Dynamic monitoring of Class AB clean area of ​​GMP online monitoring system
1. The significance and role of implementing dynamic monitoring In the A/B clean area, the implementation of dynamic monitoring is the necessary basis for personnel behavior evaluation and final product release, so as to find out the problems in time and take effective measures to solve the problems in time to prevent further expansion of adverse effects. At the same time, it provides a basis for further improvement of air balance, personnel behavior and room disinfection methods. In addition, in order to determine whether the clean room has reached the specified cleanliness, and to provide continuous and stable protection for production, it is an effective tool for evaluating the control of the production environment, and is the primary condition for the release of sterile drugs. 2. Dynamic monitoring of projects and standards 2.1 Projects monitored Before the production operation, check and control the temperature, humidity and pressure difference in the area; in the production process, monitor the settled bacteria, floating bacteria, suspended particles and wind speed; after the key operations are completed, monitor the facilities, Surface and personnel hygiene of the equipment. At the same time, the isolation gloves are tested before and after the start of production. 2.2 Temperature and humidity monitoring For example, medium-temperature microorganisms are most suitable for growth at 25 to 30 °C; wet-type microorganisms grow and reproduce in an environment with a humidity of 70% to 90%. Therefore, it is generally necessary to avoid this temperature and humidity range. At the same time, the temperature and humidity are too high or too low, which has a great impact on the comfort of the human body and the working mood of the personnel. It will seriously affect the operation behavior of the personnel in the A/B level area and cannot effectively guarantee the safety of the product. Sex. Under normal circumstances, the temperature of the living environment of the sterile preparation should be controlled at 18 ~ 24 °C, and the humidity should be controlled at 45% ~ 65%. 2.3 Relative differential pressure monitoring The difference of aerostatic pressure between clean areas of different cleanliness levels and between clean areas and non-clean areas should be greater than 10 Pa, and devices with indicated pressure difference should be installed; production areas prone to dust should be adjacent to adjacent rooms (areas) ) Maintain a relative negative pressure; maintain a proper differential pressure gradient between different functional zones (operating rooms) of the same cleanliness level. At present, the commonly used differential pressure gauge range is between 0 and 60 Pa, and the differential pressure differential gauge range is generally selected between -30 and 30 Pa. Therefore, in the daily production process, the calibration or correction of the instrument and the instrument itself should be performed. The situation is strengthened by supervision and management, because the pressure difference can increase the abnormal alarm situation. However, in order to avoid the alarm caused by normal operation (such as opening the door), the alarm delay device can be appropriately increased. The specific delay time can be verified according to the time required for different personnel to open the door, enter or transfer the material, and close the door. 2.4 Particle and microbiological monitoring The design of the clean area must meet the corresponding cleanliness requirements to meet the “static†and “dynamic†standards. At the same time, the area should also dynamically monitor the microbes (floating bacteria, sedimentation bacteria, surface microbes). Microorganisms mainly include viruses, rickettsia, bacteria, fungi and protozoa, and the main related to clean rooms are bacteria and fungi. Bacteria cannot survive alone, so they can block the dust particles through the initial effect, medium efficiency, and (sub) efficient filtration of the air conditioner. At the same time, the bacteria can be blocked. For aseptic areas, microbiological testing is more important, but the period of direct detection is long. Therefore, the particle level can be used to indirectly measure its specific situation. These two aspects of testing can assess the damage and sanitation of the aseptic manufacturing process environment and provide data support for the release of the final product. 3. Methods and points of attention for dynamic monitoring 3.1 suspended particles At present, the methods for determining suspended particles are mainly microscopic method and automatic particle counting method, and the instruments used for monitoring airborne particle monitoring in the clean area are mostly light scattering particle counters and laser particle counters. Based on the actual situation, it is recommended to use a continuous monitoring system to detect airborne particles in the Class A area. The online monitoring system can feedback the monitoring information in real time, so that the monitoring personnel can promptly propose a solution to the problem. For example, the operator is reminded to reduce the range of motion and provide a basis for production process control such as environmental cleaning, disinfection, and shutdown waiting. At the same time, a complete set of operation, testing and replacement procedures should be established for the daily inspection and maintenance of air-conditioning filters. Only by doing so can we effectively control the risks that exist there. 