Comparison between Chinese pharmaceutical industry standard and European and American Standard of biosafety cabinet

On June 1, 2006, the pharmaceutical industry standard of the people's Republic of China yy0569-2005 was officially implemented, which is the compulsory standard of the pharmaceutical industry on biosafety cabinet issued by the State Food and Drug Administration (SFDA) on July 18, 2005 It is different from the construction industry standard of the biosafety cabinet jg170-2005 prepared by the Ministry of construction and design and yy0569-20 of the pharmaceutical industry 05 standard is prepared by reference to the European standard en12469:2000 of biosafety cabinet issued by Cen and the American nsf49 biosafety cabinet standard recognized by American National Standard Institute (ANSI) Our national yy0569-2005 industry standard actively adopts the important parts of en12469 and nsf49, and improves and modifies the relatively weak parts of these two standards, so that China's yy0569-2005 standard becomes the standard in the field of biosafety cabinets in the world First, in terms of the model of the safety cabinet, yy0569-2005 of China has adopted the same regulations as nsf49-2002 of the United States: to subdivide the secondary safety cabinet First, the three standards have the same regulations on the general classification and performance requirements of the biosafety cabinet: the primary biosafety cabinet only protects the staff and the environment, not the samples The principle of air flow is the same as that of laboratory fume hood The difference is that HEPA (particle air filter) filter is installed at the exhaust port The negative pressure air flow drawn in from the front window operation port protects the safety of personnel, and the exhaust air flow must be filtered by HEPA to protect the environment from pollution Because the first level biosafety cabinet can not protect the products in the cabinet, it has been less used at present The secondary biosafety cabinet is widely used in Zui at present It is a safety cabinet with a front window operation port The operator can operate in the safety cabinet through the front window operation port to protect the personnel, products and environment in the operation process The third level biosafety cabinet is designed for the biosafety level of the fourth level laboratory The cabinet body is completely airtight The staff operate through the gloves connected to the cabinet body, commonly known as glove box The test articles enter and exit the cabinet through the double door transfer box to ensure that they are not polluted It is suitable for high-risk biological tests As for the classification standard of secondary biosafety cabinets, the Chinese yy0569-2005 standard is the same as the American nsf49 standard, which is different from the European en12469 standard: at present, the biosafety cabinets with high utilization rate on the market are secondary, while the European en12469 standard and the Chinese yy0569-2005 standard The nsf49 standard and the nsf49 standard are different: from the basic point of view, the three types of safety cabinets can provide protection for operators, test objects and working environment; the working principle is the same The big difference is that en12469 only has a basic definition of "secondary biosafety cabinet" Like nsf49, yy0569 divides the secondary biosafety cabinet into four types according to the inflow air speed, exhaust mode and circulation mode of the front window operation port: A1 type, A2 type (original B3 type), B1 type and B2 type The airflow velocity of the front window of A1 type safety cabinet is small or the average value of measurement should be less than 0.40m/s (0.38m/s in American Standard) 70% of the gas is recycled through HEPA filter, and 30% of the gas is filtered out through the exhaust port The air flow velocity of front window of type A2 safety cabinet is small or the measured average value should be less than 0.5m/s 70% of the gas is recycled to the working area through HEPA filter, and 30% of the gas is filtered out through the exhaust port This type of safety cabinet is widely used The secondary B-type biosafety cabinets are all safety cabinets connected to the exhaust system of the laboratory The airflow velocity of front window is small or the average value of measurement should be less than 0.5m/s Among them, 70% of the B1 type gas is discharged through the HEPA filter at the exhaust port, and 30% of the gas is recycled through the HEPA filter at the air supply port Type B2 is a 100% full row type safety cabinet, without internal circulation air flow, which can provide biological and chemical safety protection at the same time This type of safety cabinet is also used in a large amount Type 1 and type B1 secondary biosafety cabinets are rarely used in the market at present; type B2 secondary biosafety cabinets are widely used in the field of biological research in China and the United States, but hardly in Europe In the European market, the secondary biosafety cabinet meeting the en12469 is basically equivalent to the A2 type biosafety cabinet of China and the United States (except for some small differences) These two types of biosafety cabinets (A2, B2) are widely used in all kinds of biosafety cabinets in the world at present 2 For the cabinet structure, performance and test of the safety cabinet, the Chinese standard fully absorbs the advantages of the European and American standards, and adopts the strict test standards of Zui For the cabinet structure, en12469 and nsf49 are based on the specification performance, not through the detailed specification requirements to specify how the manufacturer makes the safety cabinet; on the contrary, the manufacturer has great freedom to design its own safety cabinet, as long as it can meet the performance test standards Yy0569 of China clearly specifies the design standard of the cabinet structure of the safety cabinet: the working area of class II A2, B1 and B2 safety cabinet shall adopt the double-layer structure of four sides (left and right sides, rear and bottom) All contaminated parts of the three types of safety cabinets shall be in negative pressure state or surrounded by negative pressure channel and negative pressure ventilation system 2 The three side wall panels in the exposed working area of the class III safety cabinet shall be an integral