The State Council's Decision on Reforming Medicines and Medical Devices

Opinions on the review and approval system

Guo Fa [2015] No. 44

People's governments of various provinces, autonomous regions, and municipalities directly under the Central Government, as well as various ministries and commissions of the State Council and directly affiliated institutions:

In recent years, China's pharmaceutical industry has developed rapidly, and the quality and standards of pharmaceutical and medical devices have been continuously improved, effectively meeting the needs of the public for medication. At the same time, the problems in the review and approval of pharmaceutical and medical devices are becoming increasingly prominent, with low quality registration application materials and the need for multiple supplements and improvements during the review process, which seriously affects the efficiency of review and approval; The repetitive construction and application of generic drugs result in vicious market competition, and there is a significant gap in the quality of some generic drugs compared to international advanced levels; The approval time for the launch of urgently needed new drugs in clinical practice is too long, and drug research and development institutions and researchers cannot apply for drug registration, which affects the enthusiasm for drug innovation. Therefore, the following opinions are proposed on reforming the review and approval system for pharmaceutical and medical devices:

1、 Main objectives

（1） Improve the quality of review and approval. Establish a more scientific and efficient drug and medical device review and approval system, so that the effectiveness, safety, and quality controllability of approved marketed drugs and medical devices can reach or approach international advanced levels.

（2） Resolve the backlog of registration applications. Strictly control the approval of drugs with oversupply in the market. Strive to eliminate the backlog by the end of 2016, achieve an annual balance of registration applications and review quantities as soon as possible, and achieve approval within the specified time limit in 2018.

（3） Improve the quality of generic drugs. Accelerate the quality consistency evaluation of generic drugs, and strive to complete the quality consistency evaluation of national essential drug oral formulations and reference formulations by the end of 2018.

（4） Encourage research and the creation of new drugs. Encourage clinical value oriented drug innovation, optimize the review and approval process for innovative drugs, and accelerate the review of urgently needed innovative drugs in clinical practice. Pilot the system of drug marketing license holders.

（5） Improve the transparency of review and approval. Fully disclose the acceptance, technical evaluation, product inspection, and on-site inspection conditions and relevant technical requirements for drug and medical device registration, disclose relevant information on acceptance and approval, and guide applicants to conduct orderly research and application.

2、 Main tasks

（6） Improve drug approval standards. Divide drugs into new drugs and generic drugs. Adjust the new drug from the current "drugs that have not been marketed in China" to "drugs that have not been marketed in China or abroad". According to the originality and novelty of the material foundation, new drugs are divided into innovative drugs and improved new drugs. Adjust generic drugs from the current "imitating drugs with existing national standards" to "imitating drugs with the same quality and efficacy as the original research drugs". Adjust the classification of drug registration based on the above principles. The review and approval of generic drugs should use the original drug as a reference formulation to ensure that the quality and efficacy of newly approved generic drugs are consistent with the original drug. Continue to review and approve drug registration applications accepted before the reform in accordance with the original regulations, and gradually solve the problem of consistency with the quality and efficacy of the original drug in the evaluation of quality consistency; If the enterprise voluntarily applies for approval according to new standards that are consistent with the quality and efficacy of the original drug, a green channel can be established to charge according to the new drug registration application fee standard, and to accelerate the review and approval. After obtaining authorization in accordance with legal procedures, the above reforms will be piloted in chemical drugs.

（7） Promote the consistency evaluation of generic drug quality. For generic drugs that have been approved for marketing, quality consistency evaluation shall be conducted in stages and batches based on the principle of consistency with the quality and efficacy of the original drug. Pharmaceutical production enterprises should conduct quality consistency evaluation of their products with reference formulations according to the prescribed methods, and submit the evaluation results to the Food and Drug Administration. The reference formulation is determined by the Food and Drug Administration after consulting expert opinions, and can choose the original research drug or the internationally recognized drug of the same type. For non reference formulations, clinical efficacy trials shall be conducted by drug manufacturers. Generic drugs that have not passed the quality consistency evaluation within the specified period shall not be re registered; Those who pass quality consistency evaluation are allowed to be labeled on the instructions and labels, and support is provided in clinical applications, bidding procurement, medical insurance reimbursement, and other aspects. In the evaluation of quality consistency, if it is necessary to change the approved process, a supplementary application should be submitted in accordance with the relevant provisions of the "Drug Registration Management Measures". The Food and Drug Administration should establish a green channel to accelerate the review and approval. The quality consistency evaluation work was first carried out in generic drugs approved for marketing before the implementation of the revised "Drug Registration Management Measures" in 2007. Mark the name of the pharmaceutical standard drafting enterprise in the national pharmacopoeia to encourage enterprises to improve the standards and quality of marketed drugs through technological progress. Improve the quality level of traditional Chinese patent medicines and simple preparations and actively promote the re evaluation of the safety of traditional Chinese medicine injections.

