Benchmarking with international standards, highlighting clinical value orientation, and establishing drug life-cycle regulatory coverage. This is what CFDA will do next.

Eliminate the backlog of drug registration applications, promote the consistency evaluation of the quality and efficacy of generic drugs, include a batch of new drugs in priority review and even approve the listing, vigorously promote the establishment of the drug marketing authorization holder system, and improve the transparency of review and approval...

For CFDA, 2017 is undoubtedly a busy year. From the beginning to the end of the year, a series of tasks surrounding the reform of the drug review and approval system, such as improving drug quality, improving the ecology of drug research and development, and accelerating the review and approval of innovative drugs, have all been put on the agenda and launched quickly. In response to previous industry criticisms of delayed efficiency and slow approvals, in 2017 CFDA is re-presenting itself in front of the industry with an image of openness, transparency, and efficiency.

On December 23, CFDA Deputy Commissioner and Party Member Sun Xianze attended the 2017 Beijing Pharmaceutical Annual Conference, and made a long-term contribution under the theme of "Learning and Implementing the Spirit of the 19th National Congress of the Communist Party of China, Deepening the Reform of the Drug Regulatory System, and Encouraging the Innovation and Development of the Pharmaceutical Economy". The 45-minute report gave a detailed introduction to the work done by CFDA in the past year or even longer.

In addition to the deputy director of the CFDA, Sun Xianze also has an identity as the chairman of the Chinese Pharmaceutical Association. "I am very pleased to be able to share with you some personal experience we have learned from the 19th National Congress of the Communist Party of China and the current reform of drug review and approval." At the Beijing Pharmaceutical Annual Conference, Sun Xianze opened the scene with these words.

And then, many heavy news will come one after another. According to the information disclosed by Sun Xianze during the meeting, the Chinese version of the Orange Book has been solicited for comments and will be announced soon.

2017 transcript: speed up!

If the 2017 CFDA is to be selected for a work that has attracted the attention of the industry, it must be the reform of the drug review and approval system. Since the publication of the State Council’s heavyweight document "Opinions on Reforming the Review and Approval System for Drugs and Medical Devices" in August 2015, the "five major reform goals, twelve reform tasks, and four guarantee measures" proposed by the State Council have become CFDA tight The focus of work around.

The change is reflected in the resolution of the backlog of drug registration. "We can announce that the backlog of drug registration applications has been basically resolved. Chemical drugs, vaccine clinical trial applications, and various types of registration applications for traditional Chinese medicine and ethnic medicine have been approved within the time limit." In the meeting, Sun Xianze said so. The data is convincing, and the current number of drug registration applications has been reduced from 252,000 in 2015 to less than 4,000.

The reason why the historical problem of the backlog of drug registration applications can be resolved in such a short period of time is closely related to the large amount of resources and attention the CFDA has invested in this area. The first is the expansion of the drug review and approval team. Sun Xianze revealed that through government purchases of services, the drug review and approval team has increased from less than 200 in 2015 to nearly 1,000 today.

The second is the innovation of communication mechanism. Sun Xianze said that at present, in accordance with the rules of new drug development and evaluation, a mechanism for communication between the indication team and planning applicants has been established, and technical reviews have been carried out in the form of the indication team. "Before it was a window queuing. Now we are queuing separately according to 17 indications, so the review speed is much faster."

The speed of examination and approval of new drugs has increased, and a batch of new drugs have been approved for listing first, which is a direct result of the establishment of a priority review system. According to the requirements, drugs in 17 situations such as the prevention and treatment of AIDS, malignant tumors, major infectious diseases, rare diseases, and children’s drugs should be included in the priority review. Sun Xianze revealed that there are currently 353 drug registration applications included in the priority review Among them, 40 are medicines for children, as well as a batch of global medicines, such as recombinant Ebola vaccine, 13-valent pneumococcal conjugate vaccine, etc., through this method, obtained timely market.

The requirements for improving the quality of drugs represented by the quality of generic drugs and the consistency evaluation of efficacy are also the focus of CFDA's work in 2017. Sun Xianze said that a total of 25 supporting documents for consistency evaluation have been issued, 70 are accepted for consistency evaluation of generic drugs, and there are nearly 6,000 generic drug reference preparations, and the number of BE filings is continuing to increase. 289. It is worth noting that there are varieties that have successfully passed the consistency evaluation work, such as Chia Tai Tianqing’s tenofovir dipivoxil, but at the same time there are also varieties that have clearly been blocked from the consistency evaluation, such as Hisun Pharmaceutical Of tacrolimus capsules.

It is worth noting that according to the information disclosed by Sun Xianze during the meeting, the Chinese version of the "Orange Book" may soon be announced. The Chinese version of the Orange Book refers to the "List of Listed Drugs in China". On September 4 this year, the CFDA Drug Approval Center issued a notice for soliciting opinions on the document framework, which stipulates that drugs that pass the consistency evaluation of quality and efficacy can be used. Be included in this directory. Sun Xianze said that the current solicitation of opinions has ended and will be released soon.

In addition, improving the transparency of review and approval and letting power run under the sun has been the main theme of the CFDA's work in the past year. "We have fully disclosed the standard technical requirements for acceptance, review, and on-site verification of drug registration, and publicized information about acceptance and approval to guide applicants in orderly research and development." This includes the release of monitoring of shortages of drugs and encourages enterprises to declare rationally. , Including some varieties whose patents have expired in the world but have not yet been proposed for imitation in China, "encourage everyone to fill in the gaps in China in time."