3.2 Floating bacteria The plank sampler is often monitored using a slit sampler in the impact method, and air is drawn through the porous cover while the microorganisms in the gas stream impinge on the surface of the agar medium attached to the standard culture dish. Usually, when measuring the floating bacteria, the sampling amount of each sampling point should not be less than 1m3, and in the production process, the sampler can be set, and the whole process of production can be monitored by the gap method of sampling, waiting and resampling. In addition, the floating bacteria sampler also has sampling methods such as mesh impact type, surface vacuum sampling, centrifugal type, filter type and liquid impact type. 3.3 Settling bacteria The settled bacteria are obtained by collecting the living biological particles falling in the culture dish by the exposure method, culturing them, and then counting them. Petri dishes for sedimentation should be placed in representative locations and where airflow disturbances are minimal. The specific sampling method and culture method is that after placing the culture dish at a position close to the operation height, the outer cover is opened and the buckle is placed to expose the surface of the medium. In the static monitoring, the culture dish should be placed for not less than 30 minutes before the cover is collected. In the dynamic monitoring, the exposure time should be verified according to the sedimentation disc itself and the environment. The exposure time of the single sedimentation disc can be less. At 4h, but not more than 4h. In the same position, multiple sedimentation discs can be used to continuously monitor and accumulate counts, and then collect. Yeasts and molds are usually counted after incubation for 5-7 days at 20-25 °C, while aerobic bacteria are usually at 30-35 °C. The cells were cultured for 48 to 72 hours and counted. The sedimentation disc is widely used in the environmental detection of clean areas because of its advantages of low cost, light weight and less damage to the air environment. However, when using a sedimentation disc, the exposure time of the sedimentation disc should be confirmed (remember the opening and ending time of the plate) to ensure that the exposed medium does not affect the normal growth of microorganisms due to water loss and the like. At present, many manufacturers of petri dishes are self-contained by the factory, and the culture vessels that are not sealed are not strong. In the production process, the transport will cause pollution to the petri dish itself, and the results will be false positive. Therefore, it is recommended that in the production process, the blank of the petri dish itself should be used or a petri dish with good sealing should be purchased to improve the credibility of the test results. 3.4 Surface microbial testing Surface microbiological testing of objects can determine the degree of contamination of surfaces on objects (including work clothes). Under normal circumstances, you can use the cotton swab indirect sampling, culture, direct contact sampling and surface washing methods. When using the direct contact method, the contact disc used should be placed at room temperature and used. 3.4.1 Cotton swab wiping surface sampling method The sampling area of ​​the cotton swab wiping surface sampling method is generally 25 cm2, and the human body surface wiping should at least include the fingerprints of the hands, the head, the mask, the shoulders, the forearms, the wrists and the legs. The indirect sampling of the cotton swab is suitable for irregular surfaces. When sampling, hold the swab handle with the hand and contact the sampling surface at an angle of 30°. Use S-type or Z-type slow and swollen cotton swab to fully wipe. If the swab head is a calcium alginate material, use a dilute hydrochloric acid solution as a diluent (such as a 1% sodium citrate solution) to allow the swab head to dissolve completely. 3.4.2 Direct contact method The direct contact method is to directly contact the surface of the object to be sampled by the contact dish. The contact time is generally about 10s, and the colony will grow after the cultivation. This method is widely used because it is easy to handle and can be quantified. However, this test is only suitable for flat, smooth surfaces and is usually sampled before clearing or filling. After sampling, the surface to be sampled is wiped with a gauze containing 75% by mass of ethanol to remove the residue. The sampled dish after sampling and placed in the incubator is placed in an incubator for cultivation. The parameters of the incubator are generally set at 30 to 35 ° C, and counted after 72 hours of culture. 3.4.3 Surface rinse method The surface rinsing method is suitable for monitoring the microbial bacteria content on the inner surface of a large area, including equipment tracks, water storage tanks, and the like. Rinse the surface with a volume of sterile water, collect the rinse water, and calculate the number of microorganisms by membrane filtration. 3.5 Wind speed test Detect the wind speed in the A-class zone during the production process, so that the wind speed of the production environment meets the guiding value (0.36~0.54 m/s). At the same time, it can also judge whether the laminar flow is open, whether it is running normally, whether it is blocked or leaked, and the production environment Meet the requirements. At present, since the installed isolator has good airtightness, the laminar wind speed can be appropriately reduced by corresponding verification. Some literatures indicate that the A-zone can choose the flow pattern of positive pressure sterile turbulence, and it is not necessary to choose the laminar flow pattern. 