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Abstract: The quality control requirements and practices for medical oxygen are discussed from several key aspects, including the selection of medical oxygen production processes, raw material supply, raw material transportation and storage, medical oxygen cylinders, and the inspection of medical oxygen products. Keywords: medical oxygen ； Production process selection ； Raw material transportation and storage ； Medical oxygen cylinder ； Quality inspection of medical oxygen products ； Reasons for excessive alkaline substance content and treatment measures: The issuance and implementation of GB 8982—1988 \"Medical Oxygen\" marked the introduction of industry-based administrative management for medical oxygen in China, ensuring the safety and effectiveness of medications used by the public. In 1998, **this standard was further revised and improved. Now, medical oxygen is included in the scope of drug regulation as an excipient in formulations. I am a technical manager in the oxygen production field at a metallurgical enterprise, and I have gradually gained some experience in the development and production management of medical oxygen. I would like to share my personal views on several key aspects of medical oxygen quality control, in the hope of contributing to further discussion. I. Selection of the medical oxygen production process. According to GB 8982 — 1998 \"Medical Oxygen\", \"this standard applies to gaseous oxygen and liquid oxygen produced by separating air using the cryogenic method\"; \"Oxygen produced by cryogenic distillation shall not be used if it is subsequently compressed in compressors whose piston seals are made of fluoroplastics or other materials that have not been approved by medical supervision authorities.\" ”Therefore, the common production processes for medical oxygen in China are as follows: 1. Cryogenic air separation equipment (referred to as cryogenic oxygen generators) → liquid oxygen → liquid oxygen pump → vaporizer → filling system → medical oxygen cylinders; 2. Cryogenic oxygen generator (with internal compression) → high-pressure, room-temperature gaseous oxygen → filling system → medical oxygen cylinders; 3. Liquid oxygen → liquid oxygen storage tank → liquid oxygen pump → vaporizer → filling system → medical oxygen cylinders; 4. Liquid oxygen → liquid oxygen storage tank → liquid oxygen pump → vaporizer → hospital centralized oxygen supply system. The first process is commonly used by companies that already possess large-scale air separation equipment and wish to develop by-products; by adding liquid pumps, a filling system, and medical oxygen cylinders, along with obtaining a pharmaceutical production license, they can start production immediately. This approach requires less investment and yields quick results. The second process is an air separation process specifically designed for the production of medical oxygen, such as those developed and produced by Hangzhou Oxygen Generator Factory. It is more suitable for new companies engaged in the production of medical oxygen; it requires a larger initial investment and a longer construction period. However, all the necessary processes and equipment are available from the start, there is no need to purchase raw materials externally, and production is not affected by external environmental factors. The third process is suitable for small or individual medical oxygen production units; it requires low investment and yields quick results. However, a long-term and stable supply of raw materials is needed, so production is affected by the availability of such materials. The fourth type is the latest centralized oxygen supply system for hospitals, which is adopted by large and medium-sized hospitals due to its low cost, simplified management, and reliability. This system requires low investment and simple operation; it only needs a stable long-term supply of raw materials, making it suitable for hospitals located near large oxygen production units. Furthermore, in China’s current medical oxygen production, there is still a production process specified in GB 8982—1998 \"Medical Oxygen\" that is no longer allowed. This process involves liquid oxygen → vaporizer → oxygen compressor → filling station → medical oxygen cylinders, or low-temperature oxygen generators → low-pressure oxygen → oxygen compressor → filling station → medical oxygen cylinders. Both of these processes were explicitly prohibited by the national standards issued in 1998 due to the use of fluoroplastic piston ring seals in the oxygen compressors. II. Raw materials: gaseous oxygen and liquid oxygen. According to the specifications of GB 8982 — 1998 \"Medical Oxygen,\" gaseous and liquid oxygen produced by separating air using low-temperature methods can be used as raw materials for manufacturing medical oxygen. Gaseous and liquid oxygen obtained through other oxygen production methods (such as adsorption, chemical, and membrane permeation methods) cannot be used as raw materials for medical oxygen production at present, as they have