Discussion on the implementation of GMP in pharmaceutical machinery

China Pharmaceutical Equipment Industry Association clearly regards the implementation of GMP for pharmaceutical machinery as the main task of industry management, which is proposed by analyzing the development of pharmaceutical machinery in China, aiming to further highlight the characteristics of pharmaceutical machinery products and improve the design and innovation level of domestic pharmaceutical equipment At present, although the scale, variety and output of pharmaceutical machinery production have considerable strength and level, and become a larger professional product industry in China, with the integration of economic and trade with the world and the internationalization of GMP norms, pharmaceutical manufacturers have an urgent demand for the GMP concept of pharmaceutical equipment and more perfect functions, which makes the GMP of equipment increasingly become one of the domestic and foreign trade Hot spots of technology and competition According to the recent pharmaceutical machinery exhibition, the number of manufacturers has increased year by year, the number of similar products and the number of new products have decreased, and the competition of many similar products in the same region tends to be obvious (such as: Nanjing hot air circulation oven, Jiangsu and Zhejiang rotary vibrating screen, etc.) It should be said that in the previous years, the pharmaceutical machinery has been pursuing the development of vibration on the scale of varieties, and now it should be pursuing the development of competition on the level of quality The implementation of GMP in pharmaceutical machinery is another development opportunity after the implementation of GMP by pharmaceutical enterprises in the 1980s, the elimination of 1cr18ni8ti by the state, the widespread use of low-carbon stainless steel in raw materials of pharmaceutical machinery, the introduction of foreign advanced technology, the emergence of new products and the active adoption of international standards to improve the quality of pharmaceutical machinery products It is also the production opportunity of the "Eight Power coalition" in pharmaceutical equipment industry The product is innovated and improved under the GMP standard to create a development space for further improvement of the function of the drug delivery machine The article refers to "equipment GMP", which is explained as follows: equipment GMP is an important part of the pharmaceutical production management system, which represents the efforts of pharmaceutical equipment to implement GMP itself, and can also be used as a special term in the implementation of GMP in the industry The following article discusses the GMP key points of pharmaceutical equipment based on the relevant requirements and understanding of the specification, which is only for reference 1、 General situation of GMP specification and proposal of equipment GMP GMP originated from FDA of the United States Its guiding ideology lies in the control and management of the whole process of drug production, so as to achieve the "safe" and "effective" drugs After the implementation, GMP has produced good social effects, and it has been quickly used for reference by who and other countries, regions and pharmaceutical enterprises GMP internationalization trend has emerged, such as Switzerland, Britain, Japan, Germany, China and dozens of other countries GMP laws and regulations have been issued one after another, or illegal laws and regulations, but no matter what attribute of GMP, they are very comprehensive and strict, so far in the pharmaceutical industry, they are very strong and binding In terms of the scope of GMP control, it involves a wide range of aspects, including personnel, plant, equipment, facilities, production process, transfer, analysis, verification and warehouse management, which shows that GMP is a systematic specification, and its management details are no less than TQC Although they have many similarities, GMP is a regulation in nature, TQC is the difference of activities, and strictness is the prominent feature of GMP Pharmaceutical equipment is not only an important means of production, but also one of the pollution factors that can not be ignored This is the consistent view of GMP on pharmaceutical equipment GMP, cGMP (API) of who and FDA and the current GMP texts of China all take the equipment as independent chapters Although there are not many discussions, they cover the design, manufacturing, installation, maintenance, use, etc for example, the requirement of "overall cleaning" can be understood as the external and internal parts of the equipment, but also a group of equipment, with strong principle For this personal understanding, GMP is mainly put forward from the perspective of drug administration management and use, so it is mostly considered to be the requirements for equipment use In addition, there are industry separation factors between drug production and equipment manufacturing, and due to the lack of details of equipment implementation, equipment manufacturing has always been in the call for requirements, but failed to form a main dynamic situation From the analysis of the relationship between pharmaceutical equipment and pharmaceutical production, pharmaceutical equipment not only relates to the modernization of pharmaceutical industry, but also has a great impact on pharmaceutical production in terms of equipment specifications, structure, materials and performance For example, if the equipment specifications are not matched with production, a batch of "paper batch" composed of multiple output will be produced for the production of API, resulting in the absence of drug mixing degree For example, the manual, semi-automatic and single function equipment can not make the pharmaceutical process continuous and limit the scale and modernization of the pharmaceutical industry These problems confirm the close relationship between the equipment and GMP According to industry data: strictly speaking, there are not many pharmaceutical products that can truly meet GMP standards Compared with system and management software, hardware seems to be more important for factory facilities and equipment From the perspective of international GMP trends, in the future, pharmaceutical special equipment, sealing devices, blocking facilities, automation and computer processing will enter GMP as new contents, and Japan has developed "GMP for medical devices" Therefore, the issue of specifying the GMP content of pharmaceutical equipment arises, which will make it easier to operate It is exactly the intention of the industry to engage in the GMP of equipment With the enhancement of GMP awareness, pharmaceutical manufacturers are more cautious in the selection of equipment, with full function prior to single function, innovative prior to old products, simple appearance prior to non packaging They think that the price does not represent the performance and quality of the product, the price is always considered after Zui, and the loss of poor performance (energy consumption, pollution, etc.) is long-term, which may be far greater than the investment in equipment What kind of equipment can be regarded as the implementation of GMP, which can not be judged accurately only by the current GMP In accordance with the specification, the equipment GMP