SINO-EUROPE SYMPOSIUM ON TRADITIONAL CHINESE MEDICINE & HERBAL MEDICINE-MARKET OVERVIEW ®ULATION POLICY

Regulation Progress of Traditional Medicines in China

Wang Hainan (王海南)

(Director, Division of Traditional Chinese Medicines and Ethno-Medicines, Department of Drug Registration, National Medical Products Administration, China)

Let me introduce Chinese medicines. I will speak in Chinese, and I will express myself more clearly.

Just now I listened carefully to Professor Werner Knoess, the doctor's report, giving me a deep feeling.As long as it is the medicine, modern or traditional, the general requirements to conform with, are the same,namely, safe, efficient and quality control. We cannot say that because these are traditional medicines, there is a special evaluation of a set of so-called emphasis on the featured theory, especially in the evaluation of efficacy. This is not often the case in China. Sometimes industries, and experts often criticize our supervisory authorities for supervising Chinese medicine with a set of western medicine rules. Actually, I feel that there is a big misunderstanding here. The reason why I see the term used in Sino-European communication today is traditional medicine, I have been thinking about what the connoation of the traditional medicines is. I am fully convinced that tradition does not mean backwardness. The reason why traditional medicine is called traditional medicine is that it is different from western, modern or contemporary medicine in terms of theory and paradigm it follows.However, traditional medicines actually incorporate modern development concepts. I think traditional medicine can't be understood simply from time, as if Chinese medicine with hundred years or thousands of years history were called traditional medicine. But traditional medicine in the 21stcentury is not traditional medicine. To be classified into the traditional medicine category, the most important thing is to look at the concepts and modes that it follows.

We once discussed the mode of traditional medicine supervision. some experts said whether in the future, our Chinese medicine should be divided into socalled tradition and modernity, but some have different opinions on that, and even opposed it. I think the reason for objection that it is difficult to separate the tradition from modernity, so there is a saying in our Medicine Administration Law that the state supports the development of modern medicine and traditional medicine. We think that the Chinese medicine should be included into traditional medicines. But we must understand traditional medicine,which can not only be limited to the era when it was born.Modern exists in tradition.

Today, based on these ideas, I will talk about our China's supervision of Chinese medicine.

Everyone knows that in 2018, our country has undergone institutional adjustments. The Chinese medicine regulatory authority was originally in China Food and Drug Administration. After 2018, they were called Drug Administration under the State Administration of Market Supervision. The name has also changed from CFDA to NMPA, which is our current management body. Of course, in China, the management of traditional Chinese medicine actually implements in the national system. In addition to State Medical Production Administration, the departments taking part in Chinese medicine management also include National Administration of Traditional Chinese Medicine, Ministry of Commerce, Ministry of Science and Technology,Ministry of Industry and Information Technology etc.Therefore, in China; it is actually a national system to jointly manage Chinese medicines. Our National Medical Products Administration (NMPA) is mainly responsible for the registration, production, circulation and use of products. That is the main responsibility of NMPA.

In fact, I just talked about it at the beginning. Why do we say that the actual scope of Chinese medicine is a traditional medicine? We follow the concept of traditional medicines. Its general realma and method, and phamacy method are different from those of modern medical theory. For example, in our concept. The main core idea of TCM theory is to emphasize the holistic view, and dialectical treatment, rather than simply saying that a single indication is used to guide clinical use of medicines like modern medicine. Generally speaking, traditional Chinese medicine we talk about refers to the medicinal materials and their preparations used for the prevention of diseases under the guidance of the theory of traditional Chinese medicine. It is divided into three categories:Chiese medicinal materials, Chinese medicine decoction pieces and Chinese patent medicines. Therefore, in China,pieces the Chinese medicine industries are divided into three categories: Chiese medicinal materials industry,Chinese medicine decoction pieces industry and Chinese patent medicine industry.

Chiese medicinal materials include three major categories, including plants, animal and minerals. After the initial processing of the raw materials, they are used for decoction pieces and patent Chinese medicines.

