The application of aseptic operation technology in the production of sterile preparations1
Abstract Purpose: With the development and progress of the society, the medical level is also progressing, and the technology is also constantly updated.
About sterile preparations in the modern society is also more and more common, therefore, the production of sterile preparations in the stage of medical development has a very important position.
This paper combines the development status of the production of aseptic preparations at home and abroad, as well as the update of aseptic operation technology and research results, from the basic overview of aseptic preparations, aseptic operation technology is commonly used in the basic technology, such as isolation technology, information engineering technology, and so on, and at the same time, combined with the application of aseptic operation technology in the production of aseptic preparations in the actual situation of the current stage of the research briefly explored.
Keywords aseptic preparation; production; operation technology; isolation technology; information engineering
1 Introduction
Due to the rapid development of social and economic development, the western level of medical care has an extremely important impact on the reform and development of medicine in China.
The development of aseptic operation techniques in sterile preparations is even more rapid today.
With the improvement of people's living standard, the pursuit of high quality of life has put forward corresponding requirements for the development of modern social medicine.
For the production of aseptic preparation which is closely related to the patients, it is not to be neglected, and it is not difficult to conclude that the importance of aseptic operation is self-evident.
2 Analysis of the current situation of the production of aseptic preparations
On the aseptic, refers to any designated object, medium or environment, there shall not be any live microorganisms; aseptic preparation refers to the use of aseptic methods or techniques prepared without any live microbial propagation and spores of a class of pharmaceutical preparations, it can also be said that the aseptic preparation refers to the legal standards of medicines with aseptic inspection items. The preparation, including small and large volume injections, can also be said to be aseptic preparations that have a sterility check listed in the legal drug standards.
According to the production process can be divided into two categories: the final sterilization process for the final sterilized products; part or all of the process using sterile production process for non-final sterilized products.
At present, the domestic and international uniform recognition of the need to do aseptic testing of a wide range of pharmaceutical preparations, can be roughly summarized as eleven.
Mainly: all the injections; intraocular injection solution, intraocular implants and for surgery, wounds, corneal penetration injuries with ophthalmic preparations; for burns or severe trauma ointments, creams; implants; for burns, wounds or ulcers, aerosols; for burns, wounds or ulcers, sprays; for burns or traumas, topical dispersions; for surgery, ear wounds, or eardrum perforation. ear drops and ear washes for surgical wounds; nasal preparations for surgical wounds; douches; gels for severe wounds.
3 Aseptic operation and aseptic operation technology analysis
Aseptic operation refers to the use or control of certain conditions throughout the operation, so that the product to avoid microbial contamination of an operation or technology.
For the current widely used aseptic operation of the main purpose is used to prevent microorganisms from entering human tissue, on the other hand, can be more broadly understood as other sterile range of operating techniques called aseptic operation, such as surgery to prevent bacteria from entering the wound.
Aseptic operation is not only used in medical treatment, but also in a wide range of biological experiments, the purpose of which is to prevent the growth and reproduction of microorganisms affecting the experiment, and therefore also in a sterile environment.
In the process of aseptic operation, the most important thing is to keep the work area sterile and clean, so 20 to 30 minutes before the operation to start the ultra-clean table and ultraviolet lamp, and carefully wash your hands and disinfection.
During operation, it is strictly prohibited to make noise, and it is strictly prohibited to take sterile items, such as bottle stoppers, etc., directly by hand, but must use sterilized hemostatic forceps, tweezers, and so on.
Culture bottles should be operated in the ultra-clean table, and need to be repeatedly burned with an alcohol lamp when opening and capping the bottle.
Pipettes should be held in the back 1/3 of the hand, with a rubber nipple, and grilled with an alcohol lamp before pipetting.
What may seem like a brief detail is actually critical in aseptic operation.
4 The development and application of aseptic operation technology analysis
Aseptic operation technology is extremely widely used, both in the field of biology, and medical and pharmaceutical aspects, play an irreplaceable role.
In the field of actual production, the human being, as the operator of the technology, is the greatest danger in the process of aseptic operation.
