Under the new medical policy, the road to survival and development of antibiotic raw material medicine enterprises

Guide

In this paper, datomycin is used as a case to share the challenges and opportunities of current antibiotic APIs, especially the current policies of environmental protection, medical new policy and science and innovation, and the state encourages innovation and squeezes. Under the situation of the marketing expenses of drugs, how do pharmaceutical companies build technical highlands and environmentally friendly highlands? This article provides some useful references and experiences for everyone.

Daptomycin is a novel cyclolipopeptide antibiotic obtained from the fermentation of Streptococcus mutans. It not only works on most clinically relevant Gram-positive bacteria, but also methicillin-resistant in vitro. Isolated strains such as vancomycin and linezolid exhibit strong activity, which is of great significance for clinically saving patients with critically ill infections.

As early as the end of the 20th century, daptomycin was first developed by Eli Lilly and Company. After 2015, Haizheng Pharmaceutical, Huadong Pharmaceutical, Jiangsu Hengrui, Huabei Pharmaceutical and Zhejiang Pharmaceutical successively obtained CFDA's API production. Approval. According to statistics, the global sales of daptomycin has increased rapidly in recent years. As of 2016, it has reached 1.937 billion US dollars. It is expected that the market size of datomycin in the next few years will show an increasing trend year by year.

Daptomycin global sales statistics in recent years

Current challenges in daptomycin purification

Innovative separation and purification processes are effective means to reduce costs and improve economic efficiency. They are also environmentally friendly requirements for reducing environmental waste or chemical emissions.

Improve purification efficiency: Since the nature of antibiotics is closely related to its structure, the experimental conditions should be determined according to the stability of the target antibiotics, avoiding the degradation of antibiotics during the separation process, structural transformation, biological activity reduction, etc., and then according to physical and chemical properties, The separation mechanism selects the optimal purification method to achieve higher product purity and yield and a smaller purification cycle, which is the most critical prerequisite for the purification of antibiotics including daptomycin.

Increased production efficiency: During the purification process, the soft rubber packing of the traditional agarose or dextran matrix is ​​limited by the flow rate and column pressure, and can not be filled with higher column height, which will greatly reduce equipment utilization and production efficiency. In addition, the traditional soft rubber is easy to form a serious adsorption with the impurity pigment after use, and the regeneration is difficult and can not be used after several times, and the life of the filler is severely limited, which greatly increases the input cost of the enterprise. Due to the high price of daptomycin, which limits its sales growth in the world, especially in China, the maximum cost reduction in the process of R&D and production by pharmaceutical companies will significantly reverse this situation and adopt a new chromatographic separation. Fillers and innovative purification processes to reduce separation and purification costs are undoubtedly key.

Environmental protection requirements: The main sources of pollution in industrial separation and purification include waste fillers and mobile phase waste liquids. In order to better meet the stringent requirements of the country in the field of environmental protection, only fillers with longer life and better separation performance can be significantly reduced. The amount of waste material to be disposed of can only greatly reduce the difficulty and cost of subsequent waste liquid treatment by adopting an environmentally friendly mobile phase solution. At present, many enterprises still face major challenges in the above two aspects.

"4+7" drug consumption procurement policy forced enterprises to innovate production technology

The so-called “4+7” drug procurement is to carry out centralized drug procurement in 11 pilot cities, and 31 varieties (42 product specifications) have been identified. The original research or generic drugs that pass the consistency evaluation can participate in the declaration. . The quantity purchase is to promise the sales volume of the medicine at the time of bidding, and it is guaranteed to be used within 8-15 months, that is, “to purchase quantity, to change the price”.

It is foreseeable that the next large-volume procurement policy will be pushed to all provinces and cities nationwide, and the number of pharmaceutical products will continue to expand. Therefore, for the majority of pharmaceutical companies, it is more efficient to use more cost-effective production materials and upgrade innovation. Production technology will undoubtedly become the best strategy.