3.6 Detection of isolation operator gloves At present, the integrity test is generally used when testing gloves, and a certain pressure is applied to the inside of the glove. Within a specified time, the pressure drop value is regarded as acceptable within the acceptable range. In addition, it is also possible to increase the visual inspection procedure of the gloves before and after the production of each shift. The inspection cycle should be verified based on factors such as product characteristics, equipment and shift schedule. 4, daily monitoring of sampling points and sampling frequency The location of the most critical point as a sampling point does not necessarily apply, so the probability that environmental monitoring will increase the risk of product contamination must be considered. For example, the sampling point of suspended particles is generally placed at a position of 0.8 to 1.5 m from the ground. Try to avoid sampling near the return air inlet, and the tester should stand on the downwind side of the sampling port. The sampling points and sampling quantities in the clean area monitoring can be less than the sampling points and sampling quantities when the clean area level is confirmed. The sampling points are verified by verification, and they are analyzed by risk analysis and monitoring results (at least 6 months or more) The operational data is used as the basis for the analysis). The frequency of monitoring is also a subject worth pondering. If the frequency of monitoring is insufficient, it will not reflect the problems that exist in it. The frequency of monitoring is too high, which is not conducive to resource optimization. Therefore, the determination of the frequency of monitoring generally uses the risk value distribution (RNR), which is the product of the severity of the occurrence of the risk (SEV) and the probability of occurrence of the risk (OCC). Different monitoring frequencies are determined according to the magnitude of the risk value, and practical measures are also taken to reduce the risks. 5, the general over standard processing method and report printing In the daily monitoring process, if the monitoring data is biased, the data will be higher than the set limit. Therefore, it is necessary to investigate what happened through the CAPA (prevention and corrective measures), how to prevent the problem from happening again, and the deviation and The follow-up measures must be recorded accordingly. Therefore, we must analyze problems from the six aspects of people, machines, materials, methods, loops, and surveys, use risk assessment tools to check risk points, find out the causes, and formulate practical measures to solve problems. At the same time, we can also do the necessary training. , assessment and assessment work in order to solve the problem fundamentally. During the daily monitoring process, each batch of reports is printed and attached to the production records of the corresponding batch. Production time can generally be divided into preparation, self-purification, production and clearance stages. However, the time of report printing should include the self-cleaning time and production time of the environment, and the remarks should be explained to explain the monitoring of abnormal and excessive results, so as to ensure traceability of product production. Sex. 6 Conclusion With the increase of drug supervision and the increasing market requirements, pharmaceutical manufacturers must strictly control the whole process of production, especially the whole process of production of sterile drugs. The application of automation technology makes the unmanned operation of the pharmaceutical production line gradually become possible; the use of sterile isolators makes it possible to operate unmanned key processes. However, at present, there are still some shortcomings in the use of domestic isolation operators. For example, online monitoring of the process of placing and removing culture dishes, difficulty in performing online replacement of gloves, and lack of emergency treatment measures when there is a leak in the system. In response to these problems, more systematic research is needed. At the same time, the application dynamic monitoring system can provide data and alarm information in real time, facilitate the timely control of the production process, and take effective measures to solve the problems in the production process. In addition, the application of online monitoring system can reduce the pollution caused by the production environment and ensure the quality of the product.
Penis enlargement can be achieved with a minimally invasive injection of Dermal Fillers. Injections can increase the girth of the penis while also increasing the length of the flaccid penis. Using hyaluronic acid fillers for injection is preferred Penis enlargement can be achieved with a minimally invasive injection of dermal fillers. Injections can increase the girth of the penis while also increasing the length of the flaccid penis. Using fillers for injection is preferred.
Rimless Industry Co., Ltd. (RIMLESS) is devoted to the global brand operating and integrating, sale and after-sale services of biomedical materials, high-end medical devices, regenerative aesthetic products,cosmetics and beauty tools.
Fillers For Penis Enlargement,Dermal Filler Penis Enlargement,Penile Injectable Fillers,Penile Enlargement Dermal Fillers Rimless Industry Co.,Ltd. , https://www.rebornplla.com
RIMLESS is the exclusive distributor, exporter and global brand licensor of REBORN. We take REBORN and RIMLESS as the core brands, biomedical materials and their applications in the medical field as the main business, and the high-end medical devices as the research and development direction.
We have exported over 50 countries and areas in the world and won a very good reputation and long-term partnership with our customers.