Compounded sterile products

USP Chapter <797> sets forth the following criteria for compounded sterile products ... 

When feasible, compounding procedures are separated from postcompounding quality inspections and review before compounding sterile products is dispensed or administered. 

Risk level classification under USP Chapter <797> is done in general terms except for compounded sterile products prepared from... 

When compounded sterile products are compounded under low-risk conditions and one or more of the following conditions exists, then there is a medium risk of contamination. 

Multiple individual or small doses of sterile products combined or pooled to prepare a compounded sterile product for administration to either multiple patients or to one patient on multiple occasions. 

Sterile compounded products do not contain broad-spectrum bacteriostatic products and the compounded sterile products are administered over several days. 

I. Health care institutions where compounded sterile products are prepared, stored, or dispensed. 

Ben Venue Laboratories founded in 1938, specializes in the manufacturing of sterile products. Its activities and capabilities can be contracted on a project basis. Since its foundation, a long history of experiences on customized production of a wide variety of sterile products. Product portfolio includes lyophilized dosages, liquid dosages, small molecule compounds, biologicals, cytotoxics, diagnostics, veterinary products, potent compounds. 

Subpart C, Drug Compounding Faeilities. These are discussed further in the next seetion of this article. It also discusses bulk drugs and materials as well as the compounding of sterile products, radiopharmaceuticals, and products requiring special precaution such as the handling of penicillins. 

Appropriate procedures, designed to prevent microbiological contamination of compounded drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of any sterilization process. 

The equipment needed is determined by the type and extent of the services chosen to provide. Hospitals already utilize laminar flow hoods for aseptic compounding of sterile solutions. The same hoods can be used to compound other sterile products such as eye drops. A balance, preferably electronic, is essential. Ointment slabs (pill tiles), along with spatulas of different types and materials, should be on hand. A few mortars and pestles (both of glass, ceramic, and/or plastic) should be obtained and some glassware. It may not be necessary to buy a roomful of equipment, but one should purchase what is needed to start the service, and build it up as the service grows and expands to different arenas. 

It is necessary to adjust the Ca, Mg, phosphate, and citrate content of the concentrate to control aggregation and precipitation of the proteins and minerals during sterilization. By controlling protein aggregation, this adjustment provides optimum viscosity to stabilize the protein, mineral, and milk fat emulsion systems during prolonged storage of the sterile product. Some milk concentrates are stabilized by addition of Ca and Mg salts, whereas others are stabilized by addition of phosphate or citrate salts (Parry, 1974). Chemical compounds approved for addition to evaporated milk include calcium chloride, sodium citrate, and disodium phosphate (CFR 1982). 

Capabilities—solid dosage, sterile products, liquids/semisolids, potent compound, different licensure (DEA, etc.)... 

Aseptic compounding is often a required activity for sterile products that cannot be filter sterilized. The preparation of the sterile solids for use in these formulations is outside the scope of this chapter, but it is often acknowledged as the most difficult of all pharmaceutical processes to properly execute. Handling these materials at the fill site is performed using ISO 5 environments, and the use of closed systems is preferred [34],... 

The USP recognizes six methods of achieving a sterile product (i) steam sterilization, (if) dry-heat sterilization, (Hi) gas sterilization, (iv) sterihzation by ionizing radiation, (v) sterilization by filtration, and (vi) aseptic processing (67). For ophthalmic products packaged in plastic containers, t5rpical for ophthalmic products, a combination of two or more of these six methods is routinely used. For example, for a sterile ophthalmic suspension, bottles, dropper tips, and caps may be sterilized by ethylene oxide or y-radiation the suspended solid may be sterilized by dry heat, y-radiation, or ethylene oxide and the aqueous portion of the composition may be sterilized by filtration. The compounding is completed under aseptic conditions. 

The effect of the autoclave cycle, i.e., fill, heat-up, peak dwell and cool down, on the theoretical chemical stability of compounds intended for IV injection has been investigated by Parasrampuria et al. (1993). Assuming first-order degradation kinetics, i.e., hydrolysis, the amount of degradation was calculated for any point during the above process. Although the results were calculated for first-order kinetics, the authors estimated that the calculations were applicable to other reaction orders, i.e., zero and second. Acceptable reasons for not proceeding with a terminally sterilized product are as follows ... 

For sterile Filtration of ophthalmics and small-volume parenteral products it is not unusual to Find several Filters mounted in series. For instance a compounded bulk product may be Filtered through the wall from a dean area into an aseptic filling room. In these cases there are usually two filters mounted in... 

The pharmacopoeias deal with ingredient water of two types. Purified Water and Water for Injection. The principal difference in biological quality between the two types of water is that Water for Injection is specified to be pyrogen-free (less than 0.25 Eu of bacterial endotoxin per mL). Only water of Water for Injection quality may be used to dissolve, dilute, or compound parenteral products, because endotoxins may pass through 0.22 pm sterilizing filters. Control of bacterial endotoxins is achieved in the first instance through control of microbiological contamination. 

ASEPTIC PROCESS (procede aseptique) A method of produdng a sterile product in which sterile bulk drug or sterile raw materials are compounded and assembled with sterile packaging components under Grade A or conditions. 

Sterilization is a term referring to any process that eliminates or kills all forms of microbial life, including transmissible agents such as fungi, bacteria, viruses, spore, etc., which are present on a surface or contained in a fluid or a compound such as a medical textile material. Sterilization can be achieved by applying heat, chemicals, irradiation, high pressure, or filtration. In the medical textile industry, the main methods used to sterilize products are heat, ethylene oxide, gamma irradiation, and electron radiation. 

Pharmaceutical Industry. In the pharmaceutical industry, sterility of deionized water systems is maintained by using an ozone residual. The ozone residual concentration is maintained at >0.3 ppm ppm in the water recirculation loop. Prior to product compounding, the ozone residual is removed by contact with uvirradiaton for <1 s. Ozone also is used to oxidize pyrogens from distilled water destined for intravenous solutions. 

The production test showed that the epoxy phenolic enamel was the preferred enamel for coating tinplate containers used in packaging irradiation-sterilized ham and beef. The preferred end-sealing compound for the same application was the blend of cured and uncured isobutylene-isoprene copolymer. 

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