Injections microbial contamination

Advantages of the intramuscular and subcutaneous routes include an increased reliability and precision in the drug blood level Anally achieved and reasonably rapid absorption and onset of drug action. There are, however, serious disadvantages as well. Pain, tenderness, local tissue necrosis (primarily with highly alkaline injections), microbial contamination, and nerve damage may be associated with these forms of parenteral administration. 

Several guidelines are available in the literature for the pharmacist who must extemporaneously prepare an ophthalmic solution. The USP contains a section on ophthalmic solutions, as do other compendia and several standard textbooks. Since the pharmacist does not have the facilities to test the product, he or she should dispense only small quantities, with an expiration date of no more than 30 days. Refrigeration of the product should also be required as a precautionary measure. To reduce the largest potential source of microbial contamination, only sterile purified water should be used in compounding ophthalmic solutions. Sterile water for injection, USP, from unopened IV bottles or vials is the highest-quality water available to the pharmacist. Prepackaged sterile water with bacteriostatic agents should not be used. 

As with traditional aseptic filling, in order to comply with pharmaceutical GMP, it is important to minimize contamination at all stages of manufacture. Raw materials should be of a high quality and tested for microbial contamination. Water used for product manufacture should be of low bioburden and high purity (preferably water-for-injection quality, although this requirement is dependent upon the nature of the product being manufactured). 

Antimicrobial preservatives are added to multiuse nonsterile liquids, ointments, and ereams, and sterile injectable products to protect them from microbial contamination that may be introduced inadvertently during use of the product (postmanufacturing). 

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). 

Injectable drug products require protection from microbial contamination (loss of sterility or added bioburden) and may also need to be protected from light or exposure to gases (e.g., oxygen). 

Preservatives. These are included in pharmaceutical preparations to prevent microbial spoilage of the product and to minimize the risk of the consumer acquiring an infection when the preparation is administered. Preservatives must be able to limit proliferation of microorganisms that may be introduced unavoidably into non-sterile products such as oral and topical medications during their manufacture and use. In sterile products such as eye-drops and multi-dose injections preservatives should kill any microbial contaminants introduced inadvertently during use. It is essential that a preservative is not toxic in relation to the intended route of administration of the preserved preparation. 

The solutions used for the dissolution of injectable products are prepared by using Water for Injection (WFI) USP that has been made as described in Ch. 13 of this handbook. In some cases, solutions are prepared using organic solvents (e.g., acetone, methanol, ethanol, isopropanol) alone or in combination with WFI. The potential for preventing microbial contamination should dominate the delivery and storage systems for water and solvents. 

If there are significant amounts of both volatile and nonvolatile contaminants, remediation may be achieved by a combination of Hquid and vapor extraction of the former, and bioremediation of the latter. This combination has been termed "bioslurping", where the act of pumping out the Hquid contaminant phase draws in air at other wells to stimulate aerobic degradation (20). Such bioremediation requites that there be enough nutrients to allow microbial growth, and fertilizer nutrients are frequendy added at the air injection wells. Bioslurping has had a number of weU-documented successes. 

Significant and active microbial populations are usually found in the subsurface soil and ground-water. However, if there is a lack of required microorganisms, then bacteria can be injected in situ. An optimum food/microorganisms (F/M) ratio should be maintained for effective removal of organic contaminants. 

Bioventing technology was developed by the U.S. EPA Risk Reduction Engineering Laboratory to treat soil contaminated by numerous industrial wastes, which is subjected to aerobic microbial degradation, especially to promote the degradation of polycyclic aromatic hydrocarbons.65 It uses a series of air injection probes, each of which is attached to a low-pressure air pump. The air pump operates at extremely low pressures to allow the inflow of oxygen without volatilization of contaminants. Additional additives such as ozone or nutrients may also be supplied to stimulate microbial growth.77... 

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