not been approved by relevant standards. It should be specifically noted that gaseous oxygen and liquid oxygen used as raw materials must pass the inspection methods specified in GB 8982—1998 \"Medical Oxygen\" before they can be used in the production of medical oxygen. Based on experience, the gaseous oxygen and liquid oxygen produced by large-scale low-temperature air separation units generally meet the requirements specified in GB 8982—1998 \"Medical Oxygen\" when tested using the prescribed methods; their oxygen content, moisture content, carbon dioxide content, carbon monoxide content, ozone and other gaseous oxides, as well as odor are all within acceptable limits. Only the content of gaseous acidic and alkaline substances poses a problem, with the level of alkaline substances tending to exceed the specified limits. This is caused by two factors: the quality of industrial circulating cooling water and the configuration of the low-temperature air separation process. In typical large-scale low-temperature air separation plants, air pre-cooling systems usually employ air cooling towers (see Figure 1). In air cooling towers, the air that has been compressed and heated comes into contact with the cooler industrial circulating water, allowing for thermal and mass exchange; as a result, the air is cooled and cleaned. Meanwhile, since the air comes into direct contact with the industrial circulating water, the quality of this water indirectly affects the quality of oxygen, which is the final product of air separation equipment. In industrial circulating cooling water systems, after make-up water is added to the system, the free and semi-bound acidic gas carbon dioxide in the water escapes into the atmosphere during aeration in the cooling tower, and thus the pH value of the cooling water gradually increases until carbon dioxide in the cooling water reaches equilibrium with that in the atmosphere. The pH value at this point is referred to as the natural equilibrium pH value of the cooling water. The natural equilibrium pH value of cooling water is usually between 8.5 and 9.3, falling within the slightly alkaline range. Due to the direct contact between air and slightly alkaline circulating water in air cooling towers, the air picks up the alkaline molecules from the water, resulting in the gaseous oxygen and liquid oxygen produced by air separation equipment having a slightly alkaline nature. If gaseous oxygen and liquid oxygen produced through this process are used as raw materials to manufacture medical oxygen, the resulting medical oxygen is also slightly alkaline; therefore, the alkalinity level will exceed the specified limits during testing. To this end, during the operation of circulating cooling water, enterprises must control its pH value. The pH of the water can be adjusted by adding acid to keep it within the range of approximately 7.0–7.6. Of course, such problems will not occur if there are no air cooling towers in the air separation process, or if groundwater with a pH value of around 7.0 is used in those cooling towers. It is recommended that medical oxygen production facilities request from suppliers a test report showing that the liquid oxygen purchased as raw material meets the standards specified in pharmacopoeias; it is best to acquire raw material liquid oxygen from manufacturers that hold a license for producing medical oxygen. III. Transportation and storage of liquid oxygen. The third and fourth medical oxygen production processes described earlier both involve the supply, transportation, and storage of liquid oxygen as the raw material. From the raw material supplier to the manufacturer, it must go through three steps: filling the tank with liquid, transporting it via liquid tank trucks, and filling the manufacturer’s liquid storage tank. The quality contamination of the raw materials that can occur in these three stages is multifaceted; for example, the impurity content in the liquid tankers and connecting pipelines, the medium used in the last filling of the liquid tankers, the medium used in the last filling of the raw material liquid oxygen storage tanks produced by the manufacturers, and the quality of the remaining liquid in those storage tanks. This requires companies to establish comprehensive operating and inspection procedures in production process management and to enforce them strictly; any lack of seriousness in any of these steps can lead to contamination of the liquid oxygen raw material. IV. Quality of medical oxygen cylinders. In addition to hospital centralized oxygen supply systems, the product packaging for medical oxygen consists of specialized medical oxygen cylinders. As a pressure cylinder, first: it must be managed, used, and regularly inspected in accordance with the regulations and standards related to the manufacturing, use, and inspection of cylinders, to ensure its safe and effective use. Second: Medical oxygen cylinders must be dedicated cylinders; they must under no circumstances be stored or used together with other types of cylinders, especially those containing