The incomplete asepsis of the human body poses an extremely serious challenge to aseptic operation in the production of sterile preparations, so one of the key points of technological renewal and advancement is to overcome the obstacles at this stage.
Isolation technology uses a physical barrier to isolate the controlled space from the external environment, a kind of absolute isolation.
Isolators, which are primarily used in sterile pharmaceutical manufacturing, utilize renewable and effective means of decontamination, sealed or exchanged through high efficiency particulate air (HEPA) filters, to prevent microbes from entering the surrounding environment and contaminants from personnel from entering the controlled environment.
The system allows material to enter and/or exit through designed and validated pathways and excludes the entry of contaminants.
Isolators are primarily used for aseptic processing or sterile testing.
Modern isolators tend to use stainless steel frames to support windows, gloves, transfer stations qualified ventilation and air conditioning systems, and high efficiency filters.
The airflow is propelled like a piston from the top down and is pumped out through the isolator floor.
The widespread use of isolation technology can meet the need for improved product quality, improved safety and security requirements, while reducing operating costs and providing a special environment, isolation technology makes aseptic operations a? Mobile aseptic chambers?
5 The use of information engineering technology in the production of sterile preparations
The promulgation of the new version of GMP, the Good Manufacturing Practice, has a guiding role in the field of sterile preparation production.
And the new version of the Good Manufacturing Practice for the production of sterile preparations in the use of information engineering technology put forward new requirements, that is, the production of sterile preparations can be through the air conditioning automatic control system, sterilization equipment data acquisition system, suspended particles on-line monitoring and other information engineering technology to debug and integration of the production of aseptic preparations.
The air conditioning system is the most critical control point in the production of sterile preparations, which plays an important role in the quality of drugs.
Sterilization equipment is the key link in the production of aseptic preparations, is the premise of drug sterility, and the means of controlling sterility is to control the temperature, high temperature sterilization.
On the other hand, the application of data acquisition systems in sterile preparations is more common.
Information engineering has a wide range of applications in the production of aseptic preparations with its unique advantages of accuracy, efficiency and automation.
Information engineering technology is applicable to the production of aseptic preparations, so that the quality of aseptic preparation products are guaranteed, but also at this stage of China's production of aseptic preparations to achieve higher requirements.
6 Conclusion
Aseptic preparation production is of great significance to the modern pharmaceutical and biological fields, and the input and extensive use of aseptic preparations have undoubtedly had a far-reaching impact on the modern pharmaceutical industry, especially the core production process of aseptic injections.
The application of aseptic operation technology in the production of aseptic preparations is more to ensure the safety of drugs, operators and end-users of drugs safety is necessary to ensure that we must continue to increase the production of aseptic preparations and aseptic operation technology in a timely manner to update, to maintain the advanced nature of its field, and at the same time, the production of a more qualified products, reducing the production process may be a problem.
This is not only a requirement for the field of aseptic production, but also a commitment to the safety of operators and end users of medicines.
References
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Application of Aseptic Operation Techniques in the Production of Aseptic Preparations2
Keywords: aseptic operation; technique; application
Aseptic operation The operation technique used to prevent microorganisms from entering into the human body's tissues or other sterile ranges is called aseptic operation.
Aseptic preparations are preparations for which a sterility check is listed in the legal drug standards.
Aseptic preparations can be divided into two categories according to the production process: final sterilized products using the final sterilization process; and non-final sterilized products using aseptic production processes in some or all processes.
In this paper, the application of aseptic operation techniques in the production of sterile preparations is summarized.
1 advocate the clean room in accordance with the principles of aseptic operation
1.1 The amount of bacteria
The amount of dust in the clean room, products, materials, etc., in the process of transportation of dust and human hair compared to the amount of dust, generally negligible; hair dust is mainly from the people, accounting for about 90%.
The amount of dust generated during the action generally reaches 3-7 times the rest time.
Pollution generated by the staff: humans shed about 1000 pieces of skin per minute (average size of 30 * 60 * 3 microns); human hair has been shedding; human walking at a speed of 0.9m / s will produce 5000000 particles per minute greater than 0.3 microns; human stationary and sitting and standing will produce 10,000 particles per minute greater than 0.3 microns. Humans moving their heads and torsos generate 1,000,000 particles larger than 0.3 microns per minute.
