Reform of the examination and approval system for drugs and medical devices： people’s health needs to be reviewed and reformed without stopping.
Medical technicians in Cihu High-tech Zone, Ma ‘anshan City, Anhui Province are developing COVID-19 pharmaceutical core intermediates. Wang Wensheng photo/bright picture
Workers of a pharmaceutical company in Shijiazhuang, Hebei Province work in the pharmaceutical production workshop. Xinhua news agency
[Endeavour, New Journey, New Era, Great Change]
Since the reform of evaluation in 2015, National Medical Products Administration has approved 95 innovative drugs and approved 155 innovative medical devices to be listed.
Five Covid-19 vaccines were approved for conditional marketing, two Covid-19 vaccines were approved for emergency use, and 34 vaccine varieties with five technical routes entered clinical trials.
106 novel coronavirus detection reagents were approved, including 38 nucleic acid detection reagents, 37 antibody detection reagents and 31 antigen detection reagents.
"The quality of registration application materials is not high, and it needs to be supplemented and improved many times during the review process, which seriously affects the efficiency of review and approval; Repeated construction and application of generic drugs, vicious competition in the market, and the quality of some generic drugs is far from the international advanced level; The listing approval time of new drugs urgently needed in clinic is too long, and drug research and development institutions and researchers cannot apply for drug registration, which affects the enthusiasm of drug innovation. "
This is a frank and incisive analysis of drugs and medical devices related to people’s lives and health in a the State Council document seven years ago. This analysis resonates with the confusion of the people: Why are some drugs "slower" to market in China than in foreign countries? Why do some people go overseas to purchase medicines?
The full name of the the State Council document is Opinions on Reforming the Examination and Approval System of Medicines and Medical Devices, which was issued in August 2015, thus kicking off the reform of the examination and approval system of medicines and medical devices in China (hereinafter referred to as the examination and approval reform). Especially since its establishment in 2018, National Medical Products Administration has continuously deepened the reform of evaluation, encouraged the innovation of drugs and medical devices, improved the quality of drugs and medical devices, increased effective supply, and effectively guaranteed people’s health and life safety.
1. The backlog of registration applications has been solved.
The quality of drugs and medical devices is related to everyone’s health and safety, which is the original intention of implementing the review and approval system. However, if the evaluation efficiency is too low, it will lead to the lag of product listing time, which will also affect people’s health and safety. After all, disease waits for no one.
Take drugs as an example. In the past, the backlog of drug registration applications in China was serious, with a maximum of 22,000 applications. Many drugs have to wait several years for approval after they apply for registration. Pharmaceutical companies are helpless and patients are miserable.
How to speed up the review? This is the first problem to be solved in the reform. The drug regulatory authorities, seeing the move, launched a series of powerful measures — —
Full implementation of the implied license system for 60-day expiration of drug clinical trials, which is one-third shorter than the 90-day review time limit before the reform.
We will establish and improve the procedures for accelerating the listing and registration of drugs, optimize the review and approval process, and give priority to the clinical shortage of drugs, anticancer drugs, drugs for children, drugs for rare diseases, drugs for major infectious diseases, vaccines urgently needed for disease prevention and control, and innovative high-end medical devices, thus greatly shortening the review time limit.
Drugs that show efficacy in early clinical trials can be conditionally approved for marketing and used in urgent need patients who can’t wait any longer.
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As a drug technical evaluation institution, National Medical Products Administration Drug Evaluation Center has also strengthened the management of evaluation items, refined the evaluation sequence, strengthened the management of time limit, set up special groups, increased reviewers, revised the evaluation points, standardized technical requirements, etc., and the evaluation standards, quality and efficiency of drugs have been greatly improved.
"From the peak in 2015, there was a backlog of more than 20,000 applications. By 2018, more than 90% of them were reviewed within the time limit, and China’s drug review and approval entered the fast lane." The relevant person in charge of the Department of Drug Registration of National Medical Products Administration told the reporter that, for example, in terms of new drugs urgently needed overseas, by the end of 2021, 51 new drugs urgently needed overseas were approved for listing, among which the review of rare diseases drugs was completed within 3 months, and the review of other drugs urgently needed clinically was completed within 6 months, which greatly shortened the time for listing new drugs urgently needed overseas in China.
2. The innovation enthusiasm of the pharmaceutical industry has been stimulated.
The backlog of applications has been solved, and the speed of drug listing has been accelerated. However, in order to meet the people’s drug demand, new drugs need to be put on the market continuously. Encouraging drug innovation is the core of evaluation reform.
In 2015, the Opinions on Reforming the Examination and Approval System of Drugs and Medical Devices raised the standards for drug approval, and changed the new drugs from "drugs that were not marketed in China" to "drugs that were not marketed in China or abroad", that is, "global new". Two years later, the General Offices of the General Office of the Central Committee of the CPC and the State Council issued the Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, and made special arrangements for the innovation of pharmaceutical and medical devices.
The reporter learned that in order to encourage the research and development of innovative drugs and medical devices, National Medical Products Administration not only gave support in priority evaluation, but also formulated a series of technical guiding principles, such as "Technical Requirements for Application for Pharmaceutical Common Problems in Phase I Clinical Trials of Innovative Chemicals", to guide the application for research and development of innovative products. Reviewers will also take the initiative to communicate with R&D producers in key review links such as pre-clinical, clinical and pre-listing, so as to avoid detours.