structure, and the joints on the inner surface shall be sealed, etc It can be seen that the yy0569 standard in China more clearly regulates the cabinet structure design of the safety cabinet compared with the European and American standards, and more conforms to the current biological and chemical experimental requirements 3 Physical performance test and qualification standards yy0569, en12469 and nsf49 all specify the test methods and qualification standards of the safety cabinet The differences and introductions of the three are as follows: 1 Microbial challenge test of personnel, test products and environmental protection In the test of personnel, product, environment and product cross contamination protection project, the test method and qualification standard of the three standards are basically the same, that is, the microbial challenge method is used to test But in the personnel protection test, yy0569 standard in China adopts the same physical test scheme (KI discus test) as en12469 standard in Europe, which is considered to be more convenient and quick based on the conventional microbial challenge test This test method can complete the test results in one minute, which is far less than the time required for cultivation of more than 48 hours by microbiological method, which makes it possible for the manufacturer of the safety cabinet to test each safety cabinet before leaving the factory, and ensures the safety of each ex factory product, which is far better than the manufacturer who uses microbiological challenge method to sample the products 2 Down flow velocity test: the down flow velocity has an important impact on the protection performance of the safety cabinet test sample and cross infection protection performance, for example, too small flow velocity will cause the test sample to lose protection Yy0569 and en12469 both stipulate that the allowable range of downflow velocity of secondary safety cabinet is 0.25-0.5m/s, while nsf49 does not provide any requirements for downflow velocity In the test method of downdraft velocity, yy0569 adopts the method similar to nsf49 (the principle is consistent) Yy0569 and nsf49 both specify multiple test points, which represents higher measurement accuracy requirements Among them, the thermal anemometer used by yy0569, the temperature difference anemometer used by nsf49, and the accuracy and type of measurement instrument are not specified by en12469 At the same time, yy0569 and nsf49 both improve the test accuracy by standardizing the accuracy and model of relevant test instruments, and yy0569 also divides the downdraft of the safety cabinet into two modes of finer uniform and non-uniform downdraft, which is a step higher than the requirements of nsf49 This shows that yy0569 is better than nsf49 in the United States and en12469 in Europe 3 Flow velocity test of inflow airflow: in terms of inflow airflow test, yy0569 adopts the same standard as European standard en12469, and estimates the inflow airflow velocity through the external exhaust flow The American standard adopts the direct inflow airflow velocity test method Although the principle of the two methods is different, the results are the same At the same time, yy0569, en12469 and nsf49 all have regulations on the flow rate of low inflow air Here we compare the requirements of type A2 secondary biosafety cabinet and European "ordinary" secondary biosafety cabinet: yy0569 and nsf49 require 0.5m/s low flow rate of A2 secondary biosafety cabinet, while en12469 requires 0.4m/s low flow rate of A2 secondary biosafety cabinet There are similar test methods for yy0569, nsf49 and en12469 in these aspects, which will not be discussed here 5 Filter integrity test yy0569-2005 and nsf49 both stipulate that aerosol eruption agent (such as DOP, Pao, etc.) is used in filter integrity test; European en12469 standard (using the same test method) uses another test method of natural aerosol (natural air) A large number of studies have shown that the use of natural aerosol test methods can not ensure that all leaks are detected Because the aerosol particles produced by the use of the aerosol generator can easily reach and spread to any specified position in the safety cabinet under the action of the generator pressure, and can make the aerosol evenly distributed in the specified position in the cabinet, especially can completely cover the combination of the filter and the cabinet As for the method of aerosol diffusion in the cabinet by natural air, because the natural air in the cabinet is relatively stable and the mobility and power are poor, the aerosol will not spread evenly to the specified parts in the cabinet, so it is possible that the part where the filter is combined with the cabinet is not completely covered by the air soluble adhesive, which may result in the test results not being available Filter integrity test 6 Cabinet leakage test method yy0569 adopts two standard pressure attenuation methods different from those in Europe and the United States This method uses a pressure gauge or pressure sensor system to display the pressure in the cabinet It can detect the tightness of the cabinet quantitatively, which is very convincing Nsf49 stipulates that the simple soap bubble leakage test is the routine test for all safety cabinets by the manufacturer, and en12469 is the test item of independent certification laboratory, rather than requiring the manufacturer to carry out the test when leaving the factory 7 Other types of tests: in other types of performance tests, the three standards basically adopt the same test methods, such as motor and fan performance test, temperature rise test in the working area, cabinet stability test (including cabinet anti overturning, cabinet anti deformation, worktable anti deformation, cabinet anti forward tipping), etc., which are not described too much here Conclusion although the implementation time and content of the three standards are different, they are similar in general In terms of some key test methods, China's standards not only absorb the methods in European and American standards, but also develop more rigorous test methods Therefore, China's safety cabinet test standard is currently a strict standard in the world It is the basic principle to choose the biosafety cabinet correctly, use and maintain the cabinet correctly according to the operation rules Shanghai Sujing Industrial Co., Ltd