is preliminarily defined as: it has the process function, health, safety and other supporting functions required for drug (drug) production, equipment structure and materials used, does not nest, retain materials, does not pollute the processed materials, and does not produce any environment other than production Equipment that is contaminated or affected and easy to operate, maintain and clean This is just a conclusion With this preliminary definition, design can be promoted and GMP essentials can be permeated into product manufacturing 2、 To carry out the analysis of the key points of GMP for pharmaceutical equipment, combined with the definition of GMP for equipment, then all pharmaceutical machinery products can generate their own GMP control scope and GMP innovation concept space The complexity of pharmaceutical technology determines the diversification of equipment functions, and the advantages and disadvantages of the equipment are mainly reflected in whether it can meet the use and environmental applicability Therefore, the applicability requirements of pharmaceutical equipment under the specific conditions of pharmaceutical GMP are more than that of ordinary mechanical products The following requirements for applicability are briefly described from several aspects: 1 The design and required functions of the functions refer to the mechanical and electrical movement functions of the pharmaceutical machinery to complete the basic process actions under the specific use and environmental conditions, and the auxiliary functions such as making the medicine and the workshop area not polluted during the operation With the development of high and new technology, the penetration of new technology in cross fields, the application of advanced principles, mechanisms, control methods and detection means, the functions of pharmaceutical machinery are constantly enriched and improved However, the requirements of pharmaceutical production for equipment are becoming more and more stringent The conventional design has not met the requirements of cleanness, cleaning and non pollution in pharmaceutical industry Therefore, it is necessary to consider improving or increasing pharmaceutical production Functions required for production Only the main functions related to GMP are discussed below (1) Purification function Cleanliness is one of the key points of GMP For the equipment, it has two meanings: the equipment itself does not pollute the production environment and does not pollute the drugs In order to reach this standard, it is necessary to design a purification function on the equipment in principle for any drug (drug) exposed, room area generally not clean or possible man-machine pollution The functional form required by the equipment in different occasions is also different For example, for the equipment with hot air circulation drying, the air pollution is obvious, and the air purification; the cleanliness of water used for bottle washing and water injection machine; the control of dust dispersion for powder machinery such as crushing, pelletizing, coating and tablet pressing; the dust-proof problems of filling equipment need to be solved by other purification methods and devices In order to prevent accidental pollution, FDA suggested in cGMP that we should consider as much as possible that the equipment should be implemented in a closed system, i.e "no sunlight" device Of course, this is not easy to achieve, but it is not impossible Like a one-step granulator, the original multiple equipment and open production processes are combined in a closed internal circulation container equipment to complete, creating a precedent of combination of pharmaceutical principles and purification requirements There are many aspects of purification, such as: water, gas, dust, etc the design of a multi-functional extraction tank adopts computer program control to make the whole process of feeding and discharging automatically, so as to achieve the separation of man and machine in operation and production In addition, it also has the function of automatic extrusion and slag discharge (waste slag can be burned and used), which has a distinctive innovation and shows a strong competitive momentum in many similar products Therefore, as long as the equipment design can meet the above points and is reasonable and feasible, the equipment has this function (2) Cleaning function At present, the equipment cleaning is mostly in manual cleaning, and there are not many in-situ cleaning While manual cleaning overcomes the cross contamination between materials, it is often easy to bring new pollution In addition, the equipment structure factors make it difficult to clean, and so on Such cases are more reflected in the production With the emphasis on the purity and effectiveness of drugs, the CIP function advocated by GMP will become the development of cleaning technology There are also some CIP reports in China, such as the self-cleaning device designed for the rotary seal of the vacuum exhaust pipe and the tank body of a double cone dryer, the high-pressure water flushing mechanism designed for a large liquid container, and the improvement of the mirror of a fermentation equipment into an easy cleaning structure For cleaning, in the past, manufacturers did not necessarily understand the cleaning requirements of material change and batch change in the use of equipment, often either ignoring the design of this function or unconsciously increasing the difficulty of equipment cleaning For example, the coil structure of material liquid heating container is not easy to clean, but also increasing the possibility of bacteria contamination In some pure water transmission systems that do not think there will be pollution, from its pump body The adhesions found in this paper confirm that bacteria grow and contaminate everywhere Therefore, GMP attaches great importance to the cleaning and monitoring of intermediate equipment and links in pharmaceutical system As for where to clean, how to clean, how to clean, how to clean, and cleaning effect, we should also consider the function Association of CIP for those that need cleaning or are not easy to clean, so that outstanding CIP design will continue to produce (3) Online monitoring and control function It mainly refers to that the equipment has the functions of analysis and processing system, which can automatically complete several work steps or processes, which is also the premise of equipment connection, linkage operation and control GMP requires that the production of drugs should be continuous and the process transmission time Zui is short But at present, it is difficult to achieve this requirement when there are many pure machines and single functional equipment At the same time, it has the advantage of expanding this function How to reduce the transmission, turnover and interval, reduce the contact between people and drugs, and shorten the time of drug exposure should be an important guiding ideology in equipment design and equipment improvement The practice also proved that in the pharmaceutical process, the coordinated connection and online control function of the equipment are Zui effective The on-line function of the equipment depends on the application of the integration technology of machine, electricity and instrument With the design of industrial PC, measurement, display and analysis instrument