According to the classification of the World Health Organization (WHO), antibacteriological agents for systemic use are usually divided into 8 subclasses, namely, cefazoles, penicillins, macrolids and linkers, aminoglycosides, quinolones, carbapenems, nitroimidazoles and other anti-infective agents. At present, -lactam antibiotics dominated by penicillin and cephalosporin account for 70% of the global antibiotic market.
The top three drug varieties in China's pharmaceutical market are anti-infective drugs for general use, anti-tumor and immunomodulatory agents and cardiovascular system drugs. In 2018, the yield of major intermediates of antibiotics increased to varying degrees except for the decrease of ceftriaxone koosin and levophosphate used to produce fosfomycin series products. The salt output of penicillin industry increased by 10% year on year, and the supply and export volume decreased by 24.5% year on year. The output and export volume of Six manufacturers, Namely, National Medicine, Shiyao and Inner Mongolia Changsheng Pharmaceutical, all decreased year on year. The output of Harbin Pharmaceutical General Factory, Huabei Pharmaceutical and Kelun Chuanning bio-pharmaceutical increased by more than 30% year on year. The yield of 7ACA increased by 3.2% year on year, the yield of national drug Wichita decreased by 4%, the yield of stone drug increased by 23%, and the yield of Collenthrin biological increased by 81%. The yield of koshi ceftriaxone salt decreased by 58.2%, and all of the five production enterprises decreased except shandong Lukang production increase.
2. Industrial chain and competition pattern
The upstream of the antibiotic pharmaceutical intermediates industry is mainly the basic chemical raw material production industry, while the downstream is the antibiotics bulk drug and preparation industry. Basic chemical raw materials, antibiotic pharmaceutical intermediates, and antibiotic bulk drugs and preparations constitute a complete industrial chain of antibiotic pharmaceutical industry.
The industrial chain
Upstream of the antibiotic pharmaceutical intermediates are basic chemical raw materials, most of the chemical products for oil, with the support of national overall regulation and policies, and further optimize product structure, basic chemical industry in China most basic chemical raw materials can meet the demand of domestic production, for the antibiotic pharmaceutical intermediates industry continued stable development has laid a good foundation.
The pharmaceutical intermediates of antibiotics are located in the middle and lower reaches of the whole chemical industry chain, and are closely related to the consumption field of terminal antibiotics drugs. The technological update, policy change and prosperity degree of the pharmaceutical intermediates of antibiotics directly determine the demand for the upstream pharmaceutical intermediates of antibiotics. In addition, some antibiotics API manufacturers are directly engaged in the production of intermediates, which will also have a certain impact on the pattern of antibiotic intermediates industry. As a major producer and supplier of API in the world, China can produce more than 1,500 kinds of API at present, among which the output of many varieties ranks first in the world. At the same time, China is also the world's largest exporter of API. 90% of China's API is supplied to overseas markets, accounting for about 25% of the global VOLUME of API trade.
In the early stage of development of the domestic antibiotic pharmaceutical intermediates industry, the manufacturers are mainly small and medium-sized private enterprises, mostly engaged in the production and sales of pharmaceutical intermediates with low technical level and low capital investment. The whole industry presents an extensive development mode characterized by "many, small, scattered and chaotic", and the market concentration degree needs to be improved. With the development of national economy, the domestic industry of antibiotic medicine intermediates has increased the exchange and cooperation with foreign enterprises, the overall technical level has been continuously improved, and the enterprise scale has been gradually expanded.
Antibiotics "limit" policy since 2011, the clinical application of antibacterial drugs classification management, special activities to expand to the specialized subject hospital system, such as ground, make the clinical use of antimicrobial agents decreased obviously, antibiotic intermediates products price downturn has also led to part of the state-owned large and medium-sized enterprises take the initiative to withdraw from the market; In addition to the intensification of environmental protection governance in China in recent years, the substantial increase of environmental protection investment and human resource cost of enterprises in the industry also promotes the integration within the industry to a certain extent. From the perspective of medium and long term development, in the future, the merger and elimination of enterprises in the pharmaceutical intermediates industry will be more frequent, and the competition among enterprises will be more intense, and the pharmaceutical intermediates industry is undergoing a reform process from decentralization to centralization.
In 2018, under the influence of increasingly stringent domestic environmental protection policies, increasing requirements for energy conservation and emission reduction as well as safety and environmental protection, enterprises in the industry have been deeply affected, with rising product costs and limited product production capacity. A large number of small and medium-sized enterprises are facing the pressure of closing down or eliminating their products. A new API factors of competition has gradually from the past in the field of production scale and cost competition, to environmental pollution control, cleaner production process and the resulting product quality advantages such as "green" competitive power shift, so the compliance enterprises are also great opportunities for development, product sales prices, as in the enterprise, our opportunities and challenges coexist.
3. High technical and environmental protection barriers
(1) Technical level barrier
As the pharmaceutical intermediates of antibiotics are technology-intensive industries, the development of key intermediates is difficult and the monopoly of core technologies is strong. Pharmaceutical intermediates manufacturers should have strong and continuous r&d strength to meet the demand of downstream product upgrading. In addition, the choice of core technology, process flow, equipment and key reactants as well as the difference in process control will affect the quality and yield of the final product.
With the increase of labor cost and the improvement of environmental protection standards, companies using different technologies also have great differences in cost control and pollution reduction. In the industry chain of antibiotic medicine, only those enterprises with independent research and development ability, core technology, cost and generation control competitiveness can continue to develop in the industry. For new entrants, advanced and production technology and process control can guarantee the quality of products, and there are high technical barriers.
(2) Environmental protection barriers
With the deepening of the concept of sustainable development and the optimization and upgrading of industrial structure, the national environmental protection requirements for chemical enterprises are increasingly strict, and the green production process and environmental pollution control standards for the antibiotic medicine intermediate industry are constantly improved. It is required that the production site of chemical enterprises must be located in the specified chemical industry park. When investing in the construction of new projects, "environmental impact assessment" shall be carried out in advance. Land use shall not be approved, loans shall not be granted or credit shall not be granted in any other form for planning and construction projects that have not been subjected to environmental impact assessment or have not been approved by environmental impact assessment.
The design and construction of environmental protection facilities must be designed, constructed and put into operation at the same time as the main projects; In the process of product production process design, enterprises also need to reasonably design post-natal treatment process and "three wastes" treatment arrangement. In the medium and long term, the high standard of national environmental protection is undoubtedly an insurmountable barrier for new entrants in the antibiotic intermediate industry, which also means that small enterprises without green core production technology and scale cost advantage in the industry will find it difficult to survive and develop.