Aseptic compounding

Aqueous products moist heat at 121°C/15 minutes then moist heat to achieve a F0 value of not less than 8 minutes to achieve a sterility assurance level of 10 6 then aseptic filtration and aseptic processing then the use of presterilized components and aseptic compounding and assembly... 

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. 

Where products are filled using in-line filtration direct to the filling machine, an aseptic compounding area may not be present. In those instances the final sterilizing filter will be located in the fill room. 

Products that are held/processed in sterilized vessels prior to filling require an aseptic compounding area. This is typically an ISO 7 in environment with localized... 

Depending upon the formulations being produced, additional sterilized processing equipment may be present in this area for use in the process. This can include in-line homogenizers, static mixers, and colloid mills. Where sterile powders are produced, the aseptic compounding processes can include blending, milling, and subdivision equipment. 

Aseptic compounding areas typically require a means to introduce sterile equipment, tubing, and other items, so access to a sterilizer is desirable. The aseptic compounding area may be contiguous to the aseptic filling suites. If it is not, separate gowning areas must be provided for personnel as well as separate air locks/pass-throughs (see below). 

Personnel working in aseptic compounding wear full aseptic garb sterile gown, hood, face mask, goggles, foot covers, and gloves. Adaptations may be necessary for potent/toxic compounds to assure operators are properly protected from hazardous materials. 

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],... 

Use pre-sterilised individual components and aseptic compounding and filling. 

Compounding process involves complex aseptic compounding. 

Into each of 27 Erlenmeyer flasks are placed 150 mg of Kendall s Compound E (cortisone). The flasks and contents are then sterilized for 15 minutes at 15 pounds steam pressure (120°C). To each flask are then added 5.0 ml of ethanol. The 24-hour bacterial culture is then transferred aseptically and the resulting suspensions are shaken on a shake table at 220 rpm and 2B°C for 4B hours. The final pH is 7.2. 

When an ophthalmic ointment is manufactured, all raw material components must be rendered sterile before compounding unless the ointment contains an aqueous fraction that can be sterilized by heat, filtration, or ionizing radiation. The ointment base is sterilized by heat and appropriately filtered while molten to remove extraneous foreign particulate matter. It is then placed into a sterile steam-jacketed kettle to maintain the ointment in a molten state under aseptic conditions, and the previously sterilized active ingredients) and excipients are added aseptically. While still molten, the entire ointment may be passed through a previously sterilized colloid mill for adequate dispersion of the insoluble components. 

Several limitations on the synthetic techniques that can be employed are imposed by the need for rapidity and minimization of handling because of the radiation hazard, and the low concentration and small physical quantities of the compounds. Purification steps should be eliminated if possible by optimizing yields. Where purification is unavoidable, simple procedures are employed such as use of anion exchange columns to remove perrhenate (the most common contaminant in the final product). A variety of disposable sample preparation columns are well suited to this purpose and are available containing small quantities of anion or cation exchange materials (0.1 to 0.5 g typically) such as quaternary ammonium-, primary ammonium-, or sulfonate-derivatized silica. Reversed phase columns are also often used (C8 or C18-derivatized silica). The purification is often thus reduced to a simple filtration step which can be performed aseptically. 

The effect of mineral and organic soil constituents on the mineralisation of LAS, AE, stearyl trimethylammonium chloride (STAC) and sodium stearate (main soap component) in soils was studied by Knaebel and co-workers [38]. The four 14C-labelled compounds were aseptically adsorbed to montmorillonite, kaolinite, illite, sand and humic acids and subsequently mixed with soil yielding surfactant concentrations of about 50 jig kg-1. The CO2 formation in the serum bottle respirometers was monitored over a period of 2 months indicating that the mineralisation extent was highest for LAS (49-75%). Somewhat lower amounts of produced CO2 were reported for AE and the stearate ranging from 34-58% and 29-47%, respectively. The mineralisation extent of the cationic surfactant did not exceed 21% (kaolinite) and achieved only 7% in the montmorillonite-modified soil. Associating the mineral type with the mineralisation kinetics showed that sand... 

Tor European aseptically produced products with sterile raw materials, where sterile filteration is not carried out, then dispensing and compounding shall be in a grade A area, with a grade B background. 

Sterile radiopharmaceuticals may be divided into those which are manufactured aseptically and those which are terminally sterilized. In general, it is advisable to use a terminal sterilization whenever this is possible. Terminal sterilization is defined as a process that subjects the combined product/container/closure system to a sterilization process that results in a specified assurance of sterility [7], Since sterilization of solutions normally means autoclaving (steam sterilization), one must assure that the radiopharmaceutical product does not decompose when it is heated to temperatures above 120°C. Many radiolabeled compounds are susceptible to decomposition at higher temperatures. Proteins, such as albumin, are good examples of this. Others, such as 18F-fluodeoxyglucose (FDG), can be autoclaved in some formulation but not in others. 

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