Sterilization raw materials

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. 

Inoculum from seed fermenters and sterile feeds are transferred to the fermenter by air pressure. Centrifugal pumps (316 S/S) are used to pump non-sterile raw materials, slurries, harvested broth, etc. The centrifugal pumps and piping should be cleaned immediately after a transfer has been completed. Occasionally a specialty pump may be required. 

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. 

Sterile products subject to neither filtration nor terminal sterilization, are produced from sterile raw materials and packaging components in an aseptic area... 

During these operations, the state of the premises, the environment and the operating conditions must be such that the material sampled is not contaminated and that it does not contaminate others. This necessitates special requirements in the case of sterile raw materials or hazardous products. 

Sterile raw materials must be weighed and dispensed in the sterile compounding areas in which they will subsequently be stored and used. 

Stock culture contaminated , foreign microorganisms in culture stock/contami-nated inoculation flash/wrong sterilization procedure/temperature and pressure instruments wrong/air left in sterilization chamber/sterile area contaminated/ cotton plugs contaminated/[faulty sterilization] /raw material contaminated with spores combined with inadequate germination-sterilization. 

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. 

The quality of and access to raw materials, in particular the lipid sources used Sterility (for injectables)... 

Such sterilization procedures (see also Chapter 20) may include heat treatment, filtration, irradiation, recrystallization flxm a bactericidal solvent such as an aleohol, or for dry products where eompatible, ethylene oxide gas. If the raw material is only a minor constituent and the final product is adequately preserved either by lack of chemically... 

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. 

Ethylene oxide is used in the manufacture of raw materials and can be used to sterilize the surface of finished products and containers. Unfortunately, ethylene oxide is a genotoxic carcinogen and its use is not accepted without justification. In any event, tight controls are required on residues of ethylene oxide and its halohydrin-related substances. For raw materials the amount of these residues is limited to 1 and 50 pig/g, respectively for finished products 1 and 50 pg/g, respectively (with any affected ingredients subject to the control limits for raw materials) and for containers, based on simulated use, 1 and 50 pg/mL container volume, respectively. 

In this level, the fundamental tasks required to convert the raw materials into the final product are identified. All tasks are related to property differences. Siirola (1996) has presented the following hierarchy of property differences molecular identity, amount, composition, phase, temperature/pressure, form. This list of tasks is not very well suited for food properties. Common tasks for food processes are decontamination (e.g. pasteurization and sterilization) and structure formation (e.g. emulsification, size reduction of dispersed phase in an emulsion, crystallization, interfacial adsorption/desorption). 

Equipment, raw materials, intermediates, finished products, and packaging materials may require sterilization. A discussion of the sterilization process is presented in Section 9.6.4. 

Raw Materials Bovine Serum Sterilization Culture Growth... 

The tests for microbial limits and recommendations for microbial quality criteria of raw materials, excipients, drug substances, and pharmaceutical products have been established in pharmacopoeial compendia for over 30 years. These tests are listed in the USP 24 Chapter (61) Microbial Limits Tests and in the Ph. Eur. 3rd ed.. Biological Tests 2.6.12 and 2.6.13, Microbial Contamination of Products Not Required to Comply with the Test for Sterility (total viable count, tests for specified microorganisms) and the JP XIII 30 Microbial Limit Test. 

In summary, water can be a source of contaminants. If the raw material (drinking water) complies with the quahty parameters established by authorities, contaminants still present can be eliminated by usual water purification processes available to the pharmaceutical industry. While distillation and reverse osmosis provide water with the quality specifications for purified water and highly purified water, WFI is generally obtained by membrane filtration (associated with another purification process) not only because of chemical contamination but mainly because of sterility requirements. 

Water is the most common raw material used, and it is recommended that the manufacturer fully comply with the standards of at least purified water for inclusion in the formulation, though there is no requirement. Efforts should be made to provide as much microbial-free water as possible this can be readily achieved by installing a loop system in which the incoming water is first subjected to ultraviolet sterilizer, carbon filter, demineralizer, and a... 

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