Pharmaceutical Isolator Mode of Operation

Question: Describe about the Pharmaceutical Isolator for Mode of Operation. Answer: Design and operation of Isolator Systems: Isolators are designed to provide continuous and total isolation of the internal area of the isolator form the external environment. Following are the design considerations for the isolators : size, materials, mode of operation (manual or automatic), ergonomic mock up, material compatibility with the product to be sterilized, type of air flow (laminar or turbulent), control systems for the operation, transferability of equipment and type of products (tested or produced). Isolators are also designed to separate internal area from its operators also. Isolators work on the principle of the positive pressure. Full wall and considerable overpressure is useful in the physical and aerodynamic separation of the separation of the internal components form the external environment. There are two types of designs of isolator are available like closed and open operation. Isolators with closed design use aseptic connection to transfer material to auxiliary equipment. Isolators with closed design r emain closed during its operation. Isolators with open design possess openings for the ingress or outgress of the material. These openings are specifically designed using continuous overpressure to avoid entry of contamination inside the isolator chamber. Isolators with positive pressure design are being widely used and isolators with negative pressure design are being used for handling toxic products. Designs of the isolators with negative pressure are complicated because these types of isolators should satisfy two objectives. These objectives are sterility of the drugs inside the isolator and protection of the operator form the toxic material inside the isolator. Isolators with negative pressure are designed to have special buffer zone. This buffer zone can be used as exhaust for both incoming air in the room and outgoing positive pressure air. By virtue of this, sterile product gets protection from the contaminated air (Midcalf, 2004; Agalloco and Akers, 2016). Advantages: Advantages of the isolator system include: capability to sustain sterility of the equipment for considerably longer duration of time, isolator system is comparatively less expensive in terms of operation cost as compared to the other system like clean room, there are very less chances of sterility false positives due to use of isolator system and there is no requirement of gowning to the operator while using isolator system. Operating cost of isolator is lower as compared to the nonbarrier system. Isolators produce less environmental contamination as compared to the traditional cleanroom. Speed of air and exchange of air is also less in isolator as compared to the traditional cleanroom. This helps isolators in producing less environmental contamination as compared to the cleanroom. In terms of biodecontamination also, isolator has more advantage as compared to the cleanroom. In isolator, only drug and excipients used for the manufacturing comes in direct contact with the operating sy stem. On the other hand, in case of cleanroom human intervention is more in operating system Disadvantages: These isolators have higher capital cost as compared to the non-barrier systems. Time for the qualification of isolators is more as compared to the conventional cleanrooms. It reflects, there is need of additional requirements for qualification of isolator and there is no technical hurdle in its qualification. Isolators have limited flexibility and for its installation there is requirement of significant planning (Agalloco and Carleton, 2007; Coles, 2004). Sterilization processes and its recommendations: Different methods of sterilization used in pharmaceutical industry are dry heat sterilization, chemical sterilization, radiation sterilization and filtration sterilization. Dry heat sterilization kills microorganisms by denaturing proteins and nucleic acids. This dry heat sterilization is simple and cost effective method of sterilization of pharmaceutical products. This method can be useful for the sterilization of glasswares, non-aqueous thermostable liquids and thermostable powders. In radiation sterilization, ionizing and non-ionizing radiation like gamma and X rays can be used. These radiations create free hydrogen radicals, hydroxyl radicals and peroxide radicals which cause intracellular damage to microorganisms and kill them. UV radiation has the capacity to reduce airborne contamination in room by approximately 90 % during the period of 30 minutes. Pharmaceutical powders are more resistant to degradation by ionizing radiation as compared to the pharmaceutical liquids. Radiati on sterilization can be very useful in the sterilization of the thermolabile products like penicillin, streptomycin, thiamine, and riboflavin. Chemical sterilization incorporates use of exposure of materials to be sterilized