Practical Techniques of Preloading Culture Medium Plate with Finished Products
How can we control human pollution?
First of all, GMP training for personnel. Personnel engaged in preparation operations and drug testing should undergo professional and technical training, with basic theoretical knowledge and practical skills. All preparation operations and drug testing personnel with special requirements should also undergo corresponding professional and technical training. All personnel engaged in preparation work should be familiar with GMP specifications.
Secondly, access to the clean room (area) is limited to the staff in the room and approved personnel. Personnel entering the clean room (area) are not allowed to wear makeup and accessories, and are not allowed to directly contact medicines with bare hands. Personnel entering the clean area should have health records and have a physical examination at least once a year. Patients with infectious diseases, skin diseases and those with wounds on the body are not allowed to engage in work related to product production.
Third, cleanroom personnel are regularly trained on the basic theory of microbiology and related sources of contamination, and on the correct way to wear sterile clothing.
Aseptic operation, for example: the speed of the activity during operation, the operating range and indoor air flow direction, the contact of sterile materials or items, the method of sampling and disinfection. It should also include cleanroom operation safety, cleanroom cleaning and maintenance, and pay attention to personal hygiene.
(2) Pollution of facilities and equipment
Facilities are rarelymicroorganismInherent sources. However, design flaws, poor structural materials, and incorrect operation can also have a significant impact on contamination levels, and equipment and other sources together constitute a source of contamination.
The new equipment can be designed to minimize internal sources of microbial contamination, thus achieving a level of hygiene. Conversely, microbial control of these devices is very difficult to solve.
In addition to the microbial contamination caused by the design of the equipment, explain the cleaning of the equipment. After each process of pharmaceutical production is completed, cleaning the pharmaceutical equipment is a necessary means to prevent drug contamination and cross-contamination. After the production of the product, there will always be a number of raw materials and microorganisms left behind. Microorganisms can multiply in large numbers with the organic matter in the residue as nutrition at appropriate temperature and humidity, producing various metabolites, thus greatly increasing the complexity and harm of the residue. If these residual raw materials, microorganisms and their metabolites enter the next batch of production process, they will inevitably have adverse effects on the next batch of products. Therefore, these sources of contamination must be removed from the cycle of pharmaceutical production through cleaning.
The cleaning methods of process equipment can usually be divided into manual cleaning methods and automatic cleaning methods. The characteristics of manual cleaning methods are that there are mainly manual cleaning tools, which are cleaned according to predetermined requirements, and the degree of cleaning is determined according to visual inspection until the cleaning is completed. The characteristics of automatic cleaning methods are that the entire cleaning process is automatically completed by automated specialized equipment according to certain procedures.
No matter what cleaning method is used, the key is to clean the difficult cleaning points of the process equipment, such as the cleaning of the batching tank, the bottom surface of the blades of the stirring paddle is the most difficult point to clean, and the flow rate of the cleaning water, temperature, cleaning time and other factors should be considered during cleaning verification. Finally, the SOP for cleaning should be revised according to the parameters of the verification results.
(3) Contamination of materials
Materials are a source of pollution and one of the sources of pollution that we should pay attention to. Materials are the basic part of product composition, especially the raw and auxiliary materials and inner packaging materials that directly contact the product. Therefore, in the key process of the product, we must control the microbial level of the material to avoid contamination of the clean area due to material contamination, which ultimately affects the quality of the product.
Therefore, the materials entering the clean area and the key areas that limit the microbial load are potential sources of microbial contamination. Microorganisms can attach to untreated materials, and it is difficult to make a general threat and risk assessment of these microorganisms. Therefore, supplier audits of materials, zoning management according to material sources, and establishment of microbial monitoring procedures for materials are all commonly used methods to control material contamination.
However, we need to pay more attention to the re-contamination of materials during storage and transfer. Materials entering the clean area must be purified and disinfected on the surface. Before entering the clean area, the route of material purification, disinfection and transfer should be separated from the route of personnel entry to avoid cross-contamination. It is mainly the "sticky dust and bacteria" generated by the conveyor equipment used in the material transfer process and the air pollution caused by the air flow during the transmission process.
If the materials are transported by elevator, people and things should not be combined. The elevator should be located in a non-clean area. If it is located in a clean area, a buffer zone should be set at the elevator entrance.
(4) Air pollution
Air is the carrier of pollution sources in clean areas. Natural air is polluted by microorganisms. Microorganisms attack products by adhering to inactive particles in the air, such as dust particles, water droplets, skin chips, etc., resulting in pollution.
The main way to control microbial contamination in the production of pharmaceutical companies is to use clean rooms, and for more critical processes, isolation technology is also used. Behavior in the clean area must also be carried out effectively according to the specifications. At the same time, other factors affecting the clean area, such as personnel, materials and water, must also be limited.
The air in the clean area is treated by purifying the air conditioning system to ensure that the air in the clean area meets the requirements. Therefore, the prevention and control of air pollution sources should be filtered by Debao air, maintaining positive pressure with the non-clean area, and there should be air lock protection between each level to ensure that the air flows from the room with higher cleanliness level to the lower room.
(5) Water pollution
In theory, microorganisms cannot grow in pure water. However, all types of water, no matter how carefully steamed or filtered, always contain a certain amount of soluble organic matter and salts. It is these soluble substances that microorganisms can use as a source of food for their growth.
In the production process, water is one of the most widely used raw materials. This is why our pharmaceutical factory hygiene procedures must carefully control not only the water used in the production process, but also how to properly clean our equipment with water.
For water pollution control methods, in strict accordance with regulatory requirements, the water used in aseptic filling areas must be filtered aseptically. In low-level auxiliary clean areas serving aseptic drug production areas, pharmaceutical-grade process water should be used, such as purified water and live injection water.
Another very important control measure is to remove the water in the clean area in a timely manner, and disinfect the stagnant area with disinfectant immediately after the removal is completed to minimize the risk of microbial growth.
Overall, to ensure that the microorganisms in the clean area are well controlled, three principles must be grasped: first, to prevent the entry of foreign pollutants; second, to continuously eliminate the pollution; third, to limit the generation of pollution. Control the pollution of active dust and inactive dust.
