Quality control of clean compressed air for pharmaceutical production

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1. Applications of compressed air in the pharmaceutical industry. Compressed air is widely used in the drug production process, such as in large-scale fermentation processes for vaccines, in the preparation of vaccine semi-finished products, in tanks used for mixing and diluting raw materials and solutions, for transferring and purging materials, for maintaining pressure after sterilization of process systems, and for controlling pneumatic components. Since the quality of compressed air that comes into direct contact with drug production directly affects the quality of the products, in order to ensure its quality, it is necessary not only to carry out strict purification processes on the compressed air but also to control its oil and water content. 2. Compressed air system 2.1 Composition of a clean compressed air system The compressed air and purification system generally consists of equipment for generating, processing, and storing compressed air; such a system is known as the air supply system, or air compression system. Functionally, a compressed air system can be divided into the following parts: 1) The part that generates compressed air: such as air compressors and their control systems, cooling water systems, etc ； 2) Compressed air treatment section: such as dryers, filters, oil removers, etc ； 3) Compressed air delivery section: such as air storage tanks, pipelines, valves, etc. 2.2 Working principle of the clean compressed air system: During compression and delivery, air inevitably comes into contact with machine components; therefore, the compressed air produced by air compressors may contain a large amount of harmful impurities, including water, water mist, water vapor, and condensed water ； Oils, including oil mist and oil vapor ； Various solid substances, such as rust sludge, metal powder, rubber dust, tar particles, and fine particles of filter materials and sealing materials ； There are also various harmful chemical odors and other such substances. If not removed using appropriate methods, it will not only cause damage to the air supply system but also have the following adverse effects in practical use: 1) Microorganisms and particles in compressed air can contaminate sterile products ； 2) Oil vapor mixed in compressed air accumulates to a certain extent, forming an explosive and flammable hazard; moreover, when lubricating oil vaporizes, it forms an organic acid that can easily corrode the inner surfaces of compressed air pipelines as well as pneumatic components ； 3) The tiny particles that get mixed in (such as dust, rust, etc.) can easily damage pneumatic components and clog the throttle holes; more seriously, they can cause severe contamination of the material ； 4) The moisture mixed in compressed air will reach saturation and precipitate as water droplets under certain temperature and pressure conditions; when compressed air comes into contact with the material, it can easily have a serious impact on the quality of that material ； 5) Excessively high compressed air temperature and the formation of water pose an absolute threat to the production of vaccines and bacterins. 3. Quality standards for clean compressed air 2.1 Quality grades for compressed air In order to standardize these requirements, the Committee on Air Compressors, Pneumatic Machinery and Tools (TC118) under the International Organization for Standardization (ISO) established international standards in 1986 regarding devices for drying and purifying compressed air as well as the quality of compressed air. The ISO standard ISO8573.1 classifies contaminants in compressed air into three categories: solid impurities, water, and oil. China has adopted ISO8573, which is reflected in the standard GB/T13277‑91 «Quality Grades for Compressed Air for General Use». In 2001, the ISO standards organization revised ISO8573.1, with the main changes relating to the requirements for solid particles. The new standards specify the quantity of solid particles; this change takes into account the actual performance of fiber filters, and it is also relatively easy to detect, as shown in Table 1. 2.2 Enterprise Quality Standards for Clean Compressed Air. At present, there are no official international or national quality standards for clean compressed air used in pharmaceutical production. By referring to the aforementioned quality grade standards as well as the GMP requirements regarding air cleanliness, and by conducting a comprehensive assessment of these qualities along with the actual needs of enterprises and the available testing methods, enterprise-specific quality standards for clean compressed air have been established. 3. Quality testing of compressed air used in pharmaceutical production. The testing of compressed air primarily includes: particle count, microbial count, oil content, and moisture content. 3.1 Testing of oil content in clean compressed air: Taking Germany’s Drager Aerotest Simulan as an example, the measuring device is connected to the air outlet from which the clean compressed air is supplied. The gas valve is opened slowly to flush the measuring device for 2–3 minutes. The moisture content testing tube marked “Oil Vapour” is cut at both ends using a tube cutter, and then the oil content testing tube is inserted into the support tube marked “Oil” on the measuring device. After waiting for 5 minutes, the testing tube is removed from the device, the protective film is removed, and an additional 1 minute is waited. The oil content is determined based on the color change of the indicator layer. The gas is considered qualified if the oil content is <0.1 mg/m3. 3.2 Detection of moisture content in clean compressed air: Using the same method as for oil testing, cut both ends of the moisture content detection tube marked “Water Vapour” with a tube cutter. Insert this detection tube into the support tube marked “H2O” on the measuring device. After waiting for 10 minutes, remove the detection tube from the measuring device and determine the moisture content in the gas by observing the color change of the indicator layer. The gas is considered acceptable if its water content is <100 mg/m3. 3.3 Detection of microorganisms: An air suspension bacteria sampler is used to collect 1000 L of biological particles suspended in the air and place them on soybean protein agar plates. These samples are first cultured at 20–25°C for 72 hours, and then at 30–35°C for another 48 hours, until a visible number of colonies have formed, after which they are counted. The concentration of suspension bacteria at each testing site must be below 1 cfu/m3. The above is the recommended post-treatment flowchart. Therefore, there is no certainty regarding the use of compressed air in pharmaceutical applications, and the quality of gas required varies depending on the manufacturing process; however, minimum standards must be maintained. At present, drug safety remains an issue that cannot be ignored. Compressed air in the pharmaceutical industry plays an extremely important role in drug quality. The many problems that currently exist in design, construction, and operation management should draw serious attention from the relevant authorities, who should gradually standardize practices based on the actual conditions in each stage. Furthermore, as the level of automation increases and unmanned operation becomes feasible, the biggest source of pollution from compressed air will surely be eliminated, thereby ensuring the sterility of clean rooms on a fundamental level. Furthermore, further optimizing the compressed air system in the drug production process by upgrading it to be more efficient and clean, thereby improving its operational efficiency, will be an important task that brings significant economic and social benefits.