On the use of ozone in disinfection and sterilization of pharmaceutical plants

1 Using HVAC to disinfect the clean area is the basic regulation of pharmaceutical enterprises in China Pharmaceutical enterprises with different dosage forms should do a good job of validation according to the national regulations Ozone sterilization is one of the recommended sterilization methods in GMP management of Chinese pharmaceutical enterprises There are three traditional sterilization methods: one is ultraviolet sterilization, the other is reagent sterilization, the third is heating sterilization These methods have been used by people, and their safety and reliability have been confirmed by long-term practice, but they also have their own defects Ultraviolet rays kill bacteria by light wave radiation The light wave propagates in a straight line, and its irradiating intensity is inversely proportional to the square of the distance Therefore, only when it reaches the irradiating position and reaches the irradiating standard can it have the bactericidal effect, and the bactericidal ability of all UV lamps decreases with the increase of using time The main problems of UV sterilization are: its Chuangtou ability is small, and its disinfection effect is not good in places where the UV can not reach; its sterilization ability decreases with the increase of use time, and the lamp has short life, too frequent replacement and high operation cost Chemical reagent sterilization has a strong smell of medicine, which can not be discharged naturally It needs air conditioning to replace the fresh air for a long time, so it increases energy consumption At the same time, there is secondary pollution Because the remaining medicine is discharged into the air directly, it will cause pollution to the surrounding environment For example, formaldehyde fumigation, operation trouble, long fumigation time, secondary pollutants, has certain harm to renti It takes 8 hours to do a formaldehyde fumigation, and there are many residues attached, so it is not suitable to remove them Ozone disinfection is a good way to replace them The method is to place the ozone generator directly in the air duct of the air conditioning purification system, which is called the built-in ozone generator With the air flow of the air duct, ozone is sent to each clean area for disinfection and sterilization The remaining ozone is inhaled into the air outlet and taken away by the central air conditioner The ozone generator can also be placed outside the air outlet of the central air conditioner, and the ozone can be injected into the air duct of the central air conditioner, and then sent to each clean room, which is called the external ozone generator The external ozone generator is easy to install and maintain, but the manufacturing cost is higher Both methods have the same disinfection effect According to the requirements of disinfection technical specifications of the Ministry of health, the ozone concentration of air disinfection is 5ppm, but in fact, the disinfection of clean area is not only the disinfection of air, but also the disinfection of object surface Therefore, the concentration in the design should generally be greater than 10ppm Start up for 1-2 hours before going to work and 1 hour after going to work every day to ensure that the floating bacteria and settling bacteria in the clean area can meet the requirements of GMP It can be seen from the test reports of pharmaceutical factories using ozone for sterilization that all bacteria tests are qualified Completely replaced the headache of formaldehyde fumigation disinfection At the same time, the non production operation is reduced, the energy consumption is reduced, and the satisfactory effect is obtained Fsy-k series products specially designed by Zhongao company can rapidly transfer ozone to all places in the space, which can be controlled by computer regularly, without dead angle, easy to move and use, and can reach class 100 cleanliness In pharmaceutical plants, generally speaking, the clean area is large, and the central air conditioning purification system is used to complete the purification and disinfection of each clean area The method is that the ozone generator is directly installed in the main air supply and return pipes of the central air conditioning purification system or the back end of the medium efficiency filter in the purification air conditioning box, and the power control box is placed in the machine room During disinfection, close about 90% of the fresh air inlet valves and external discharge valves, so that the HVAC system and the clean area form an internal circulation state It only takes about 1-1.5 hours for air sterilization every day, and 2-2.5 hours for fumigation instead of chemical reagent The advantages of the scheme are as follows: using the purified air as the carrier of ozone (about 60m3 air volume per minute can pass through the ozone generator), the ozone can quickly spread to the clean room controlled by the HVAC system, and the ozone concentration is evenly distributed The sterilization purpose of the clean room can be achieved without adding any disinfection equipment in the