Sterilization process sterile filtration

Adsorption of t-PA to process equipment surfaces consisting of either stainless steel or glass was minimized by adding the detergent polyoxyethylene sorbitan monooleate (Tween 80) to the semm-free culture conditioned media at 0.01% (vol/vol). The equipment was also rinsed, before use, with phosphate buffered saline (PBS) containing 0.01% Tween 80. Hydrophilic, plastic equipment was used whenever possible. AH buffers were sterile filtered. Sterile filtration of Hquids and gases is usually carried out using 0.2 or 0.45 p.m filters. 

Sterile Filtration of Gases. Primary appHcations for sterile gas filtration are the sterilization of fermentor inlet air, fermentor vent gas, vents on water for injection tanks, and vacuum break filters during lyophilization. Operational and process considerations apply. Typically, the membrane in gas... 

Downstream Processing Microfiltration plays a significant role in downstream processing of fermentation products in the pharmaceutical and bioprocessing industry. Examples are clarification of fermentation broths, sterile filtration, cell recycle in continuous fermentation, harvesting mammahan cells, cell washing, mycelia recovery, lysate recovery, enzyme purification, vaccines, and so forth. 

All production processes, such as ampoule washing and sterilization, solution filtration, equipment set-up and operation, sorting, and freeze-drier cleaning and operation, should be covered in detail in a procedure manual to ensure that all operations are understood as well as carried out properly and uniformly. Cleaning, sterilization, sterile filtration, filling, and aseptic processing operations must be validated. 

Particular attention should be paid to nonstandard production technologies including nonstandard methods of sterilization, sterile filtration and aseptic processing, lyophilization, microencapsulation, and certain critical mixing and coating operations. With such processes pilot-scale manufacture may not be predictive of industrial scale manufacture, and data on three full-scale production batches may be required in the application. 

Where terminal processing is not possible, the justification for alternative sterilization methods will be included in the EPAR, or at least a statement to the effect that sterile filtration/aseptic processing will be used. Presterilization bioburden issues that arose during the assessment will be included in the EPAR. 

Compoimding pharmacists routinely use in-process sterilization, such as sterile filtration, or terminal sterilization, such as autoclaving or dry-heat sterilization. In some situations, combinations of these methods may be used along with chemical sterilization. 

Downstream processing is normally undertaken under clean room conditions, with the final steps (e.g. sterile filtration and aseptic filling into final product containers) being undertaken under Grade A laminar flow conditions (Figure 3.18). 

The stoppers and primary contact filling equipment are transferred from the sterile storage area into a filling room. Eor the filling process, the filtration set-up and filling equipment are aseptically assembled under class 100 conditions in the filling room. 

The units used for growth testing must be subject to the same processing steps (e.g., cleaning, depyrogenation, sterilization, filtration, filling, lyophilization, reconstitution) up to the point at which they are placed into incubation. 

Gases - [AIRPOLLUTION CONTROLMETHODS] (Vol 1) - [COAL CONVERSION PROCESSES - GASIFICATION] (Void) -m air pollution models [ATMOSPITERIC MODELING] (Vol 3) -analysis by multiphoton ionization [SPECTROSCOPY, OPTICAL] (Vol 22) -as lubricants [LUBRICATION AND LUBRICANTS] (Vol 15) -sampling of [SAMPLING] (Vol 21) -sterile filtration [MICROBIAL AND VIRAL FILTRATION] (Supplement)... 

Even at this low alcohol level microbiological spoilage is a hazard. Suggested manufacturing processes are benzoic acid preservation with either sterile filtration or flash-pasteurisation of the syrup, or in-pack pasteurisation. 

This section will concentrate on that portion of the aseptic process wherein the drug product is sterilized by filtration. From the earlier discussion, sterile filtration is perhaps a misnomer, since the sterile filtrate is almost always processed further under aseptic conditions, which involves a risk of contamination [44], Therefore, to speak of drug product sterilization by filtration as being as final a processing step as the steam sterilization of a product could possibly lead to erroneous assurances or assumptions. Since a sterile filtrate can be produced by filtration, however, we will continue to refer to the process as product sterilization by filtration. 

The complexity of the sterile filtration operation and the CGMP regulations require the validation of sterilizing filter systems. The validation of a sterile filtration operation can be complex, with many operational parameters and their interactions needing to be identified, controlled, and predicted for each end product to demonstrate that sterility is adequately achieved by the filtration process. In the commonly used steam sterilization process, the heat parameters are identified and in-process controls specified such that a level of sterility assurance can be reproducibly obtained. In steam sterilization, the important parameter of heat, measured by temperature, can be accurately measured and continuously monitored to ensure the operational integrity of the autoclave however, unlike steam sterilization, filtration sterilization cannot be monitored on a continuous basis throughout the process. 

In all fermentation processes, it is necessary to have contamination-free fermentation media and seed cultures. Liquid sterilization of the fermentation medium is conducted by two means.1011 Contaminating microorganisms can be removed from fluids by filtration. With improvements in membrane technology, sterile filtration is finding wider use, but can only be used with completely soluble media. 

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