Chinese herbal medicine, mainly different from the crude medicines, need processing, with one or two thousand years of experience. Therefore, Chinese medicine decoction refers to prescription medicines that can be directly used in clinical traditional Chinese medicine or in the production of preparations after being processed. In China, if a Chinese medicine practitioner's a prescription contains multi-flavored Chinese medicine decoction, the patient will boil it in his/her home, using Tang from it. Such was the Chinese herbal medicine used in clinical practice. In addition, as for Chinese patent medicines, we require that decoction will be made into preparations.

Decoction pieces processing is an important feature of traditional Chinese medicine. This is probably only China has such a thing in the world, because in Europe,and Japan, their Chinese medicine is basically not processed. They mainly use crude drugs, and some use grinding powder. Decoction processing is a good way to practice Chinese medicine theory, reflecting the essence of Chinese medicine culture. It is a very obvious difference between Chinese medicine and EU herbal medicine and natural medicine in other countries. Here, the purpose of processing is to increase efficiency and reduce toxicity,and to help active ingredients to be decocted.

Chinese patent medicine, which combine the active ingredients of traditional Chinese medicine decoction and effective constitute from extracts derived from natural products, according to the theory of traditional Chinese medicine, are the processed pharmaceutical preparations according to the fixed prescription.

This slide shows the relationship between Chiese medicinal materials, Chinese medicine decoction and Chinese patent medicine.

Chiese medicinal materials are the raw materials of traditional Chinese medicine decoctions and Chinese patent medicine. Chinese medicine decoctions are also the raw materials Chinese traditional medicine from the perspective of Chinese patent medicine. Those are the relationship of the three. Chiese medicinal materials must be processed before they can become decoctions. The decoction pieces, as the raw material, are prepared into Chinese patent medicines, which can also be directly used in clinical practice.

I just spent a little time telling you how to come to know and understand Chinese medicine in China. What is its connotation?

I have already said that the departments related to NMPA and Chinese medicine supervision after the reform is now mainly two departments. One is medicine registration department and the other is medicine control department. Medicine registration department is mainly responsible for medicine market access and medicine standard formulation while medicine supervison department is mainly responsible for the supervision of medicine production and circulation, etc. In the medicine registration department, we have formulated GCP and GRP regulations while the medicine supervision department is mainly GMP, GSP, etc., which is organized to formulized in that department.

Additionally, National Family and Health Planning Commission (NFHPC), National Medicare Security Administration(NMSA),Ministry of Science and Technology (MST), Ministry of Commerce (MOFCOM),and National Administration of Traditional Chinese Medicine (NATCM) all play management role in combining Chinese medicine with their respective functions.

That is our legal framework system, which is generally divided into laws, regulations, regulatory and technical documents, and guiding principles. I feel that that is a certain degree corresponding with the EU system. I also feel that they are a bit close to the guiding principles.

However, in the traditional medicine management,we must also follow the quality control of safety and efficacy, and follow the GCP, GRP, GMP, GSP and other regulations.

From legal perspective, we must now manage Chinese medicine, according to two laws. One is Law on Medicine Management the People's Republic of China, and the other is Law on Chinese Medicine of the People's Republic of China, which elaborate on management method of Chinese medicine in China.From the administrative regulations of the State Council, we also have the Regulations on the Implementation of the Law on Medicine Management of the People's Republic of China and a Regulation on the Protection of Chinese Medicine Varieties, which are issued by the State Council.

Focusing on the management of the whole life cycle of medicines, we have also issued regulations on the management of medicine registration, medicine labeling and label management, and other departmental regulations on imported medicine. Additionally, we have issued a lot of regualtions such as GAP, GLP, GCP, GMP etc.