clean area; at the same time, the HVAC system can be killed Effect of mixed bacteria and mould In practice, it is found that ozone can also play a role in dissolving bacteria and extending the service life of the filter 2 Concentration standard of ozone applied in central air conditioning system of pharmaceutical industry According to Section 8.2 of section 4.12 ozone application of technical specifications for disinfection issued by the Ministry of health in December 1991, "ozone with concentration of 5-10mg / m3 (equivalent to 2.5-5ppm) is used for 30 minutes for airtight air; 20-30mg / m3 is required for settling colonies on the surface of objects , (equivalent to 10-15ppm) " The purpose of ozone application in pharmaceutical industry is to replace ultraviolet and chemical fumigation, and to disinfect the settling colony on the surface of air, mechanical equipment and medium materials in the whole clean area The required ozone concentration is 10-15 ppm, which is equivalent to 20-30 mg of ozone per cubic meter of air 3 The calculation method of ozone application amount of air conditioning system: set V1 as the space volume of clean area, V2 as the space volume of HVAC system, V3 as the loss of ozone caused by fresh air supplemented by maintaining positive pressure of clean area, then the total volume of sterilization space (V) is calculated as: v = V1 + V2 + V3 Determination of V3: according to the practice, the more reliable empirical formula is summarized as follows: V3 ≈ total circulating air volume of HVAC system m3 / h * 25% (replacement rate of conventional fresh air) × 10-20% (fresh air volume supplemented by maintaining positive pressure in clean area) × 39% (budget value of ozone half-life when ozone is applied), that is, V3 = total circulating air volume of HVAC system × 1-2% Selection of ozone generator: firstly, determine the concentration of ozone sterilization according to the efficiency of ozone sterilization, i.e according to the standard of technical specifications for disinfection (c): for the floating bacteria in the air, the concentration of ozone sterilization is 2-4ppm; for the settling colonies on the surface, the concentration is 10-15ppm (refer to technical specifications for disinfection) The natural half-life (s) of ozone is about 23 minutes in reference state, and the decline rate of one hour is 61% Design: when ozone sterilization is applied for 60min and reaches the required concentration, it can be kept for a period of time (1-1.5H) to get the effect of complete killing of settling colonies on the surface of mechanical equipment and building objects, so as to achieve the effect of chemical fumigation For example, the total volume of sterilization space (V) is 1000m3, and the sterilization requirement is to replace chemical fumigation for large-scale disinfection, and sterilize the settling colony on the surface of equipment and building objects According to the above requirements, the ozone concentration (c) in the air shall be more than 10 ppm (converted to 19.63 mg / m3 in the working state) The ozone natural decline rate (s) of the ozone generator after one hour of operation is 61% The ozone generation of the machine shall be selected as g / h (W): w = CV / (1-s) = 19.63 × 1000 / (1-61%) ≈ 50.33 (g / h) The ozone generator with an hourly output of 50 g can be selected 4 Disinfection and application of ozone in pharmaceutical plants: (1) disinfection and sterilization of space For clean rooms other than the central air conditioning purification system, or other rooms that need to be sterilized, they need to be sterilized separately The method is to select ozone generator and install it directly in the room According to the need to set disinfection time, disinfection will automatically shut down, so it is very convenient to use Select and use according to the size of room space volume As long as the requirements of ozone concentration are met, the goal of disinfection and sterilization can be achieved It is much easier than fumigation of room with chemical reagent It can completely replace chemical fumigation, shorten disinfection time and avoid secondary pollution (2) in the process of pharmaceutical production, the surface disinfection and sterilization of articles often needs to be carried out on raw materials, tools and equipment, packaging materials, production sites, etc The traditional method is to use ultraviolet disinfection, but the disinfection is not complete, there are many disadvantages such as disinfection dead angle, fast attenuation, for certain bacteria in a specific environment can not be killed and so on According to the technical specification for disinfection, the bacteria on the surface of the object immersed in ozone gas can be killed after contacting for a period of time （3） There are many places where water is used for disinfection and sterilization in pharmaceutical plants, such as medical water, disinfection water, cleaning water and drinking water According to different water quality requirements, different technological processes are adopted, and general ozone water treatment methods are used for disinfection process to achieve satisfactory results.