（8） Accelerate the review and approval of innovative drugs. Implement a special review and approval system for innovative drugs. Accelerate the review and approval of innovative drugs for the prevention and treatment of AIDS, malignant tumors, major infectious diseases, rare diseases and other diseases, drugs listed in major national science and technology projects and national key research and development plans, innovative drugs and drugs for children produced in China, as well as innovative drugs that use advanced preparation technologies, innovative treatment methods and have obvious therapeutic advantages. Accelerate the review and approval of urgently needed new drugs in clinical practice. Enterprises applying for registration of new drugs must promise that their products will not be sold at prices higher than those in the country of origin or comparable markets around China.

（9） Pilot the system of drug marketing license holders. Drug research and development institutions and researchers are allowed to apply for registration of new drugs. When transferring to enterprises for production, only on-site process verification and product inspection of the production enterprise will be conducted, and drug technical evaluation will not be repeated. The pilot work will be carried out after obtaining authorization in accordance with legal procedures.

（10） Implement the applicant's main responsibility. Formulate registration application standards in accordance with international general rules, and applicants must strictly apply in accordance with the prescribed conditions and relevant technical requirements. The drug registration applications currently accepted by the provincial food and drug regulatory department and reviewed and approved by the State Administration of Food and Drug Administration will be adjusted to be centrally accepted online by the State Administration of Food and Drug Administration. For registration applications that do not meet the prescribed conditions and relevant technical requirements, the Food and Drug Administration shall notify the applicant of the necessary supplementary content at once. After entering the technical review process, except for the registration application for new drugs and first generic drugs, in principle, the applicant is no longer required to provide additional information, and only a decision is made to approve or not approve.

（11） Timely release drug supply and demand and registration application information. According to the direction of national industrial structure adjustment and the market supply and demand situation, timely adjust national pharmaceutical industry policies, strictly control the production and approval of generic drugs with oversupply, low-level duplication, and outdated production processes in the market, encourage the research and production of drugs in shortage in the market, and improve the accessibility of drugs. The State Administration of Food and Drug Administration, in conjunction with the Development and Reform Commission, the Ministry of Science and Technology, the Ministry of Industry and Information Technology, and the Health and Family Planning Commission, formulates and regularly publishes approval catalogs for restricted and encouraged drugs. The State Administration of Food and Drug Administration shall promptly disclose drug registration application information to the public, guiding applicants to conduct orderly research and control low-level applications.

（12） Improve drug clinical trial approval. Allow overseas unlisted new drugs to undergo simultaneous clinical trials in China after approval. Encourage domestic clinical trial institutions to participate in international multicenter clinical trials, and eligible trial data can be used in registration applications. For innovative drug clinical trial applications, the focus is on reviewing clinical value and subject protection. Strengthen the responsibility of applicants, clinical trial institutions, and ethics committees to protect subjects.

（13） Serious investigation and punishment of fraudulent registration applications. Strengthen the supervision of the entire clinical trial process to ensure the authenticity and reliability of clinical trial data. If the applicant or research institution submits false research methods, quality standards, pharmacological and toxicological test data, clinical trial results, etc. in their registration application, their drug and medical device registration application will not be approved, and those that have already been approved will be revoked; Strict punishment shall be imposed on the directly responsible person in accordance with the law, and research institutions that issue false test results shall be disqualified from conducting relevant experiments. The punishment results shall be announced to the society.

（14） Simplify the drug approval process and improve the drug re registration system. Implement the associated approval of drugs, pharmaceutical packaging materials, and pharmaceutical excipients, and change the separate approval of pharmaceutical packaging materials and pharmaceutical excipients to be reviewed and approved together when approving drug registration applications. Simplify the approval of compound formulations derived from ancient classic formulas. Simplify the process of drug technology transfer between drug production enterprises. Change the approval of bioequivalence testing for generic drugs to filing. If the approval number (Import Drug Registration Certificate/Pharmaceutical Product Registration Certificate) is not listed within the validity period and cannot fulfill the responsibility of continuous inspection of drug quality, efficacy, and adverse reactions, it will not be re registered. After the approval number expires, it will be cancelled.