In order to strengthen the management of medicine registration, we have also specially formulated and issued the regulatory provisions on the registration of Chinese medicine, as complemetation, by fully taking into account the characteristics of traditional Chinese medicine and its development rules. At present, we have formulated and published guidelines for the registration of more than 40 Chinese patent medicines. Unfortunately, these guidelines are published in Chinese. I have always been suggesting to organizations including our pharmacopoeia commission, International Exchange Center etc. All of them should be translated into English and linked to the website. We have some ideas on management and experience, which could be shared with management departments of phytomedicine or traditional medicines.

Our guiding principles are also divided into the quality control of pharmacy, toxicological research on safety, preclinical and a large number of technical guidelines based on clinical research. That is mainly an enumeration, not all.

Technical guidelines of pharmaceutics include the handling of raw materials, extraction, and purifications,including post-marketing process changes. In terms of preclinical toxicology, In terms of preclinical toxicology,we have guiding principal for safety pharmacology,for toxicity of single administration, for repeated administration, for immunotoxicity and reproductive toxicity.

It should be said that a relatively complete system of technical guiding principle, has been constructed in our country. Of course, this technical guiding principle needs to be continuously enriched and improved in supervision and practice.

I have already said that we are supervising Chinese medicine. Now NMPA is based on the management of the whole life cycle. Before the listing, after the listing, there are relevant departments and clear policies to manage Chinese medicine.

That is actually a departmental framework of NMPA, which mainly focuses on the formualtion of macro policies. The specific technical level of implementation is supported by the following technical departments, such as National Institute for Food and Drug (NIFD), National Pharmacopoeia Commission,Center for Medicine Evaluation, NMPA, Center for Inspection, NMPA, and Center for Assessment, NMPA,etc. Pre-marketing supervision is mainly done by the drug registration department, including a series of premarketing regulations, which I have already introduced.

The listing of new Chinese medicine is in two major ways in our country. One is a complete registration procedure from pre-clinical to clinical trials and approval for marketing. Good data on clinical trials should be provided before listing to guarantee the data of clinical trial. And non-clinical safety study should be conducted very adequately.

Since last year, we have introduced this simplified registration process. Of course, when we made it, we did refer to some of the EU's ideas and practices.

Of course, our simplification is obviously different from that of the EU, and ours are from the Qing Dynasty,which have a long history, and the exact clinical efficacy.This efficacy is mainly based on the consensus of experts of Chinese medicine, and the ancient classics that are still widely used. The prescriptions cannot be recognized by 30 or 15 years of usage. And those that can take this simplified registration procedure, must be before the Qing Dynasty, and now is still in use in clinical practice,with recognized efficacy. The catalogue is formulated by National Administration of Traditional Chinese Medicine.

The first batch of catalogue was issued last year.It is possible to have a qualification to go through the simplified registration process with the 100 prescriptions.This simplified registration procedure, does not mean to lower the technical requirements, but rather its safety and efficacy have long been providing clinical evidence of practice. We have repeatedly been stressing that simplification does not mean a reduction of standards,but a reasonable reduction of the application materials.This simplification is mainly free of clinical trials, no need to submit clinical trial data, and no need to provide data of medical researches. However, strict quality control of pharmacy is a very strict requirement, because it does not mean that a well-known prescription, or a prescription written on an ancient book, can become a curative product.It must be different. Quality control, the whole process,strict quality control from beginning to end, GAP, GMP,etc., can ensure that the classic prescription could become a classic product, and we propose that the concept that we should inherit the classics with fine products.

Of course, there is a clear distinction with the EU.There is no strict distinction and indications of Chinese medicine indications. Participation of Chinese medicine in the prevention and treatment of major diseases,such as cancer, tumor, and some infectious diseases,including diabetes, etc. are encouraged, however, as for the understanding of Chinese medicine, of course,we also should understand why the EU should limit the indications of traditional phytomedicine. For tumors, diabetes, etc., it may not be generated. From the perspective of individual use, we have different perspective in China. We emphasize the equal status and integration of Chinese and western medicine. In the whole clinical path, what kind of role can Chinese medicine play in the context of our use of western medicine? We may consider the clinical use of traditional Chinese medicine from more perspectives. We have never restricted China for indications. Instead, traditional medicines are encouraged to actively participate in the prevention and treatment of major diseases. Moreover, we also have developed and used some good medicines in the field of tumor-assisted medicines. As for liver disease, China is also a big country of liver disease. As for the treatment of liver disease, good medicines for anti-liver fibrosis treatment, liver protection, and fatty liver treatment, have been developed and approved of marketing.