"The review reform encourages clinical value-oriented drug innovation, optimizes the review and approval procedures for innovative drugs, and accelerates the review of innovative drugs that are urgently needed in clinic, which greatly stimulates the research and development vitality of pharmaceutical companies." The relevant person in charge of Renfu Pharmaceutical Group Co., Ltd. told reporters that in recent years, a number of new drugs have been approved for listing in this enterprise, and new breakthroughs have been achieved in innovation capability.
Among many reform measures, the system of drug marketing license holders deserves attention. Previously, only pharmaceutical manufacturers could apply for drug registration. In order to register drugs, researchers and research institutions must first invest and build factories themselves. This management system of product registration and production license is not conducive to drug innovation. In 2015, China launched a pilot system of drug marketing license holders in 10 provinces and cities, and drug research and development institutions and researchers can apply for registered drugs. Expert analysis pointed out that this move reduced the capital investment and time cost of drug developers, and new drugs could be listed three to five years in advance. In 2019, the drug marketing license holder system was written into the newly revised drug administration law and was fully implemented nationwide.
According to National Medical Products Administration, in recent years, China has made great progress in the development of innovative drugs. From 2018 to 2021, the number of innovative drugs approved for marketing increased year by year, with 11, 12, 20 and 45, respectively, including Covid-19 vaccines and clinically urgent therapeutic drugs in the fields of tumors, immune system diseases and rare diseases. The pace of medical device innovation is also accelerating. In 2021, 35 innovative medical devices were approved for listing, which is the largest number of innovative products approved in recent years.
3. Consistency evaluation improves the efficacy of generic drugs.
In recent years, many drugs that were originally expensive began to reduce their prices. Careful observation shows that there is a "hero" behind the decline in drug prices — — Generic drugs.
Innovative drugs provide new options for treating diseases and saving lives, but for the vast majority of patients, generic drugs are their life. According to National Medical Products Administration, China’s modern pharmaceutical industry started late, and the production of drugs is mainly imitation. More than 95% of the chemicals that have been approved for marketing are generic drugs.
Generic drugs are imitations of the original drug after the patent protection period expires, and the price is much lower than that of the original drug. In the past, China’s generic drug evaluation and approval standards were not high, and there was a lack of high-quality generic drugs, and the curative effect was very different from that of the original drug.
Improving the quality and efficacy of generic drugs is an important goal of evaluation reform, and the solution is the consistency evaluation of generic drug quality and efficacy — — For generic drugs that have been approved for marketing, the evaluation should be carried out according to the principle of consistency with the quality and efficacy of the original drug. The core is that generic drugs should reach the level consistent with the original drug in quality and efficacy, and can replace the original drug in clinic.
"There are several key issues in carrying out consistency evaluation, one is the selection and determination of reference preparations, the other is the determination of technical standards, and the third is to strictly follow the procedures." According to the person in charge of National Medical Products Administration, the Bureau ensured the smooth development of generic drug conformity evaluation by improving the evaluation system, strictly evaluating standards, strengthening service guidance and optimizing the workflow. At present, 4677 specifications of generic reference preparations have been published, and 2044 specifications and 437 varieties have been applied for through consistency evaluation.
Consistency evaluation puts generic drugs on the right track, and ultimately benefits the people. Since the pilot of centralized drug procurement and use organized by the state was launched nationwide in 2019, a number of domestic generic drugs won the bid. Medical insurance, health insurance and other departments have organized medical institutions to carry out research on 14 representative generic drugs that won the bid, and confirmed that these 14 generic drugs that passed the consistency evaluation are clinically equivalent to the original drugs. Generic drugs with the same efficacy as the original drug are not only cheaper, but also further reduce the price of the original drug under competitive pressure, greatly reducing the burden of patients.
4, emergency review and approval for epidemic prevention and control to provide a strong guarantee.
4 days, which is the time for China to complete the review and approval of the first Covid-19 nucleic acid detection reagent and sequencing reagent in the world.
On January 20, 2020, National Medical Products Administration Instrument Center started the emergency work overnight, and the reviewers stayed up all night to connect with the enterprises one by one, and the review and research and development were carried out simultaneously. On January 26th, the first batch of four in vitro diagnostic reagent products were approved for marketing, which provided an effective detection method for the first line of anti-epidemic.
The outbreak of epidemic situation in COVID-19 challenges the evaluation reform. Xu Jinghe, deputy director of National Medical Products Administration, said at the Boao Forum for Asia in 2021 that the role of drug supervision departments in epidemic prevention and control has changed, from reviewers to instructors, working with enterprises to speed up product listing.
It is understood that National Medical Products Administration made every effort to carry out emergency review and approval during the epidemic. Five Covid-19 vaccines have been approved for conditional marketing, two Covid-19 vaccines have been approved for emergency use, and 34 vaccine varieties from five technical routes have entered clinical trials. Organized the formulation of three technical guidelines for research and development of therapeutic drugs in Covid-19, approved 58 applications for clinical trials of therapeutic drugs in Covid-19, and approved the registration and listing of Qingfei Detoxification Granules, Huashi Detoxification Granules and Xuanfei Detoxification Granules. 106 novel coronavirus detection reagents were approved to effectively meet the needs of epidemic prevention and control.
The epidemic is not over yet, and the emergency review and approval is still going on. As long as people’s health needs it, the evaluation reform will not stop. The drug supervision departments and reviewers have been speeding up on the road of realizing healthy China, so as to run out of acceleration for people’s health.
(Reporter Chen Haibo)