（15） Reform the approval method for medical devices. Encourage research and innovation in medical device development, and prioritize the registration of innovative medical devices with core product technology invention patents and significant clinical value within the scope of special review and approval. Timely revise medical device standards, improve the adoption rate of international medical device standards, and improve the quality of domestic medical device products. By adjusting product classification, the registration and approval responsibilities for some mature, safe and controllable medical devices will be delegated from the State Administration of Food and Drug Administration to provincial food and drug regulatory departments.

（16） Establish a sound evaluation quality control system. Develop good evaluation quality management practices based on international general rules. Establish a professional technical review project team, clarify the rights and responsibilities of the main reviewer and reviewers, improve the collective review mechanism, and strengthen responsibility and time limit management. Establish a review expert committee to review controversial review conclusions and ensure that the review results are scientific and fair. Strengthen the research on common and difficult issues in the technical review process, timely convert research results into technical standards to guide the review work, improve the standardization level of review, and reduce the discretion of review.

（17） Fully disclose the review and approval information of drugs and medical devices. Publish the list of drug and medical device approvals, legal basis, approval requirements, and processing time limit to the society. Disclose the progress and results of drug and medical device approval to the applicant. When approving the product marketing license, technical review reports such as review, inspection, and inspection shall be simultaneously released and subject to social supervision.

3、 Safeguard measures

（18） Accelerate the revision of laws and regulations. Timely summarize the progress of the pilot system for drug listing license holders and the pilot reform of drug registration classification, and promote the acceleration of the revision of the Drug Administration Law of the People's Republic of China. In conjunction with the reform of the administrative approval system, we will promptly revise the Implementation Regulations of the Drug Administration Law of the People's Republic of China and the Drug Registration Management Measures in accordance with the procedures.

（19） Adjust the charging policy. Integrate and merge fee items for drug and medical device registration, approval, and registration. According to the principle of general balance of income and expenditure, the fee standards for drug and medical device registration will be increased and adjusted every five years. Provide appropriate discounts on the registration fees for innovative drugs and medical devices for small and micro enterprises. Fee income is included in the financial budget and managed through two lines of income and expenditure. The funds required for the review and approval work are arranged through the financial budget.

（20） Strengthen the construction of evaluation teams. Reform the employment system of public institutions, recruit technical evaluation talents from society, implement contract management, and implement salary and social security in accordance with relevant national regulations. According to the needs of the review, relevant external experts are invited to participate in the relevant technical review, clarifying their responsibilities and confidentiality responsibilities, as well as systems for avoiding conflicts of interest. Establish a system of chief professional positions, scientifically establish a position system that reflects the characteristics of technical evaluation and inspection, clarify responsibilities, tasks, work standards, and job conditions, and implement employment based on the comprehensive abilities and levels of personnel. Promote the construction of a professional team of drug and medical device inspectors. Improve the performance evaluation system, appropriately widen the income gap based on job responsibilities and work performance, and ensure that technical review and inspection personnel are attracted and retained. List the State Administration of Food and Drug Administration as a pilot unit for government procurement services, and entrust qualified evaluation institutions, universities, and research institutions to participate in technical evaluation work such as medical device and generic drug technology review, clinical trial review, and drug safety evaluation through government procurement services.

（21） Strengthen organizational leadership. The State Administration of Food and Drug Administration, in conjunction with the Central Compilation Office, the Development and Reform Commission, the Ministry of Science and Technology, the Ministry of Industry and Information Technology, the Ministry of Finance, the Ministry of Human Resources and Social Security, the Health and Family Planning Commission, the Bureau of Traditional Chinese Medicine, and the Ministry of Health of the General Logistics Department, should establish an inter ministerial joint meeting system for the review and approval of drug and medical devices, strengthen coordination and guidance on reform work, and promptly study and solve contradictions and problems encountered in the reform, Each region should also strengthen its organizational leadership for reform, and report major situations to the State Council in a timely manner.

the State Council

August 9, 2015

(This matter has been publicly released)