Therefore, this slide once again confirms what I have said in the beginning of the lecture. Although our Chinese medicine has been learning from many concepts of modern development in the current development process, it is still in the category of traditional medicines,as it must follow the theory of traditional Chinese medicine. If it does not follow the theory of traditional Chinese medicine, it will not be called traditional Chinese medicine. There is another kind called natural medicine in China, which does not need to follow the theory of traditional Chinese medicine. Instead it completely develops according to the concept of modern medicine.Of course, quality control of the medicine is similar to that traditional Chinese medicine.

The second is that we have a very important concept that emphasizes clinical value-oriented. It is only medicines of clinical value that we are encouraged to develop.Additionally, we emphasize the control of the whole process and the source management, as we also learn the management experience from Chinese medicine in Japan.The management of Chinese medicine is leant from the good practices of the world, which we adopt and use.

Another one we carry out resource assessment,because this is also the characteristics of phytomedicine,which is reliable on resources. Without resources, there could be no sustainable development of the products.From 2017, the introduction of resource assessment, is to require each enterprise to tell the supervisory department about their products. Where are their resources from and where they are used? From a big perspective, it is material balance. It does not to say that this resource assessment is to do a resource survey. Every enterprise clearly understand where the resources are from, and where to use them, so that it is easy to be supervised.When the assessment system are used to check, it is easy to find the problems of some unfaithful companies using unqualified raw materials. On the one hand, resource assessment can ensure the sustainable usage of resources,and on the other hand, it is a policy measure that is very meaningful for strengthening supervision and establishing a traceability system.

Finally, I will talk about the exchange and communication of Chinese medicine.

It should be said that NPMA has always attached great importance to international cooperation and exchanges. We actively participated in the exchange and cooperation in Herbal Forum and Western Pacific Herbal Forum, organized by World Health Organization. We are also very happy to share our experience, because everyone in the world knows that the markets of phytomedicine in the world are of China, the EU and the United States. We are very happy to share each other's experiences. Both Dr.Werner and I are old friends and listen each other's voices in many exchanges. In the Western Pacific Herbal Forum,under the WHO framework, we annually introduce some of our progress in the supervision of Chinese medicine.We are also very pleased that some of our practices have also attracted the interest of many countries around the world, including the Western Pacific Region. They say they are willing to come to exchange views and learn from us. The only obstacle we have now is the language problem. Many of our materials have not yet been translated into English. Then we really have to think of ways to let us break through the language barriers and to let the world share our things as soon as possible. That will accelerate China's TCM supervision going out to the world. And it is conducive to promoting our Chinese medicine products to go for international registration.

If the EU sees the Chinese government's strict management of these products, you can accept these ideas. In fact, this can be discussed to some extent. How to promote Chinese products to register in the EU? I think there will be a long way to go.

FHH is mainly in 6 countries and regions in the Western Pacific Region, as China is major initiator of FHH and IRCH (International Regulatory Cooperation for Herbal Medicines).

In China, we adhere to both Chinese and the Western medicine, Chinese medicine plays an important role in the protection of national health. Chinese medicine enjoys a mainstream status in China and it is also a very obvious different in the world. It is not in a complementary position. Instead it enjoys a high legal status in China like chemical medicines. After two or three decades of hard work, China has established the complete regulatory system with Chinese medicine characteristics. We are willing to share our management ideas in the world.Meanwhile we have been constantly absorbing the good experience of EU, the United States and Japan, to enrich and constantly improve our regulatory system. The regulation of traditional medicines is still promising, as it is with the traditional medicine industry. Let us work together. Thank you all.