. The food may be sealed into impervious containers of glass, metal, or plastic film and undergo terminal sterilization, or it may be presterilized in batches or in a continuous operation and then filled into a presterilized container. The latter process is called sterile filling. 

There are four types of food sterilization processes terminal sterilization in prefiUed containers in a batchwise process terminal sterilization in prefiUed containers of appropriate design heated to the required temperatures in a continuous process aseptic filling foUowing batchwise cooking in an appropriate retort and aseptic filling in a continuous cooking system equipped with appropriate valves to aUow the necessary pressures for attainment of the required sterilization temperatures. 

Clarifying Filters - Usually cartridge-type or bag filters designed to remove small amounts of particles from a solution. Laboratory personnel typically use these types of filters. These types of filters are also used for 0.2 micron terminal sterilization. 

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 above sterilized medium was inoculated with 11 liters of seed inoculum having a bacterial count of approximately 20 billion per cc. The tank was fermented at 37°C without pH adjustment, aeration, or other modification for 14 hours at the end of which time 320 cc of 50% dextrose was added. After this the pH was adjusted to 7.0 at 15 minute intervals with 5.0 N sodium hydroxide. The volume of sodium hydroxide required for neutralization was noted and 115% of this volume of 50% dextrose solution added after each pH adjustment. At the end of about 8 hours the bacterial count had ceased to increase and the fermentation was terminated. At this time the fermentation medium contained approximately 1,000 units of streptokinase per cc. 

Sterilization of the finished drug delivery formulation is an important consideration often overlooked in the early design of lactide/glycolide delivery systems. Aseptic processing and terminal sterilization are the two major routes of affording an acceptably sterile product. Both of these methods are suitable for products based on lactide/glycolide polymers if proper care is exercised in processing or selection of the treatment procedures. 

In cases of severe acute asthmatic attacks, bronchodilators and steroids for direct dehveiy to the lungs may be needed in large doses. This is achieved by direct inhalation via a nebulizer device this converts a liquid into a mist or fine spray. The dmg is diluted in small volumes of Water for Injections BP before loading into the reservoir of the machine. This vehicle must be sterile and preservative-fiee and is therefore prepared as a terminally sterilized unit dose in polyethylene nebules. 

Sterilization methods have been discussed in Chapter 20 and the various types of sterile products have been described in Chapter 21. For manufacturing purposes an important distinction exists between a sterile product which is termirrally sterilized and one which is not. Terminally sterilized means that, after preparation, the produet is transferred to containers which are sealed and then immediately sterilized by heat (or radiation or... 

Aseptically prepared products Terminally sterilized products (TSP) ... 

Sterile filtration, with subsequent aseptic filling, is common because of the heat sensitivity of many drugs. Those drug solutions that can withstand heat should be terminally autoclave sterilized after filling, since this best assures product sterility. 

Large-volume parenterals (LVPs) and small-volume parenterals (SVPs) containing no antimicrobial agent should be terminally sterilized. It is common practice to include an antimicrobial agent in SVPs that cannot be terminally sterilized or are intended for multiple-dose use. The general exceptions are products that pass the USP Antimicrobial Preservative Effectiveness Test [1] because of the antimicrobial activity of the active... 

It has been only in the past 25 years that filters have become sufficiently reliable to use them on a wide scale to sterilize injectable solutions. Even now it is prudent to use filtration to sterilize only those products that cannot be terminally sterilized. 

One can see by the complexity of these types of manufacturing procedures that much care and attention to detail must be maintained by the manufacturer. This sterile manufacturing procedure must then be validated to prove that no more than 3 containers in a lot of 3000 containers (0.1%) are nonsterile. Ultimately, it is the manufacturer s responsibility to ensure the safety and efficacy of the manufacturing process and the absence of any adverse effect on the product, such as the possible formation of substances toxic to the eye, an ever-present possibility with gas sterilization or when using ionizing radiation. For ophthalmic products sterilized by terminal sterilization (sterilization in the final sealed container, e.g., steam under pressure), the sterilization cycle must be validated to ensure sterility at a probability of 106 or greater. 

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