API refers to the active ingredients obtained by chemical synthesis, semi-synthesis, microbial fermentation or natural product separation, and made by one or more chemical unit reaction machines for the manufacture of pharmaceutical preparations. In the drug research and development process of API, the comprehensive analysis of the process is one of the important contents, through the comprehensive analysis can make the drug developers have a clear understanding of the advantages and disadvantages of the whole process, but also conducive to the technical evaluation of drugs. At present, China's API has shown a strong growth trend, but it is also facing the dual pressure of high cost and low quality. How to effectively control the cost of API is also one of the concerns of enterprises.

Drug research and development is a very great work, which has a great impact on human health, so its process is relatively complicated. Medisi Biopharma is a preclinical pharmaceutical R & D outsourcing service company that specializes in providing customizable preclinical trial service programs with expertise in drug metabolism, pharmacokinetics, pharmacodynamic studies, and toxicology.

1, API drug development process is as follows:

(1) Identification of target compounds

Through literature research, pharmacodynamic screening experiments or other related basic research work, the target compounds to be developed are determined.

(2) Design of synthetic route

According to the structural characteristics of the target compound, referring to the relevant literature at home and abroad, the synthetic route with feasible process, reasonable cost and relatively high yield was determined. The analytical method plays the role of a "beacon" in the drug development process, and is the ruler and eye for the development and quality control of APIs and preparations, so the analytical method plays the role of a navigator in the drug development process. Before starting the development of analytical methods, it is necessary to obtain the synthetic route provided by the starting material manufacturer, including the following points: starting materials, intermediates, reaction solvents, post-treatment solvents and key catalysts. If the reaction steps provided by the manufacturer are too long, generally 3-5 steps can be selected.

(3) Preparation of target compound

Through chemical reaction, biological fermentation or other methods to prepare the quality of the target compounds to meet the requirements, for the product structure confirmation, quality control and other pharmaceutical research, as well as pharmacological toxicology and clinical research to provide qualified samples.

(4) Structural confirmation

The structure of the target compound was confirmed using physical and chemical methods.

(5) Process optimization

The production process is optimized by considering the ease of obtaining raw materials, reaction conditions of the process route, environmental protection and safety, and product purification. The optimization of the synthetic process of API should comprehensively analyze all the synthetic processes reported in the literature, give priority to the route of the original research manufacturer, if it is barrier-free, and analyze the advantages and disadvantages of all barrier-free routes in detail, and design their own brand-new route by combining the advantages and disadvantages of several routes.

(6) Pilot study and industrial production

Through the research of pilot and industrial production process, a stable and feasible process is determined, which can provide raw materials that meet the requirements for further research and development of drugs.

2, the cost composition of API.

The overall cost composition of API can be divided into materials, labor and expenses, I .e. raw material costs, personnel wages and manufacturing costs. There are three main factors that lead to the high cost of API.

(1) The price of basic chemical raw materials continues to rise, squeezing the profit margin of API.

In recent years, due to the gradual increase in the price of international crude oil market, the price of its derivatives has risen. Commonly used solvent raw materials such as benzene, toluene, ethyl acetate and acetone have all risen by more than 10%, causing some companies to be overwhelmed and switch production and reduce production. Even stop production. The reason is that in the cost structure, the cost of raw materials accounts for about the absolute proportion of the total cost, the most direct and huge impact, therefore, the soaring price of raw materials greatly squeezed the profit margin. In the context of the general rise in the prices of basic raw materials, some purchasers lack rational thinking about the price rise and fall of raw materials, follow the trend and often miss the best time to purchase, which will also lead to high prices of raw materials.

(2) The capital cost pressure brought about by the production cycle of the API.

The long production cycle of API is determined by its characteristics. The synthesis of API is a complex chemical process rather than a physical process, which requires time and conditions. From the beginning of the raw material storage inspection to the finished product inspection, even if the chemical reaction with the least steps is conservatively estimated to take about half a month. From the point of view of on-site mass production, the feeding process is continuous rather than intermittent, so there will be a large number of in-process products in the whole process, coupled with the synthesis of an API required more raw materials, so the long production cycle has become one of the factors causing capital cost pressure.

(3) The increase in labor costs year by year is a foregone conclusion.

The introduction of the annual CPI index and the city average wage line will stimulate employees' demands for wage increases, but when the quality of the enterprise's economic operation does not meet satisfactory expectations, the timing and magnitude of wage increases are often played between the enterprise and the employee. In order to reduce labor costs, enterprises often use labor dispatch, but API production, especially chemical reaction posts, need certain chemical knowledge and experience, through short-term training and rapid education and can not be competent for the job.

(4) Inputs in hardware facilities indirectly translate into costs for APIs

API production requires a large hardware investment, according to the unit reaction to arrange the required equipment, including reaction kettle, storage tank, pipeline and transmission equipment, one-time investment is very considerable. At the same time, because most chemical reactions use three acids, two alkalis, flammable and explosive materials, equipment maintenance also requires capital investment. The annual repair cost of a medium-sized API manufacturing enterprise is more than one million yuan, which is evident in the huge cost. Others, such as environmental protection and safety facilities, require funding. Of course, the cost of equipment and facilities is not all into the cost, but the annual depreciation charge is also reflected in the cost.

There are many factors that cause the high cost of APIs, whether direct or indirect, which cannot be avoided and changed due to the national macro policy guidance, but there are also some subjective internal factors. Starting from strengthening management, transforming and tapping potential, and accelerating product structure adjustment, the cost structure of APIs can be improved, reflecting a certain contribution to gross profit. To control the high cost of API, we can start from the following:(1) source control of raw material prices;(2) process optimization to reduce raw material costs;(3) dynamic post setting to control labor costs;(4) implementation of centralized production to control manufacturing costs;(5) establishment of multi-functional production lines to improve the comprehensive utilization rate of equipment;(6) speed up the pace of international certification and enter the international registered market.