Opportunities and challenges coexist in the development of bio innovative drugs in China

1 According to the official CFDA and drug delivery database, CFDA has approved a total of 32 Chinese class 1 biological drugs since 2001 and up to August 2018 (see Table 1: approval of Chinese class 1 biological drugs for details) Figure 1 data source of approved number of class 1 biopharmaceuticals over the years in China: CFDA official website, drug delivery database from the perspective of treatment field, approved class 1 biopharmaceuticals mainly focus on cardiovascular, infection, nervous system, digestive system and tumor drugs There are 7 drugs for infectious diseases, 6 drugs for cardiovascular and cerebrovascular diseases, 4 drugs for tumor, 4 drugs for nervous system diseases, 4 drugs for digestive system diseases, 3 drugs for skin diseases, 1 drug for endocrine and metabolic diseases, 1 drug for blood system diseases and 3 drugs for other fields Fig 2 the distribution of indications of bio innovative drugs in China from the perspective of category 1 bio drugs, the approved category 1 bio drugs are mainly concentrated on recombinant cytokines and vaccines There are 10 recombinant cytokines, 8 vaccine preparations, 2 recombinant enzymes, 2 recombinant polypeptides, 1 recombinant hormone, 1 complete antibody, 1 Fab fragment antibody, 1 fusion protein, 1 oncolytic virus and 1 microbial extract Although the number of class 1 new biological drugs approved in China is considerable, most of them have strong Chinese characteristics, lack of core competitiveness and duplication In the global drug market, the proportion of biological drugs is higher and higher Taking the top 10 drugs sold in 2017 as an example, biological drugs occupy 7 places, including adalimumab, enalapril, infliximab (TNF α mAb and fusion protein), trastuzumab, bevacizumab, rituximab (three mAbs of Roche's tumor), opdivo (PD-1 mAb) On the other hand, in the Chinese market, none of the top ten drugs on sale are biological drugs, pure chemical drugs and infusion media The world's best-selling biological drugs are also concentrated in the field of tumor and autoimmune diseases, while the class 1 new drugs approved by China are concentrated in the nervous system and cardiovascular system For example, the most approved class 1 new biological drug in China is rat nerve growth factor for NGFR, which has been listed in five biological drugs in China at present, namely, likanle ®, Nobex ® / enjingfu ®, sutipsen ®, enjingfu ®, and Jinlujie ® However, there is no drug listed in FDA, and there are very few research projects 2 The development process of bio innovative drugs in the world is divided into four stages according to the structure category: Fig 3 the development process of global bio innovative drugs, while the development of China's bio drugs is relatively backward The first stage of the trial started in 1990, and then it has been in a state of lagging generation for a long time At the beginning of the 21st century, China is still in the second stage In terms of approval of class 1 biological drugs, most of them are recombinant proteins and vaccines With the launch of a series of new drug policies, the influx of capital at home and abroad, and the return of a large number of talents in 15 years, biological research and development has entered a stage of vigorous development At present, China has skipped three stages of development, and developed simultaneously in three or four stages It has gradually narrowed the gap in the hot research areas such as car-t, PD-1 inhibitors and bispecific antibodies, and is in the catch-up stage It is believed that in the next five years, more class 1 new biological drugs will be approved, and class 1 new biological drugs in China will be blowout China's emphasis on biopharmaceutical innovation is different from that of chemical drugs and traditional Chinese medicine It has more stringent requirements on the level of biotechnology, which belongs to the knowledge intensive, science and technology frontier fields Therefore, it is easy to form industry barriers, and the benefits are more abundant The difficulty of small molecule drug synthesis process is low, and the sales of chemical original drugs will decline sharply after the patent expires, commonly known as the patent cliff, while the sales of biological drugs will not decline too much after the patent expires due to technical barriers Take insulin glargine, the representative drug of Sanofi's third-generation insulin, as an example After the expiration of the patent, the sales of insulin glargine did not decline dramatically; while imatinib, the most famous tumor targeting drug, fell by more than 50% within one year after the expiration of the patent There is no doubt that the biological industry has become a new industry with the most active innovation, the most rapid development, the most bright future and the most far-reaching impact in the 21st century The biological medicine has gradually become the largest pillar field of the global drug market by anti hyperchemical drugs in the market China also takes Biopharmaceutics as the main direction of strategic emerging industries During the 12th Five Year Plan period, the state will give priority to biological drugs such as monoclonal antibodies, new vaccines and recombinant proteins Among the eight measures proposed in the 13th five year plan to "promote the construction of a healthy China", biomedicine is the top priority In 2016, the state issued the 2016-2020 plan for the revitalization of the biomedical industry, which requires accelerating the promotion of the biological industry as a pillar industry of the national economy, accelerating the integration of the biological industry and other industries, and accelerating the development of targeted drugs, immunotherapy and other technologies The innovation and development of biomedicine has entered the strategic level of China It is the entry point for the Chinese pharmaceutical industry to realize globalization, and the development core of the future strong country of science and technology In contrast, the state's preferential policies on the approval of biopharmaceutical innovation have promoted the development of biopharmaceuticals in China CFDA has launched MAH system, application guide and priority review policies for biological similar drugs The intention is very clear: accelerate the registration system for biological products, encourage enterprises to go out of the country to participate in the road of global innovation, and improve the competitiveness of Chinese pharmaceutical enterprises in new drug research and development.