Thousands of clinical research sites get together and three major paths help global simultaneous R&D registration and review

Recently, PhIRDA and RDPAC jointly released the "Part Four: Promoting the Simultaneous R&D, Registration and Evaluation of Innovative Drugs" report.

Since China joined the ICH (International Technical Coordination Committee for Drug Registration for Human Use) in 2017, it has fully introduced the globally accepted technical requirements for drug R&D and registration.

Clinical trial approval time was once a link that severely restricted the speed of new drug approval.

The significant improvement in the time for the approval of innovative drug clinical research and registration and marketing applications has resulted in a significant increase in the number of innovative drugs (including Class 1 innovative drugs and overseas original research drugs) approved in China in recent years, which has approached the level of developed countries and regions

But we still need to see the gap behind it

Nearly 30 overseas-produced original research drugs approved for listing in China for the first time in 2020 (not including re-registration, the listing of generic drugs in China before the approval of the original research, and the new indications for the same product), the time when the same product was approved in China The first approval time in other markets around the world is 3.

The reason for the gap is that, on the one hand, the results of China's accelerated reform of review and approval have not yet fully appeared in the drugs approved in 2020, and on the other hand, because China has not yet fully joined the global simultaneous research and development

While China's participation in global simultaneous R&D registration has achieved results, it also faces many challenges

How to vigorously promote simultaneous R&D, registration and review? There are three potential paths:

Path 1: Based on the concept of ICH E17, innovative drug R&D companies include China in the early clinical trials of drug global R&D, and communicate with the Chinese drug regulatory authorities on key issues and links in the new drug R&D process as early as possible to achieve clinical trials.

Path 2: Based on the concept of ICH E17, innovative drug R&D companies will include China in the confirmatory clinical trials in the middle and late stages of drug global R&D to ensure that sufficient data are obtained (including extension of China’s enrollment time if necessary), and to support synchronization in China Register for listing;

Path 3: When China is unable to participate in international multi-center clinical trials, it plans to register and go public in China as early as possible

Based on the combing of the three potential synchronization paths, improving the scientificity of registration supervision and the efficiency of clinical research is the key to vigorously promoting synchronization

01 Improve the scientific nature of registration supervision

The current challenges to the scientific nature of registration supervision are mainly reflected in the three directions of "scientificity of regulatory policies", "scientificity of regulatory standards and procedures" and "scientificity of regulatory systems"

First, the scientificity and transparency of the approval of the Genetics Office, and the gap between the actual implementation of the marketing authorization holder system and the system design are the pain points of the scientific nature of the current regulatory policy

On the other hand, there are still certain challenges in the full implementation of the listing permission holder (MAH) system at this stage, which are mainly reflected in the obstacles to the implementation of the cross-border MAH and the ability of the license holders of the affiliated institutions of the group company.

Take biological products as an example.

Second, the full implementation of ICH E17, review procedures, registration data requirements, four registrations to support innovation, and speeding up the construction of channel rules are all scientific challenges to regulatory standards and procedures

Third, as the drug reform gradually enters the deep water zone, a scientific, high-quality, and sustainable drug regulatory system has become a more long-term strategic goal in the current comprehensive deepening of the reform process
.
However, with the introduction of policies to encourage innovation, a large number of "swarm" developments of products with no obvious differences have appeared in some fields, and the phenomenon of homogeneity has become serious
.
This not only takes up valuable clinical resources, but also limits the improvement of clinical research and development capabilities
.

02 Improve the efficiency of clinical research

Driven by the policy of encouraging pharmaceutical innovation, the number of clinical trials in China has rapidly increased: In 2019, the number of drug clinical trials in China exceeded 1,600, which is more than 20 times more than the number of clinical trials with less than 100 a decade ago
.

At the same time, the number of clinical research institutions in China has also grown steadily in the past five years, from less than 400 in 2015 to more than 1,000 in 2020, which to a certain extent has undertaken the growing demand for clinical research
.
However, the lack of experience of most institutions has led to the fact that the sponsors gather in the head research sites.
In the past two years, less than 30% of institutions have undertaken more than 20 clinical studies; the experience of undertaking international multi-center clinical trials is even more lacking, with only 6% domestic The institution undertakes more than 20 international multi-center clinical trials
.

Studies have shown that to improve the efficiency of clinical research, it is necessary to start with both clinical program execution and clinical research capabilities
.
On the one hand, optimizing the intra-institutional process and inter-institutional coordination in the execution of clinical research, promoting the simplification of the ethical approval process, and improving the efficiency and level of regional or central ethics
.

On the other hand, promote the establishment of a professional clinical research platform and the construction of a full-time clinical research team, and promote a clear positioning of the institution.
Leading research institutions can focus more resources on projects with a higher degree of innovation
.
At the same time, increase investment in clinical research resources
.
According to the data, among the medical science projects approved by the National Natural Science Foundation of China in 2019, there are only 94 clinical medical research related projects, accounting for less than 1.
0%; the total fund approved for funding is 47.
331 million yuan, accounting for the National Natural Science Foundation of the year.
0.
2% of the total, with an average of only about RMB 500,000 per item, there is an order of magnitude difference in clinical research costs in the same industry
.

03 Strengthen supervision and clinical capacity building

In the process of advancing the global simultaneous research and development, registration and review of drugs, the current capacity training of supervisory reviewers and the construction of talent echelons may become new bottlenecks that are not compatible with the rapid development of innovative drugs and clinical treatment needs
.

Although the number of personnel in the Center for Drug Evaluation (CDE) has increased significantly in the past five years, high-level review personnel are very scarce, and are still unable to fully meet the ever-increasing demand for applications, especially biopharmaceutical review experts and clinicians.
The demand for review experts exceeds demand
.

According to the calculation of the full-time workload of the review team in the United States, the actual number of review personnel required by the China Drug Administration is about 3,000, but only about 700
.

On the other hand, with the rapid development of the industry, the original knowledge system of the review agency staff cannot cover new scientific mechanisms and advanced technological breakthroughs
.
At present, the development stage of drug review and approval departments in developed countries and regions is relatively mature, and the setting of relevant sub-departments is also more specialized and detailed
.
Taking the FDA as an example, it has 12 sub-departments including the Drug Evaluation and Research Center, the Biological Product Evaluation and Research Center, and the Regulatory Affairs Office
.
Among them, the Drug Evaluation and Research Center, which is most relevant to drug review and approval, has 12 departments including the New Drug Office, the Generic Drug Office, and the Drug Quality Office
.
The Office of New Drugs has further refined 11 offices and 28 departments under the office according to disease fields and functions
.

However, it must be recognized that the cultivation of the ability of the supervisory team is a long-term and gradual process, which requires corresponding institutional guarantees, and provides a career path and a systematic ability to advance platform
.
The survey shows that the current domestic regulatory talent source background is relatively single, which can promote the increase of multi-directional talent flow between regulatory agencies, academia and sponsors, and enrich the source of regulatory talent to a greater extent
.

Third, internationalization will become the focus of the development of innovative drugs in the next ten years.
Therefore, the ability to promote international exchanges in the practice of regulatory modernization is important
.
In the past three years, in order to further promote the globalization process and review efficiency of new drug approvals, the FDA has launched many new measures, such as the Orbis program to promote cooperation between cross-regional regulatory agencies and the real-time review of oncology innovative drugs.
Deepening reform has important reference significance
.

Fourth, the construction of a digital tool platform can promote the quality and efficiency of research in many aspects of clinical research
.
It can promote the digital management of the whole life cycle, and promote the digital upgrading of supervision and industry
.