Regarding the pilot program of the drug marketing authorization holder system, "definite + expansion" is the keynote. In November 2015, the first MAH system pilot project in ten provinces and cities including Beijing and Shanghai officially started. Sun Xianze revealed that up to now, a total of 560 registration applications have been received. The next step is to broaden the scope. Any enterprise with an approval number can be the holder of a listing license." Sun Xianze said that he is currently applying to the National People's Congress to spread the MAH system across the country. According to the news previously learned by the E drug manager, MAH has been placed in an extremely important position in the amendment to the Drug Administration Law under consideration.

In the past year, the CFDA has made great strides to purify the drug R&D ecosystem, including thorough investigations of the falsification of clinical trial data. "We sent 185 inspection teams to verify drug clinical trial data on 313 drug registration applications. Among them, 35 registration applications were rejected, and 11 clinically-verified units were filed for investigation, including clinical institutions. And CRO."

2018 small goal: benchmarking international

"The problems of unbalanced and inadequate development are very prominent in the field of food and medicine, and can easily become the focus of attention of the people." "Currently, the availability of medicines in my country is basically solved, but there is a gap in quality and efficacy, especially There is a gap between generic drugs and original research drugs." In his speech, Sun Xianze did not shy away from the current significant problems in the food and drug field.

But at the same time, the rapid development of China's pharmaceutical industry cannot be ignored. "Since the major new drug creation project, we have approved 24 Class I new drugs. The central government invested 12.8 billion yuan, but the direct economic benefits were 160 billion yuan." "In 2016, the sales revenue of the pharmaceutical industry above designated size was 2.8 trillion yuan. Renminbi, an increase of nearly 10% year-on-year."

Regardless of whether it is from the State Council’s "Opinions on Reforming the Drug and Medical Device Review and Approval System" in 2015, or the "Opinions on Deepening the Reform of the Review and Approval System and Encouraging Drug and Medical Device Innovation" jointly issued by the Central Office and the State Council in 2017 , The policy support for the pharmaceutical field cannot be clearer. In Sun Xianze's view, there are at least the following characteristics:

1. Comparing with international standards. Regardless of quality standards, review standards or management standards, Chinese new drugs must be fully equated with global new drugs, and generic drugs must be completely consistent with the original drugs in terms of quality and efficacy.

2. Highlight the orientation of clinical value. It is precisely because of this that the current approval mechanism is adjusted to take the clinical department as the lead unit, and pharmacy, pharmacology, and toxicology must all act as its cooperating departments.

3. Clarify that the holder of the drug marketing authorization is the main body responsible for the entire life cycle of the drug.

4. Establish a regulatory system covering the entire industry chain, and strengthen full coverage before, during and after the event.

Specifically, in 2018, at least the reform of drug clinical trial institutions, the continued acceleration of marketing review and approval, the promotion of drug innovation and the development of generic drugs, and the reform of the MAH system will remain the focus of the CFDA's work.

"At present, we have 989,000 hospitals at all levels, but there are only more than 2,000 tertiary hospitals, and only more than 7,000 second-level hospitals. The rest are all township health centers, community health centers, clinics, etc. Among them, through There are only 621 certified clinical institutions, and only more than 100 are able to carry out Phase I clinical trials.” At the meeting, the simple numbers of clinical trial institutions were already shocking.

"To encourage innovation, we must first solve the bottleneck problem of clinical trials." Sun Xianze said that CFDA will further increase clinical resources and carry out a series of reforms, including canceling the qualification certification of clinical trial institutions, changing to filing management, and employing clinical trial sponsors A third party conducts assessment and certification, thereby liberating 2,000 tertiary hospitals and 7,000 secondary hospitals.

"Clinical trial projects are filed on the website of our Drug Evaluation Center, and the original nodding system is changed to the shaking head system." In layman's terms, the original drug evaluation center does not nod and agree, and the clinical trial project cannot be carried out, which is why the clinical trial approval time Long stools have been criticized. Sun Xianze said that after the reform, China's innovative drugs will be launched two to three years earlier than before. "Generic drugs are filed directly. After getting the filing on the same day, you can start experiments immediately after success. Innovative drugs can take 60 working days. As long as I don’t say disagree, you can start them. You can automatically get an approval number and you can start clinical trials. experiment."

In this case, what is emphasized is the enthusiasm of medical staff to participate in clinical trials. “In terms of salary promotion and title promotion of clinical experiment researchers, they must be treated the same as clinicians.” Sun Xianze revealed that this is a consensus that has been reached with the Health and Family Planning Commission.

In terms of drug marketing review and approval, the speed of meeting the requirements in 2018 will be further accelerated. For example, rare disease drugs can be approved for listing with conditions. At the same time, drug raw materials, excipients and packaging materials will also be implemented. Management approval. Support the inheritance and innovation of traditional Chinese medicine, highlight the clinical value-oriented, "review and approve in accordance with simplified standards, rather than exempt from clinical." However, natural medicines still need to be reviewed and approved in accordance with modern medical standards.

In terms of promoting drug innovation and the development of generic drugs, it is necessary to strengthen data protection, to grant a certain period of protection to innovative drugs, data on the safety, effectiveness and other data obtained in clinical new drug experiments, and to explore the establishment of drug patent connections. System to form a combination right to protect intellectual property rights of drugs, while protecting the legal rights of patent rights and stimulating the vitality of innovation, it encourages imitation, guides imitation, and regulates imitation.

The focus of work is to fully implement the marketing authorization holder system and strengthen the management of the entire life cycle of drugs. Timely sum up experience, promote the revision of the Drug Administration Law, and establish a system for marketing authorization holders to directly report adverse reactions and adverse events. If adverse reactions or serious adverse events occur, sales should be suspended in a timely manner according to the situation.