Sterility testing and manufacturing can also be performed inside isolators [40]. An isolator is a device that creates a controlled environment in which to
conduct sterility test or aseptic manufacturing. Isolator systems have different sizes. They can be the size of a glove box or an entire room. They are sealed or supply air through a microbial retentive filter and are able to be reproducibly sterilized. Isolators do not exchange air with the surrounding environment. They are completely enclosed HEPA-filtered chambers interfacing with a vapor-phase hydrogen peroxide (VHP) sterilizer and/or steam sterilizer. When closed, it uses only sterilized interfaces or a specialized rapid-transfer port (RTP) for material transfer. When open, it allows the transfer of mate- rials through a defined opening that has been validated and designed to preclude the entry of contamination. Isolators are constructed of flexible plastics, rigid plastics, glass, or stainless steel. They protect the test article by limiting direct contact between the analyst and the samples. All transfers are performed in an aseptic fashion while maintaining complete environmental separation. Aseptic manipulations are performed in half suits, which are flexible components of the isolator wall. The suits allow the operator a full range of motion within the isolator, or by gloves and sleeves. Operators are not required to wear special clean room clothing for conducting testing within isolators. The interior of the isolator is treated with sporicidal chemicals that result in the elimination of viable microorganisms. The air system in the isolator is processed microbial retentive filters (HEPA). The isolator meets the particulate air quality requirements of class 100 area but no requirements are needed for air velocity or exchange. Although the system is air leak-proof, it is not impermeable to gas exchange with the surrounding environment. Iso- lators are attached to sterilizers to enable direct transfer of solutions, sterile media, supplies, etc. RTPs or doors enable isolators to be connected to one another so that supplies can move aseptically. A compressed gasket assembly provides an airtight seal preventing microbial contamination. To switch to a sterility test using isolators, product validation must be performed. Testing will be more time-consuming when compared to the regular sterility test. 14. CONCLUSION
When validation studies are conducted, there are more variables to control in aseptic processing than in terminal sterilization. Process control allows the continuity, reproducibility, and optimization of a sterile procedure and test. Terminal sterilization provides a higher level of sterility assurance and easier validation and documentation process. However, because of their sensitivity to heat and package integrity, a large number of drugs are manufactured by aseptic processing. Aseptic processing provides a reliable process for manu- facturing of heat-labile compounds. However, process control of aseptic processing is more rigorous and complicated than terminal sterilization. Process control optimization comprises a continuous and reliable environ-
mental monitoring program along with sterility testing of finished products. Sterility testing is an important component in the process control of sterile manufacturing. On the basis of the sample chemical composition and anti- microbial nature, validation studies qualify the media and conditions for optimal microbial recovery. Process control and optimization of sterile pro- cesses and testing rely on the proper validation, training, and documentation of all procedures to comply with GMP.
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