Clean room when the staff wear sterile clothing: walking fast when the amount of bacteria for 900-2500 / min. people; static amount of bacteria is generally 10-300 / min. people; body general activities when the amount of bacteria for 150-1000 / min. people; no mask amount of bacteria: the amount of bacteria with a mask 1:7 ~ 1:14; wearing the usual clothing The amount of bacteria is 3300～62000/ min.
The general provisions of the clean room sterile clothing personnel static germs generally not more than 300 / min.
1.2 Relevant regulations
"Drug Production Quality Management Code" 2010 Revision: Article 33, visitors and untrained personnel are not allowed to enter the production area and the quality control area, special circumstances do need to enter, should be guided in advance on personal hygiene, changing clothes and other matters.
Article 20, the number of people in the clean area should be strictly controlled, inspection and supervision should be carried out as far as possible outside the clean area of sterile production.
Article 37, the operator should avoid direct contact with bare hands on the surface of drugs, packaging materials and equipment in direct contact with drugs.
Article 24, changing clothes and hand washing must follow the appropriate written procedures to minimize contamination of the clean area or bring contaminants into the clean area.
Article 37, operators should avoid direct contact with drugs, packaging materials in direct contact with drugs and equipment surfaces with bare hands.
Article 24, changing clothes and washing hands must follow the appropriate written procedures to minimize the contamination of the clean area or bring contaminants into the clean area.
2 Violations of aseptic practices in the manufacture of sterile medicinal products
Littering of used gloves, opening doors without sterilizing gloved hands, squeezing of work clothes, running, shouting unless really necessary, inverting sterilized vials of syringes with the arm stretched out over open vials of syringes, touching of gloved hands to surfaces and materials, entering the clean room with a cold or during other illnesses, wearing of jewelry and watches in clean rooms, and the use of gloved hands to touch surfaces and materials. Wearing jewelry and watches in the cleanroom, sliding objects on the bench, leaning on surfaces, communicating through holes, entrances, exits, or air locks, sneezing, and touching the floor.
3 Cause analysis
Poor aseptic awareness.
Asepsis training is mostly microbiology to aseptic operation less.
In the event of minor equipment failure, the operator will do some abnormal operation actions, violation of aseptic operation occurs from time to time.
4 Solutions
Repeatedly carry out training on the concept of asepsis, and according to the actual production, develop detailed aseptic operation procedures.
The changing of aseptic operators can be a very high risk of microbial contamination, and human contaminants are likely to contaminate sterile gowns during the changing process.
Therefore, it is important to have two sets of sterile gowns, with the outer sterile gown requiring strict changing in a sterile changing room and ensuring no human contamination.
The sterile room must be limited to the number of people entering.
The maximum number of people should be determined by verifying that there is no impact on the indicators of a sterile environment.
All behavioral practices of cleanroom personnel must be consistent with the principles of aseptic operation, and no practices should affect product sterility.
Non-production personnel are likely to bring microbial contamination to the sterile production area during the changing process, as well as during the operation of the sterile production area.
Therefore, access to the aseptic production area by non-production personnel should be strictly controlled, and if access is required, it should be carefully trained and supervised by aseptic production area personnel.
The normal operation of the equipment is very critical to ensure that the normal operation of the equipment, is the operator to reduce abnormal operation. The main guarantee.
5 Discussion
The special nature of sterile drugs determines the high risk of its production process, how to control the quality risk, is the problem that sterile drug manufacturers must face.
It is necessary to strengthen the concept of asepsis of the operators and supervise the aseptic operation of the operators, and to establish a mechanism linking the interests of the operators and the quality of the products is an effective way to guarantee the sterility of sterile drugs.
As it is impossible to do everything in the operating procedures, it is necessary to establish a code of good behavior.
