[exclusive] injection reference preparation selection skills and common mistakes (with reference preparation summary)

On December 22, 2017, CDE organized the drafting of technical requirements for conformity assessment of listed chemical generic drugs (injections) (Draft for comments) to solicit opinions from the public "Draft for comments" describes the selection of the reference preparation as follows: the original product as the reference preparation shall have complete and sufficient safety and effectiveness data as the listing basis If it meets the above requirements, it is recommended that the enterprise select the reference preparation in the following order: （1） The first choice is the original research drug that is listed in China; if the original research drug is not listed in China, the original research drug that has been listed in Europe, America and Japan should be selected (for the original research drug that has been approved to be listed in the United States, the European Union and Japan in turn are recommended) If the prescription of the original research drug is inconsistent in the foreign market, the applicant shall evaluate according to the existing technical requirements and select a more reasonable original research drug （2） In the case that the original research enterprise stops production, the medicine marked RS in American orange book can be selected （3） If there is any doubt about the selection of reference preparation (except for patent issues), it can be determined through discussion with the consistency evaluation office of the general administration Combined with the principle of reference preparation selection of oral solid preparation, the reference preparation of injection is relatively clear and simple Generally speaking, on the basis of meeting the safety and effectiveness, priority should be given to the original research drugs listed in China, including the original research import and the original research real estate; secondly, the original research drugs listed in foreign countries should be selected; the original research enterprises should stop production and then select rs Recently, the author has combed the reference preparations, and some feelings, and made some comments on the selection techniques and common misunderstandings Selection skills 1 Make full use of the database of imported drugs and trace their registration information when necessary 2 According to the initial determination of the listing time of the original research enterprise, focus on the listing time of the United States, the European Union (Member States) and Japan 3 The original research situation will be mentioned in the "development process" section of if document of Japan 4 Patent licensing, joint development, market licensing, etc need to be distinguished 5 The relationship between enterprises needs to be clarified, especially acquisition and merger For example: Hoechst Marion Roussel (subsequency Aventis, now Sanofi) and Fujisawa (now astralas) 6 Refer to the reference preparation filing information of other enterprises Common misunderstandings: 1 The original research of compound is confused with that of preparation 2 Ignore the original research and development varieties 3 XXX for injection and XXX injection should be distinguished For example: docetaxel injection 1 Use the comprehensive retrieval of drug intelligence data to view the injection information, focusing on market information 2 Enter the imported drug database to check the company name, specification, importing country and other information, and obtain the English name of injection (if known, the English name can be omitted) 3 There are two methods to determine whether the import enterprise is the original research enterprise: A determine according to the listing time; B use the original research enterprise column of "global drug R & D database" to check the original research of the compound to prove In order to ensure more comprehensive query information, it is recommended to use Chinese / English active ingredients for retrieval, namely docetaxel / docetaxel Results: A FDA has 51 pieces of information, of which sanofiaventisus was the first listed on May 14, 1996 b EU EMA has 9 pieces of information, among which Aventis Pharma S.A was first listed on November 27, 1995 C Japan PMDA has 40 pieces of information, of which サノフィィ Co., Ltd (Sanofi Co., Ltd.) was first listed in June 1997 Therefore, it can be concluded that Aventis is the original research enterprise At the same time, "global drug R & D database" also found that the original research enterprise was Aventis pharma 4 It can be further determined through other data sources, such as if document in Japan, which also mentions that docetaxel was originally developed by Sanofi 5 By querying whether there are local varieties of domestic drugs, we can see that 37 approval documents of docetaxel injection are all subordinate to domestic enterprises To sum up: the reference preparation of docetaxel injection is Taxotere imported from France The company name is Aventis Pharma S.A the specifications are: 0.5ml: 20mg, 1.0ml: 20mg, 4.0mL: 80mg For domestic specific 1.5ml: 60mg, the specification needs to be changed; for domestic reference preparation 2.0ml: 80mg, the EU listed taxitere needs to be selected In addition, there are 160mg / 8ml docetaxel injection in the EU and the US The selection of reference preparation for docetaxel injection is relatively simple, and some varieties need to be traced back to historical approval information and consult information In this paper, the original research and development varieties, the United States, Europe and Japan listed and the United States Orange Book RS varieties are no longer analyzed by examples As of June 15, there were 210 acceptance numbers for quality and efficacy evaluation of generic drugs, including 35 injections, accounting for 16.67% The pharmaceutical intelligence data is used by the service enterprises to carry out the consistency evaluation of injections, and organize personnel to sort out the original research enterprises and reference preparations of existing injections in China for the reference of enterprises This is the second announcement, with 118 regulations in total; 200 regulations have been announced for the first time, and will continue to be announced in batches later The way of obtaining: the reply to the injections in the official account can get the complete "Excel documents of the 118 injections, the original research enterprises and the reference preparations (second batches)" The first document of the "first batch" of the "200 injections drugs" will be obtained from the first batch of Excel documents You can also visit Yaozhi China orange peel book (folk Edition) database for query At the end of the paper, it is recommended that: 200 injection original research enterprises and reference preparations summary