Excellent experience sharing of new drug special evaluation system in the United States

The United States has a very significant global leading position in the field of pharmaceutical innovation, and is the country with the strongest ability of new drug research and development in the world Since the special evaluation system of new drugs in the United States was established earlier and relatively more mature, it has many references for China In 2018, the U.S FDA approved a total of 59 new drugs, the largest number of new drug approvals in the past 26 years, reflecting the policy tendency of the U.S government to optimize regulation and accelerate the listing of new drugs 1、 A survey of the special review system of new drugs in the United States the United States has set up a variety of new drug special review models based on its own national conditions There are four ways for FDA to speed up the approval of new drugs: fast track, accelerated approval, breakthrough therapy and priority review 1 Fast track: for the treatment of serious diseases and the lack of clinical medication, new drugs for serious diseases include representative AIDS, heart failure, cancer and Alzheimer's disease, as well as epilepsy, depression and diabetes Addressing unmet medical needs refers to the provision of a new therapeutic drug or a therapeutic drug superior to existing drugs Pharmaceutical companies take the initiative to apply for fast track designation, which can be submitted together with the clinical research application (ind), or at any time after the IND is submitted However, it is recommended that FDA give a reply within 60 days after receiving the application before the meeting of biological product licensing application (BLA) or new drug application (NDA) Fast track needs to provide non clinical and clinical data, indicating that the drug has the potential to solve the lack of medical needs Insufficient medical needs can be divided into the provision of currently unavailable treatment drugs or the provision of drugs superior to the existing treatment 2 Accelerated examination and approval: new drugs approved based on alternative end-point for current clinical drug use vacancy can be accelerated examination and approval if they meet the following three conditions: first, they are used to treat serious diseases; second, they have advantages for existing therapies; third, they show new drugs with improved agent end-point performance The applicant shall communicate with FDA reviewers in the process of new drug research and development to explore the application of proxy endpoint indicators, as well as related issues such as confirmatory clinical trials (clinical trials after new drug approval) There is no clear time limit for FDA to respond to accelerated approval applications 3 Breakthrough therapy: new drugs that significantly improve the existing therapy meet the following two conditions can be identified as breakthrough therapy drugs: first, the indications are life-threatening or serious diseases; second, there is evidence that they are significantly better than the existing drugs at an important clinical end point Pharmaceutical enterprises may submit the application for the qualification of breakthrough therapeutic drugs together with the ind, or at any stage after the IND is submitted, but it is suggested that it shall not be later than the end of the phase II clinical trial meeting, and FDA shall reply within 60 days after receiving the application If the drug no longer qualifies for the breakthrough drug designation, FDA will revoke the designation Breakthrough drugs need to provide preliminary clinical evidence that the drug can substantially improve the clinical end point of existing drugs 4 Priority review: new drugs reviewed within 6 months after application acceptance Priority review is applicable to new drugs that treat serious diseases and improve the safety or effectiveness of existing therapies significantly once approved (it can be the first new drug application or supplementary application for the efficacy of drugs already on the market), as well as new drugs identified as anti infective drugs or new drugs for the treatment of some tropical diseases When submitting a new drug production application (NDA), or a biological product production application (BLA), or a related supplementary application, the application shall be reviewed first FDA will reply within 60 days after receiving the application and complete the review within 6 months 2、 In recent years, China has issued a series of documents to establish and improve the new drug special review system 2 2 From the perspective of mechanism, the review mechanism adopted by China and the United States is basically the same, that is, priority allocation of resources for priority review of new drugs Due to the early establishment and relative maturity of the new drug special review system in the United States, there are many references for China: (1) speed up the review by refining the time nodes of key review steps The special approval system of new drugs in the United States has set up several important review nodes, such as filing meeting and mid-term meeting, so as to shorten the time of new drug approval (2) Implement the new drug review project manager system, reduce the communication cost and improve the review efficiency A new drug review project manager is established in the United States to contact and coordinate applicants and review agencies to facilitate the review (3) We will establish specialized review rooms in different areas to enhance the professionalism and scientificity of the review According to different indications, the United States has established a number of evaluation offices for hematology, tumor, metabolism and endocrine Each review room is composed of project manager, pharmacology / toxicology expert, clinical pharmacology / Biopharmaceutics expert, Chemist / biologist expert, medical personnel and statistics expert Through the full exchange and cooperation of experts in different fields, the scientificity of review decision-making can be ensured 3、 Suggestions for improving China's new drug special review system 1 Set a more clear time node for new drug special review The current new drug special review system has made some provisions for the time limit of drug inspection, on-site inspection and communication, but the time limit for the entire technical review has not been clearly defined, and the implementation of the system has certain randomness It is suggested that the overall review time limit of special review should be set, and the review time limit of important nodes such as "Filing review", "technical review report", "three in one comprehensive review", and "approved for listing" should be defined 2 To optimize the classification standard of the scope of application of new drug special review, the current classification standard of the scope of application of new drug special review system in China is still not clear enough There are not only classification standards based on indications and structure, but also drugs of national major new drug development projects and national key R & D plans and varieties voluntarily withdrawn and re declared In the future, it is necessary to further clarify the classification standards of application scope, so as to avoid all kinds of applications crowding in the same channel, which to some extent increases the difficulty of supervision It can be considered that the innovative drugs and improved new drugs should be managed according to the new drug channel, and the first generic drugs urgently needed in clinic should be managed according to the generic drug channel, so as to implement differentiated management on the innovative drugs and generic drugs from the source Due to the relatively small number of innovative drugs in China in a short period of time, it is suggested to pay more attention to improved new drugs and appropriately increase the proportion of improved new drugs 3 Strengthen the construction of relevant supporting systems for new drug special review, continue to explore the establishment of new drug special review project manager system, expand the functional scope of the project manager, take charge of the review process together with the review team, coordinate the exchange between the applicant and the review agency, manage relevant review documents, and fully participate in all aspects of the review process To explore the establishment of a professional evaluation team for indications with clinical reviewers as the core, and with the participation of multi-disciplinary reviewers such as pharmacology, toxicology, pharmacy and statistics and project management personnel, so as to improve the scientificity and rationality of evaluation decision-making (BIOON Com)