Critical areas of good behavior requirements should include: minimize the number of people entering the clean area and the number of times; only use sterile instruments to contact sterile materials; personnel in the sterile area before entering the application of sterile disinfectant (such as alcohol) to disinfect hands, to be disinfectant evaporation dry before entering the sterile area; each time after contact with the goods should be disinfected hands, drying for the next step in the operation; into the critical area should regularly check the dress code, and the next step in the operation. The dress code should be checked regularly after entering the critical area; the dress code requires the correct size of clean clothes, wearing unbroken clean clothes, no nail polish, no make-up, no jewelry, no confusion about the category of clean clothes, no watches.
From the point of view of reducing the risk of microbial contamination, it is recommended that gloves and masks be worn after the inner layer of sterile clothing is put on, and then the outer layer of sterile clothing is put on.
Posture requirements: keep the body away from the product, do not squeeze the coveralls, do not lean on surfaces, stand up straight to minimize disruptive airflow, and keep arms at or above the waistline.
Action requirements: avoid unnecessary movements, when not involved in the process operating room, smooth, accurate, smooth movements, can not run, the operator should stand or sit.
Behavioral requirements: can not touch the floor.
When there is an item falling, it can be removed during clearing if it does not create a risk, hands should not touch the floor at any time in the critical area, etc.
Speech requirements: no communication through holes, entrances, exits or airlocks, no unnecessary talking, no shouting unless really needed.
References
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3
Abstract In the current drug making and production work, sterile drug production is one of the most demanding and risky pharmaceutical projects.
In the current development of society, the latest publication of drug control for aseptic production of the most changes and requirements, but also put forward a new view and understanding of the standards, so that the production of drugs control and product quality assurance basis.
This paper analyzes the various aspects of aseptic control in the production of aseptic drugs, and proposes related work and control points.
Keywords aseptic drugs; production; pharmaceutical
Drug production control and output quality has a better guarantee, China's pharmaceutical companies are facing a new round of challenges to improve the level of aseptic control; however, many pharmaceutical companies in order to pass the certification, had to invest heavily in the transformation of the environment, and production equipment upgrades.
But only the hardware update is not enough, how to correctly understand? The quality comes from the design?
First, the aseptic drugs overview
Since the new century, with the increasing number of aseptic drugs, the relevant enterprises and units in the work of the production of aseptic drugs to ensure that the production of aseptic drugs gradually put forward a new standard and understanding, while in the process of the work of the overall aseptic to ensure that the ability to continue to improve the level of control, so as to solve the production of aseptic drugs there are a variety of operational risks and details of the issue of effective control of their production quality and efficiency. The control of its production quality and efficiency, so as to achieve the real realization of the production requirements of sterile drugs.
1, the concept of aseptic drugs
Aseptic drugs refer to the preparations and raw materials listed in the statutory drug standards for aseptic inspection items, including sterile preparations and sterile raw materials.
2. Key points of sterile drugs
The production of sterile drugs must meet the requirements of their quality and intended use, and should minimize microbial, particulate and pyrogenic contamination.
The skills, training and attitude of the production personnel are key factors in achieving these objectives. The production of aseptic drugs must be carried out in strict accordance with well-designed and validated methods and procedures, and the sterility or other quality characteristics of the product should never be dependent solely on any form of final processing or finished product testing (including sterility testing).
II. Assurance studies of sterile drug production
Sterile drug production has received the most attention in the current pharmaceutical field, and is one of the most critical and valued parts and modes of work in the current pharmaceutical field.
In the development of modern society, the production of aseptic drugs for the production of equipment, staff and materials in the production of relevant sterilization measures and methods need to be used to kill and eliminate a variety of microorganisms and germs, so as to ensure the quality of aseptic drug production, sustainable, for the development of the whole society to provide a good foundation platform, and at the same time effectively guarantee the quality of drug production and efficacy requirements.
1, the principle of production
In the production of drugs, its ultimate goal is to provide high quality and efficient drug system for human life and health, thus forming a comprehensive and perfect pharmaceutical system.
Therefore, in the current pharmaceutical production, we need to meet the use and intended function of its requirements, as far as possible to reduce which also contains a variety of microbial elements, so that a variety of particles and pollutants can be controlled and processed, so as to make the formation of a sterile or no other contamination of a mode of work and work system, but also in the production of the most worthy of our attention and attention. It is also one of the most worthy of our attention and attention in the current production.
