The enthusiasm of applying for imported generic drugs is gradually rising: overseas data sharing is good! Which can pass customs faster?

The spring of overseas generic drugs has come On July 10, 2018, the State Drug Administration issued the notice of "technical guidelines for accepting data of overseas clinical trials of drugs" (No 52, 2018) The overseas clinical trial data involved in the guiding principles include the clinical trial data obtained overseas by the applicant through simultaneous research and development of innovative drugs at home and abroad, as well as the complete and evaluable bioequivalence data This will promote more and more overseas generic drugs (i.e category 5.2 drugs, non original research drugs listed overseas applying for domestic listing) to apply for listing The acceptability of overseas data is good for the opening of overseas data It is necessary to pass the "race" test first to facilitate the simultaneous test between China and foreign countries and the East Asian population test As shown in Table 1, the overseas clinical trial data approved by the State Drug Administration are mainly considered from three aspects: first, the authenticity, integrity, accuracy and traceability of the overseas clinical trial data; second, the effectiveness and safety of the overseas clinical trial data; third, whether there are racial differences in the overseas clinical trial data   　　 Among them, ethnic difference analysis needs to conduct ethnic sensitivity analysis on the regional and ethnic aspects of clinical pharmacology data to determine whether the overseas clinical trial data is applicable to the Chinese population; and to confirm the consistency between the Chinese subgroup and the world population in terms of effectiveness and safety in accordance with the requirements of ICH on ethnic influencing factors (E5) for accepting the overseas clinical data 。 To sum up, If the class 1 imported new drugs (innovative imported drugs that are not listed at home and abroad) have done multi center clinical trials at the same time at home and abroad, the class 5.1 drugs (original research drugs that are listed abroad apply for domestic listing) and the class 5.2 imported generic drugs corresponding to the original research drugs have done the clinical trials of East Asian people, especially the Chinese subgroup, it is expected that the technical guidance on accepting the data of overseas clinical trials of drugs will be provided in the "technical guidance on accepting the data of overseas clinical trials of drugs" Principles In addition, some characteristics of drugs (chemical classification, metabolic pathway or pharmacological classification) determine whether they are susceptible to racial factors Some drug properties will most likely indicate insensitivity to race The drug properties that are not sensitive to race factors include: linear pharmacokinetics (PK); a straight pharmacokinetic curve (PD) within the recommended dose and administration scheme (indicating that the drug has good tolerance); a wide dose range indicating that the drug has good tolerance (few dose changes will not cause great changes in drug effect); less or more metabolism Species metabolism (not increasing the possibility of drug interaction due to only one pathway metabolism); high bioavailability (not affected by dietary absorption); low protein binding rate; small drug drug, drug diet, drug disease interaction; non systemic mode of action; small chance of being improperly used (drugs easy to be improperly used such as analgesia and Sedatives) etc Correspondingly, such as the administration of precursors, especially the transformants of enzymes with potential racial differences, are sensitive to racial factors Referring to ICH, China will strictly supervise the overseas data in the short term In addition, according to the E5 of ICH, China will accept the overseas clinical trial data, and may also consider the following parts: 1) the clinical trial data of special sub population, such as patients with liver and kidney dysfunction, etc 2) adjust the dosage and administration method according to the ethnic group or local treatment; 3) drug interaction study According to the experience of ICH, with the increase of regional recognition experience of clinical data in foreign regions, the drug regulatory department will have a better understanding of the safety and effectiveness of supplementary research, dosage and pharmacodynamic clinical data of drug administration scheme in which cases, and the demand for supplementary research between regions will gradually decrease In view of this, China's drug regulatory bureau may strictly supervise the overseas test data in a short period of time, and countries with high regulatory requirements such as the United States, Japan, the United Kingdom and Germany are relatively more likely to be recognized as the market places of imported drugs Registration application data of class 1, 5.1 and 5.2 PK class 5.2 application enthusiasm is gradually rising According to the data of sea travel of Xianda drugs, after the reform of chemical registration laws and regulations, before 2017, import registration application was mainly based on class 5.1 clinical application and class 1 new drug clinical application In the first half of 2018, class 5.2 clinical application increased 5.2 cefazolin sodium for injection, which is only approved to be imported by Otsuka pharmaceutical, can be regarded as passing the consistency evaluation 5.2 the application involves generic pharmaceutical manufacturers in India, Taiwan, China, Europe and the United States, and the third-party registration and application agencies are mainly used in China For example, Novartis has declared Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation, Levetiracetam Tablets, Mometasone Furoate Nasal Spray, Escitalopram Oxalate Tablets and Voriconazole Tablets India Reddy has declared the sildenafil citrate tablets, Rivaroxaban tablets, Rivaroxaban tablets, carbon acid, vitamin Rahm tablets and acetic acid Albon tablets The recent import approval tide of category 5.1 listing with "fast" channel mainly comes from category 5.1, i.e the original research drugs listed overseas applied for domestic listing In 2017, a total of 15 imported drugs were approved as category 5.1, while in the first half of 2018, there were 8 Yishazomi citrate, the first-line treatment drug for multiple myeloma in Takeda, was approved in 2018 and launched phase III clinical practice in 2017 Although it has not been reported for listing, it has been approved for listing Similar products include Gilead's sophopewectavir tablets The two products are expected to meet the requirements of "National Drug Administration" issued on May 23, 2018 As mentioned in the announcement of the national health and Health Commission on the optimization of matters related to the review and approval of drug registration (No 23, 2018), "for the drugs that have been listed abroad and are seriously life-threatening and have no effective treatment means, and for rare diseases, if the applicant for registration of imported drugs does not have ethnic differences after research, he can submit the clinical trial data obtained abroad directly Application for listing and registration of drugs " That is to say, for these cases, the above-mentioned clinical trial application for imported drugs that have been accepted and put forward for clinical trial exemption or exemption before May 23, 2018, which meets the requirements of the measures for the administration of drug registration and related documents, can be directly approved for import and approved for listing Only one class 1 imported drug is declared for listing From 2016 to the first half of 2018, the only new imported class 1 drug to be declared for market is the second generation of human epidermal growth factor receptor (her) inhibitor, which was applied by Pfizer's dacominib in the first half of 2018 for the first-line drug treatment of patients with advanced non-small cell lung cancer (NSCLC) In conclusion, the introduction of products should also consider the market situation, market scale and price of domestic products From the perspective of national drug use structure, at present, only the imported generic drugs with relatively low price and without generic drugs imported from the original research institute, as well as the imported generic drugs with critical diseases, rare diseases, pediatrics and lack of effective treatment means which are not listed in the domestic market, are more likely to be the goal of accelerating the introduction.