air, inert gases, or flammable gases. This is to prevent unnecessary medical accidents resulting from incorrect selection of the gas contained in the cylinder. Third: To ensure that empty medical oxygen cylinders remain uncontaminated, manufacturers and suppliers should remind users to maintain a residual pressure of at least 0.5 MPa in the cylinders when returning them to the factory, thereby preventing backflow of air. Fourth: For medical oxygen cylinders, it is recommended that users use each cylinder specifically for its intended purpose, in order to prevent widespread circulation of these cylinders. This not only helps to ensure that the cylinders remain under the ownership of their respective units, but also avoids the risk of accidental filling or filling with substandard products during circulation, which could lead to contamination and damage of the cylinders. I recall receiving feedback in 2000 from a hospital client stating that patients experienced symptoms such as shortness of breath and nausea after inhaling the medical oxygen produced by my company. Upon analysis, the gas in the patient’s inhalation cylinder contained a small amount of moisture and had an iron-rust odor. Upon inspecting the cylinder, it was found that its inner wall was severely corroded, with a small amount of rusty liquid accumulated inside. It was learned that the hospital associated with this user had been filling its medical oxygen at another medical oxygen production facility before coming to our station. Since water is used to lubricate the compressors in that facility, water ends up being carried into the gas cylinders along with the oxygen gas; over time, this causes rust on the inner walls of the cylinders, ultimately leading to contamination of the oxygen gas and affecting its usability. I am responsible for the fact that no strict compliance was observed with the pre-filling inspection procedures before filling this gas cylinder, which led to such an avoidable quality accident. To this end, medical oxygen production units are specifically reminded to conduct thorough pre-filling inspections on cylinders of unknown origin or those they are not familiar with, and to proceed with filling only after confirming that the cylinders are qualified. V. Quality inspection of medical oxygen products: This is the final inspection before medical oxygen leaves the factory, and it is a crucial one as well. The national standard \"Medical Oxygen\" and \"Chinese Pharmacopoeia Part II: Oxygen\" provide detailed specifications and requirements regarding the inspection rules, as well as the testing methods for medical oxygen. The differences between them are as follows: 1. In GB 8982 — 1998 \"Medical Oxygen\", the required oxygen content is ≥ 99.5% V/V, whereas the Pharmacopoeia requires it to be no less than 99.0% V/V. 2. GB 8982 — 1998 \"Medical Oxygen\" adds requirements regarding moisture content; the purpose of this is to control the level of dryness in medical oxygen cylinders, thereby ensuring that the quality of the medical oxygen does not suffer as a result of excessive moisture in the cylinders or corrosion of those cylinders. 3. Regarding the methods for determining the contents of gaseous acidic and alkaline substances, GB 8982—1998 \"Medical Oxygen\" adopts both the methyl red indicator method and the mixed methyl red and bromothymol blue indicator method; both methods are equally effective, whereas the pharmacopoeial oxygen standard uses only the latter method. Based on the results of our actual testing, the acceptable range for the latter’s measurements is narrower than that of the former; therefore, it can be concluded that the latter provides better measurement accuracy. In general factories, the gas cylinders to be inspected need to be moved to the laboratory for testing. Our factory adopts the following approach: two analytical copper tubes for instruments are laid from the medical oxygen filling station to the laboratory as dedicated lines for medical oxygen analysis. Threaded connectors corresponding to the gas cylinders and oxygen pressure regulators are installed on the side of the medical oxygen filling station, while precision pressure regulators and gas flow meters are installed on the laboratory side; see Figure 2 for details. This eliminates the hassle and safety risks associated with moving gas cylinders, while ensuring speed, directness, and reliability. During the analysis, the inspector records the serial number of the gas cylinder under inspection at the filling station, opens the valve of the cylinder to allow gas to flow in, adjusts the pressure, and after purging the pipeline, proceeds with the inspection. Over the past two years, while working in the production of medical oxygen, I have gained some experience in production and quality control. Thanks to our focus on quality and strict management practices, we successfully passed the revalidation inspection for production licenses of pharmaceutical manufacturers in 2000. These are my humble opinions; I earnestly invite colleagues to offer their criticism and suggestions.