Aseptic drugs, especially infusion, injection in the production process because of its own is a high-risk products, so for the clean zone staff, working environment, and a variety of equipment and devices need to be strictly controlled, and in a variety of materials before entering the early treatment and disinfection, in the process of production of the most basic principle is to prevent the production and emergence of a variety of contaminants, especially the relevant staff or the relevant personnel or the work environment, and the work system is also the most worthy of our attention and attention. The most basic principle in the production process is to prevent a variety of sources of contamination from arising and appearing, especially the relevant personnel or materials, but also to strictly control the establishment of a strict post control theory and control system, so that the aseptic pharmaceuticals can meet the expected standards and requirements.
2, production process classification
In the current production of aseptic drugs, the production process in accordance with the current equipment and use of analysis can be divided into two categories, the first of which is mainly the use of the final sterilization process to form the final sterilized products, but also the final formation of a sterilized drug in the work; part of the drug in the process of production is based on the aseptic production of production measures and methods. way.
3, production control points
3.1 follow the national requirements
In the current latest GMP regulations and implementation of the basis to ensure that the use of sterile medicines safety, efficacy and stability to become a focus of attention, but also in the work of the work must be managed from the production of a focus on a mode of work, and at the same time need to be firmly grasped in our work! There is a law must be followed, according to the rules and regulations and evidence-based work mode, the application of such production measures and processes for the realization of aseptic drug production quality is very critical and attention to the entire pharmaceutical engineering to grasp the milk brother of the most people's attention and attention to a part of the.
In the current pharmaceutical production work, to achieve the corresponding law, law enforcement is very critical and important links, and in the process of applying the provisions of the production process is through the product design, quality standards, production, technology, and management measures and other aspects of the process of summarizing and dealing with the process, which is the management of one of the most critical and important content and links, and is also the basis for production control. At the same time, it is also the basis for the realization of production control.
3.2 Production process standardization requirements
In the current pharmaceutical production work, whether the newly promulgated GMP or traditional management standards, the production and packaging of drugs put forward a clear management control requirements and the basis of the basis, which is the entire production of pharmaceutical work in the main legal basis and the basis of the rule of law.
In the production of sterile drugs, the so-called drug production is mainly worthwhile in the production of a certain number of provisions or the need for raw materials and packaging materials need to indicate the various precautions and production processes, and after approval of its shall not be arbitrarily changed.
The production process is a guiding document of the production process, which is the basis for the preparation of the post operating law and the development of post production record forms.
The post operation law will be process regulations in the process conditions further refined and specific, so that the production operation procedures are more clear, that is, the process regulations on the production process is a guiding document, and the operation law is to achieve the process requirements of how to implement the specific methods and steps.
Process regulations are the core of production management, is the chapter and the law, is the basis for production, is the embodiment of the GMP guiding ideology; and the operation of the law is how to implement the process regulations of the methods and measures, is the practice of doing things by the rules of the steps and procedures.
Production records are the implementation of procedures, operating parameters, the implementation of the results of the text and data records, is an important file can be found.
The three of them constitute the whole process of production management.
4, operating technology
4.1 personnel operation
The personnel engaged in aseptic operation and enter the other personnel must be strictly selected, and after the training and assessment of the qualified, before they can go on duty operation.
4.2 Time requirements
Microorganisms are ubiquitous and dynamic growth, geometric fission reproduction.
Therefore time limits are necessary to control microbial populations.
Water for injection is used within 24 hours, sterilized supplies and utensils are used within 48 hours, and the waste in the clean area must not accumulate and exit in time to reduce contamination.
Third, conclusion
Asepsis check is not and can not take a batch of products 100% check, so that the batch containing a small amount of microbial contamination of the product is also likely to pass the aseptic check.
There are obvious limitations to sterility testing.
Aseptic test results provide only a suggestive reference, and the assurance of sterility of a sterile product must rely on strict control and verification of production operations, advanced production equipment, and a rational process.
With the development of science, our sterile products will be perfected day by day.