How to carry out clinical trials of new 3 generic drugs?

May 20 is the 11th international clinical trial day The results of clinical trials are the gold standard to judge the safety and effectiveness of a drug Since 2015, a series of CFDA's publications can clearly see that China's emphasis on clinical trials has increased to an unprecedented level The word "unprecedented" seems to express strongly, but in fact, it's not because China's pharmaceutical industry has not really paid attention to clinical trials before, and "unprecedented" is not great Since clinical trials are so important and so expensive, most of the money spent on research and development of a drug is spent on clinical trials, so whether a drug needs to carry out clinical trials has naturally become a topic of concern for everyone Today we are going to discuss whether the new three categories need to carry out clinical trials (including bioequivalence be trials), and how to carry out them With the reform of drug registration and classification in our country, the original three categories of new drugs (drugs that have been listed overseas but not yet listed in China) are classified as the new three categories of generic drugs (drugs that have been listed overseas but not yet listed in China) Although they are the same three categories and have not changed much in nature, the "administrative level" has changed from "new drugs" to "generic drugs" Can the new 3 categories of generic drugs be exempted from clinical trials and enjoy the treatment of generic drugs? In the work plan for the reform of the registration and classification of chemical drugs, it is said that "the newly registered drugs of categories 3 and 4 shall be declared in accordance with the procedures for generic drugs in the measures for the administration of drug registration" According to the standards of drug registration and classification and the requirements of declaration, there is no essential difference between the new 3 and 4 categories of drugs Can the new 3 categories be directly reported for production according to the bioequivalence test (or even exemption) of generic drugs? Moreover, according to the CFDA announcement on the filing management of chemical drug bioequivalence test (2015 No 257), from December 1, 2015, the chemical drug bioequivalence test (hereinafter referred to as be) was changed from the approval system to the filing management Does that mean that the new 3 categories can also be filed by enterprises and be can be applied for production? How efficient is it to report one batch? In fact, this is just wishful thinking Until May 4, the General Administration issued the requirements for the application materials of new registration and classification of chemical drugs (for Trial Implementation), which failed Through interpretation, it will be found that although the new 3 and 4 categories are both generic drugs, the requirements are different The document clearly states that: For the drugs registered in Category 3, the applicant shall submit the clinical research and development plan and specific clinical trial scheme according to the evaluation of the clinical trial literature and the requirements of the current laws and regulations If there is a good clinical data base, the requirements of clinical trials are relatively less; if the data base of clinical trials is weak or lacking, the effectiveness and safety of drugs shall be studied through clinical trials and / or non clinical trials according to the technical requirements of new drugs For the oral solid preparations registered in Category 3, when submitting the clinical trial application, the applicant shall submit the bioequivalence filing data of the research drug and the completed bioequivalence Research Report in the clinical trial report So why are new 3 and new 4 generic drugs? The difference between the two requirements is still so big At first, Zhijun thought that since they are generic drugs, there is no essential difference in whether they are listed in China, and now more emphasis is placed on the consistency with the original research rather than the differences of ethnic groups Then they should be treated equally and implemented according to the requirements of new 4 Later, we gradually realized that there are great differences between the two One of the important points is that if it is a new four categories of generic drugs, CFDA has a complete set of original research data In drug review, we can use the data and knowledge of the original research to review generic drugs Through comparison, we can find some problems of generic drugs and ensure the quality of generic drugs In Europe and the United States, a special test data protection system has also been established, that is, FDA has read the original research data and can not use this data knowledge to evaluate generic drugs within 5-10 years (that is, a market monopoly period has been formed) As for the new three categories, CFDA review experts do not fully understand the drug and review according to the requirements of generic drugs without relevant data and information, which may lead to blind spots or misunderstandings Let's take a look at the minutes of a forum on the Internet: With regard to the application of the new 3 types of oral solid preparations, director Yang of the chemical and Pharmaceutical Department explained: referring to document 44 and document 257, the applicant should carry out be experiment after going through the filing formalities, prepare the data according to the application production requirements after completion, and approve the result of be directly in the technical review; if there are still problems, clinical approval documents will be issued, and PK + 100 pair of clinical trials will be carried out 。 (as for whether injection products can be directly applied for production, after the meeting, the teachers of the registration department and the evaluation center were consulted respectively The former thought that as long as the applicant completed the relevant pharmaceutical comparative study and met the technical evaluation requirements, the production could be directly approved, but the latter thought that the evaluation standard of order 28 could not be reduced, so a confirmatory clinical study should be carried out, which needs to be discussed.) 。 From the minutes of this meeting, including the discussion of some friends in the group, it can be seen that whether and how to conduct clinical trials for the new three categories are still controversial in the industry Although in principle clinical trials are required in the requirements for new registration and classification of chemical drugs (the author expects that be + 100 may be the mainstream of clinical trials), it is not very clear, What's more, we need to determine what kind of clinical trial to carry out according to the guiding principles in a scientific manner, and what kind of role the clinical trial can really play, so that we can afford the money spent and the patients participating in the trial.