Aseptic processing environmental monitoring

Media fill failures are investigated in accordance with manufacturing site SOPs. The investigation may include, but is not limited to, a review of the aseptic fill data, review of the environmental monitoring data, review of the component sterilization results, review of all intervention activities, and identification of the contaminants found. Also, additional media fills may be performed to demonstrate that the area and processes are under aseptic control. If the system cannot be shown to be under control, product produced subsequent to the media fill failure on that fill line will be placed under management review for final disposition. 

To demonstrate the control of aseptic operations maintained by well-trained personnel, defined procedures, and appropriately designed equipment and facilities. Media filling in conjunction with comprehensive environmental monitoring will be conducted three times to demonstrate that the aseptic processing of lyophilized powder is functioning as intended. 

It is easily understood that if the aseptic operation is performed in a separated small space from which personnel have been completely excluded, the necessity for room classification based on particulate and environmental microbiological monitoring requirements may be significantly reduced. In other words, critical operations in an aseptic area should be performed in the smallest space, and intervention by personnel should be minimized by indirect means through the use of protective glove ports and/or half suits. Application of these methods can minimize the chance of contamination. Following are such systems currently in place to reduce the contamination rate in aseptic processing. 

There are items that must be transferred into the aseptic processing area that cannot be treated within a sterilizer/oven. These include portable tanks, electronic equipment, and containers of sterile materials (ready-to-use items, sterile powders, environmental monitoring media, etc.). Air locks, pass-throughs, and similar designs are employed in which the exterior surfaces of the items are disinfected. The disinfection process may be completed by personnel outside and/or inside the aseptic area depending upon the specifics of the design. 

TR 11 Sterilization of Parenterals by Gamma Irradiation, 1988 TR 13 Fundamentals of an Environmental Monitoring Program, 2001 TR 22 Process Simulation Testing for Aseptically Filled Products, 1996 TR 26 Sterilizing Filtration of Liquids, 1998... 

Routine Interventions. The execution of the aseptic process ordinarily requires a number of repetitive activities such as product and component replenishment, weight checking, operator breaks, and environmental monitoring. Each of these is a required part of the process, and cannot be eliminated. They should be included in the process simulation and performed... 

Equipment and components have improved in quality to the extent, that environmental monitoring may be the most invasive intervention during an aseptic process (an undesirable situation). 

Proceedings on the August 21, 2000 Environmental Monitoring Aseptic Processing Symposium, PDA, 2000. 

Lack of complete validation for aseptic processing. Poor practices by operators in aseptic areas. Inadequate environmental monitoring. 

Committee on Microbial Purity, Validation and Environmental Monitoring of Aseptic Processing, J. Parenteral Sci. Tech., 44(5) 272-277 (1990)... 

Responding to Monitoring Data Data from routine environmental monitoring programs are not suflicienl on their own to certify that all processes and conditions that might influence the sterility of products manufactured in the aseptic facility are satisfactory and under control. They are only one part of the overall system of sterility assurance. 

The environment to which the excipient may be exposed should be similar to that used in the manufacture of the final dosage form. This is especially true in the case of excipients intended for parenterals. For example, controlled areas may need to be established along with appropriate air quality classifications. Such areas should be serviced by suitable air handling systems and there should be adequate environmental monitoring programs. Any manipulation of sterile excipient post-sterilization must be performed as an aseptic process, including the utilization of Class 100 air and other aseptic controls. 

For sterile products, there should be no reduction in the degree of validation of sterilizing equipment required. Validation of aseptic processes presents special problems when the batch size is small, since the number of units filled may be not adequate for a validation exercise. Riling and sealing, which is often done by hand, can compromise the maintenance of sterility. Greater attention should therefore be given to environmental monitoring. 

Media filling in conjunction with comprehensive environmental monitoring of the aseptic area can be particularly valuable in evaluating the aseptic processing of sterile products. The media fill should simulate the aseptic process as far as reasonably practical. 

CFR 211.42 (3) states (design and construction features) requires in part, that aseptic processing operations be performed within specifically defined areas of adequate size. There shall be separate or defined areas for the firm s operations to prevent contamination or mix-ups. Aseptic processing operations must also include, as appropriate, an air supply filtered through high efficiency particulate air (HEPA filters) under positive pressure, as well as systems for monitoring environmental conditions. .. and maintaining any equipment used to control aseptic conditions. ... 

Just as with other aseptic preparation processes, a program of environmental monitoring and personal qualification for aseptic operation has to be carried out, see Sect. 31.6. 

All documents of batch numbers 001, 002, and 003 (process simulation of 24-hour duration) of media-fill study 1, study 2, and study 3 for aseptically filled A-ml vials were reviewed and found to meet the media-fill qualification requirements per current USP monograph and ISO 13408-1 1998 (E), including process simulation, environmental and personnel monitoring results. 

The fermentation process is operated under aseptic and optimum environmental conditions and ordinary temperature and pressure. In addition to the multicomponent culture broth, the concentration of each component contained in the culture broth is changed over the cultivation time. Therefore, heat resistance for steam sterilization and measurement specificity for the target compound are required for a monitoring system applied to fermentation process. 

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