Sterile bulk materials

A suitably sized solution preparation system similar to that mentioned under the previous sections can be used to provide material for bulk freeze drying. (Since product solutions can be sterile-filtered directly into the final container, microbial and particulate exposure will be minimized.) The sterile solution is subdivided into trays and placed into a sterilized freeze dryer. Aseptic transfer of sterile product in trays to the freeze dryer must be validated. After tray drying, the sterile product is aseptically transferred through a mill into suitably designed sterile containers. The preparation of sterile bulk material is usually reserved for those cases where the product cannot be isolated by more common and relatively less expensive crystallization methods. Due to recent advances in this field, a freeze drying process should be considered as a viable option. ... 

FILLING VIALS WITH STERILE BULK MATERIALS... 

Isolation technology— The use of isolators and closed systems for the production of sterile bulks is strongly recommended. As with any aseptic process, the sterility assurance level associated with a sterile bulk material is closely related to the extent of direct human intervention with the material. Isolators and closed systems minimize the need for personnel... 

Especially if sterile preparations are made from nonsterile bulk materials, pyrogen testing should be done at the pharmacy or in a contract laboratory. 

Addition to an aseptic processing line of new equipment made of different materials (e.g., stainless steel versus glass, changes between plastics) that will come in contact with sterilized bulk solution or sterile drug components, or deletion of equipment from an aseptic processing line. 

Ethylene oxide (bp, 10.8°C) is a gaseous alkylating agent. It alkylates proteins and ribonucleic and deoxyribonucleic acid in micro-organisms. It replaces labile hydrogen with hydroxyethyl groups. Ethylene oxide is utilized as a surface sterilant. Bulk crystalline materials can occlude vegetative bacterial cells or spores with crystals. Consequently, ethylene oxide does not reach them. The final step prior to sterilization is an aseptic recrystallization step. 

The three human IgG products discussed here were purified from Fraction II -I- III paste by slightly different processing methods but all three shared the same final formulation in 0.2 M glycine, pH 4.25. All three were 10% protein solutions, of which 98% was IgG, and their monomer contents were greater than 90%. At production scale, IgG final bulks (pH 4.25) are typically sterile filtered, aseptically filled into sterile final containers and incubated at 20-27°C for 21days-28days. For the virus studies, however, IgG final bulk material was spiked with virus and adjusted to pH 4.3 or 4.5 before incubating at 5, 20, or 23°C, for up to 28 days. Hanks Balance Salt Solution (HBSS) or IgG, adjusted to pH 7, were also spiked with virus and included as positive controls. Aliquots for virus... 

Chlorocresol is stable at room temperature but is volatile in steam. Aqueous solutions may be sterilized by autoclaving. On exposure to air and light, aqueous solutions may become yellow colored. Solutions in oil or glycerin may be sterilized by heating at 160°C for 1 hour. The bulk material should be stored in a well-closed container, protected from light, in a cool, dry place. 

Aqueous phenoxyethanol solutions are stable and may be sterilized by autoclaving. The bulk material is also stable and should be stored in a well-closed container in a cool, dry place. 

Due to the nature of the final formulation and its end use, the prednisolone Z-butylacetate monohydrate had to be recrystallized under sterile conditions. To provide the sterile bulk, the prednisolone t-butylacetate monohydrate was dissolved in A, 7V-di methyl acetamide (DMAC), filtered under sterile conditions, and crystallized with sterilized water. Experiments had shown that the solid phase in contact with the saturated solution was indeed the monohydrate. The material was filtered, washed with... 

This chapter focuses on the preparing and filling of injectable solid bulk pharmaceutical formulations. The material presented is general in nature but with references to direct the reader to more in-depth treatment of the subject matter. Coverage includes sterile bulk product preparation. 

X ray processing is now a practicable and economically competitive technique. X ray processing is a relatively new irradiation method which can be used for various applications where greater penetration would be beneficial, such as sterilizing medical devices, preserving foods, curing composite structures and improving the properties of bulk materials. 

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. 

UHMWPE comes from a family of polymers with a deceptively simple chemical composition, consisting of only hydrogen and carbon. However, the simplicity inherent in its chemical composition belies a more complex hierarchy of organizational structures at the molecular and supermolecular length scales. At a molecular level, the carbon backbone of polyethylene can twist, rotate, and fold into ordered crystalline regions. At a supermolecular level, the UHMWPE consists of powder (also known as resin or flake) that must be consolidated at elevated temperatures and pressures to form a bulk material. Further layers of complexity are introduced by chemical changes that arise in UHMWPE due to radiation sterilization and processing. 

Processing methods can have a major impact on the success or failure of a cardiovascular biomaterial. As described previously, surface features (either deliberately introduced or as the result of machining or tool imperfections), residues (from cleaning, handling, or sterilization), or process aids (either as surface residues or as bulk material diffusing from the biomaterial) can change the biological results. 

In premises for aseptic preparation from sterile raw materials the preparation room usually is combined with the fiUing room because carrying the bulk product into another room will introduce an additional contamination risk. In this situation a separate room for preliminary operations, e.g. disinfection of utensils and surfaces of containers, is required. 

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. 

Three-dimensional processing of materials by electron beam to produce uniform isotropic irradiation of components, which are to be sterilized or bulk/surface modified. ... 

The entire surface of the laminate is sterilised with hydrogen peroxide before it is filled and shaped into packs. This has proved to be a very efficient and safe technique. The filling takes place in a sterile environment which is small and has few moving parts. These are important factors that contribute to the integrity of the system. The packs are sealed through the liquid, which means they are completely filled and the contents are thus fully protected against oxidation. The brik format makes very effective use of materials and economical use of bulk volume in palletisation and distribution 93% is product and only 7% is primary and secondary packaging. 

Final product isolation in a form suitable for further processing into the final dose form of the pharmaceutical, e.g., as a tablet or an injectable solution. Secondary production of this type is sometimes done in a separate facility, with the raw material referred to as the bulk product or, more recently, the active pharmaceutical ingredient. Examples of unit operations at this stage of processing include lyophilization, precipitation, or crystallization followed by solid isolation using filtration and drying techniques. In some cases, the final product must be produced in a sterile form, which introduces additional complications when selecting suitable process equipment. 

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