to the gases like ethylene oxide, formaldehyde, glutaraldehyde and propylene oxide. Ethylene oxide is the most common sterilizing agent used and it acts by the alkylation. Ethylene oxide approximately takes 2 to 5 h at 55C to complete sterilization process. Ethylene oxide is specifically used for the sterilization of the gloves, plastic syringes and disposable needles. Ethylene oxide can be used to sterilize thermolabile pharmaceutical products like penicillin. However, products like thiamine, streptomycin and riboflavin lose potency upon exposure to the ethylene oxide. Filtration sterilization is widely used method for the sterilization of thermolabile products which gets degraded due to heat exposure of other method of sterilization. Filtration sterilization m ethods dont kill the bacteria but remove the bacteria form the material to be sterilized. In filtration sterilization method, material to be sterilized passed through the sterile filter and immediately transferred to the sterile container. Prefiltration of pharmaceutical products can be performed by depth and surface filtration to remove large particles. Different types of filters can be combined together for the effective sterilization. Filtration sterilization can be effectively utilized for the filtration of ophthalmic solutions and biological products. It can also be used for the sterilization of the air and gases to be supplied to aseptic area. Restricted Access Barriers (RABs) are designed to augment the aseptic operations to be carried out in the clean room. Mobile clean room can be used to carry out aseptic operations with more flexibility in the location (Aulton and Taylor, 2013; Jasti and Ghosh, 2004). Environmental monitoring and integrity testing: There is the provision of both viable and non-viable particle monitoring in the isolator system. Both viable and non-viable particle monitoring are the essential components of the isolator. These are not essential components of the sterility test isolator, however it is getting popularity in the recent times. Contamination control can be effectively controlled by the environmental monitoring. Shift of gloves use form the neoprene gloves to the hypalon gloves have dramatically decreased the contamination in case of isolators. In modern isolators, contamination due to gloves is in the same level of the airborne contamination recovery which is a measure of environmental monitoring. As there is very low level of contamination in isolators, intensity of environmental monitoring is very high. For finding small quantity, it is mandatory to evaluate more precisely. Due to difficulty in measurement of zero contamination and due to limitations of limit of detection (LOD), it is difficult to pe rform environmental monitoring in isolators. Isolator environment is extremely clean and there is possibility of getting contamination in not more than 10000 samples. It is not perfect to say isolators are sterile but these are safe enough. Approximately 1 ml sample is required over a period of four hours for the environmental monitoring in case of isolators. Active air sampling is more suitable as compared to the settle plates for environmental monitoring in case of isolators. Surface samples decontaminated with the Vapor-Phase Hydrogen Peroxide are not suitable because these samples are not going to give any type of results. Physical measures like air filtration system and pressure differentials are more valuable as compared to the evaluation of microbial contamination. Isolator performance can be more effectively monitored by evaluating total particulate count as compared to the microbial contamination. Environmental monitoring doesnt give exact data for the sterility. There is e xistence of pathogens which cant be detected by the environmental monitoring. Few pathogens exist in the environment, which are viable but cant be culturable. It reflects, these pathogens have metabolic activity but difficult to culture them (Agalloco and Akers, 2006; Katayama et al., 2008). References: Agalloco, J., and Akers, J. (2016). Advanced Aseptic Processing Technology. CRC Press. Agalloco, J. P., and Carleton, F. J. (2007). Validation of Pharmaceutical Processes. CRC Press. Agalloco, J., and Akers, J. (2006). Simplified Risk Analysis for Aseptic Processing: The Akers-Agalloco Method. Pharmaceutical Technology, 30(7), pp. 60-76. Aulton, M.E. and Taylor, K. M.G. (2013). Aulton's Pharmaceutics: The Design and Manufacture of Medicines. CRC Press LLC. Coles, T. (2004). Isolation Technology: A Practical Guide. CRC Press. Jasti, B. R. and Ghosh, T. K. (2004). Theory and Practice of Contemporary Pharmaceutics. CRC Press. Katayama, H., et al., (2008). Proposal for a New Categorization of Aseptic Processing Facilities Based on Risk Assessment Scores. PDA Journal of Pharmaceutical Science and Technology, 62(4), pp. 235-243. Midcalf, B. (2004). Pharmaceutical Isolators: A Guide to Their Application, Design and Control. Pharmaceutical Press.