New class 3 declaration is cold! Why are pharmaceutical companies not willing to invest?

Since the release of the consultation draft in November 2015 (the official draft in March 2016) for the reform of chemical drug registration and classification, the new three categories (the domestic applicant imitates the drugs listed overseas but not listed in China) have attracted much attention So in the past two and a half years, how about the declaration of the new three categories? Why injection declaration heat is significantly higher than oral medicine? Is it more convenient to apply for production directly? According to the statistics, there are 73 new registration applications for chemical drugs in 2016, 196 in 2017 and 28 as of May 24, 2018 Since 2017, except for two acceptance numbers or clinical applications, the rest are production applications This is because in the policy interpretation (2) of the work plan for the reform of chemical drug registration and classification released in December 2016, it was determined that the new registration categories 3 and 4 were applied for registration in the form of production declaration Applying for registration in the form of production does not mean that clinical trials are not necessary According to the notice of 2016 (No 80 in 2016) on Issuing the requirements for application materials of new registration classification of chemical drugs (Trial), drug applicants of registration classification 3 need to submit clinical research and development plan and specific clinical trial scheme The clinical trial scheme should be based on the evaluation of the clinical trial literature: if it has a good clinical data base, the clinical trial requirements are relatively less; if the clinical trial data base is weak or lacking, it is necessary to study the effectiveness and safety of drugs through clinical trials and / or non clinical trials according to the technical requirements of new drugs For the application of hot oral medicine < injection, the new 3 types of oral medicine should be made be first, and the policy preferential treatment is limited since the API adopts the related review system, and the new 3 types of application in 2018 also does not include the API Excluding the data of APIs, there were 41 new class 3 registrations in 2016, 100 in 2017, 28 as of May 24, 2018, and 169 in total Through the analysis of 169 acceptance numbers, it can be found that injection still accounts for the largest part, with a total of 86 acceptance numbers This is because when the application for clinical trial is submitted for registration and classification of the new three categories of oral solid preparations, the bioequivalence filing data of the research drug and the completed bioequivalence Research Report shall also be submitted in the clinical trial report As early as December 1, 2015, China began to implement the filing management of chemical drug bioequivalence test, so the new three categories of projects actually started need to refer to the data of be filing The new three types of oral solid preparations for chemical drugs need to complete bioequivalence test first, and then approve the clinical trial scheme according to the clinical trial literature, with large investment, but the corresponding policy preferential treatment is limited 　　 For example, during the protection period of drug test data, according to the implementation measures for the protection of drug test data (Interim) (Draft for comments) issued in April 2018, generic drugs are likely to obtain the protection period in the categories of rare disease treatment drugs, children's special drugs and drugs with successful patent challenges, among which rare disease treatment drugs and children's special drugs have been approved in China for the first time since the indication A six-year data protection period will be granted from the date of the patent challenge, but there is no clear protection period for the drugs that have successfully challenged the patent It is worth noting that the patent related to the original research drug corresponding to the new three generic drugs may not enter China If the patent is not authorized by China, there is no way to talk about the success of the patent challenge, let alone the protection period To sum up, the R & D of new 3 categories of domestic enterprises will tend to injection, or some products with rare disease indications but expected to be used for over indications Rare diseases, new opportunities, 3 kinds of rare diseases, the first list of rare diseases, only 20% of drugs started clinical On May 23, 2018, the announcement of the State Food and Drug Administration and the state health and Health Commission on matters related to the optimization of drug registration review and approval (No 23, 2018) mentioned that "for the drugs that have been listed overseas and have no effective treatment means for diseases and rare diseases, if the applicant for the registration of imported drugs does not have ethnic differences through research, he / she can Directly apply for drug registration by submitting clinical trial data obtained abroad For the above-mentioned import drug clinical trial applications that have been accepted and put forward for clinical trial reduction or exemption before the issuance of this announcement, if they meet the requirements of the measures for the administration of drug registration and relevant documents, they can be directly approved for import " This means that generic drugs with rare diseases also have the opportunity to be listed in China Looking back at the list of priority reviews for rare diseases, it can be found that at present, only dantraline sodium for injection from Lizhu pharmaceutical factory of Lizhu group is generic drug, and the rest are original new drugs There are a relatively large number of manufacturers applying for priority review of generic drugs for children's drug use, including montelukast sodium granules of Changchun Haiyue Pharmaceutical Co., Ltd., aripiprazole oral solution of Sichuan Otsuka Pharmaceutical Co., Ltd., and mefalun for injection of Xi'an Libang Pharmaceutical Co., Ltd On May 22, 2018, the catalogue of the first batch of rare diseases has been released, covering a total of 121 diseases This catalogue is jointly released by the national health and Health Commission, the Ministry of science and technology, the Ministry of industry and information technology, the State Drug Administration, the State Administration of traditional Chinese medicine and other five departments At present, hemophilia, idiopathic pulmonary hypertension, idiopathic pulmonary fibrosis, multiple sclerosis, optic neuritis and so on are the most active indications of drug treatment in China See Table 2 for the drugs that have started clinical treatment for the diseases in the first batch of rare diseases catalogue, which involves 23 kinds of rare diseases, and the rest 98 kinds of rare diseases have not started clinical treatment (accounting for more than 80%) Summary: the main reason for the cold of the new 3 types of oral chemicals is the lack of supporting After the approval of the new 3 categories of domestic chemical drugs, other new 3 categories of registration applications for the product are expected to be approved without confirmatory clinical application Therefore, in addition to the enterprises with strong sales ability willing to be the "leader", most enterprises will choose to complete be and wait for the original research or the first new three types of enterprises to be listed Compared with the cost of confirmatory clinic, the long-term return rate of the first approved new three generic drugs is too low, and the project investment intention of domestic enterprises is not high.