Written on 2010/04/07 by Mao Donglei

In the new drug evaluation work, the word “New” is not merely based in the traditional sense such as the meaning of “New” in new compound, new composition, new process and new dosage form, etc., but should also in pursuance for “new curative effect”. Different from the past research and development approach of paying attention to the drug only and ignoring the clinical causes, the new drug evaluation will focus on the actual functions of drugs.

“When compared with the countries having developed pharmaceutical technologies, China has a certain gap in respect of drug research and development, especially drug innovation. One of the important causes is that the insufficient funds contributed for research and development directly affect the enhancement of the capability and innovation level of new drug research and development.”

“At present, an important cause for the difficulty of some new drugs of Class I on market to be in a large scale is that their clinical medical value is ignored.”

“We hope that the past situation that the research on chemical drug innovations only focused on structural innovation but ignored clinical value could be changed.”

“If we could exert the political advantages of China and speed up the establishment and implementation of effective policy advantages, China will undoubtedly take an early step in the development ofnew drug technologies and importing funds.”

“China is ready” should not be a simple slogan, but the actions should be taken.

“Besides that the drug administrative authority should pay attention to the time limit for its own evaluation, the pharmaceutical enterprises should also inspect their internal procedures to find out to what extent the extension of the time for evaluation is caused by themselves.”

In recent years, more and more trans-national pharmaceutical enterprises set up their research and development centers in China and participated in global synchronous development of medicines. What kind of opportunities and challenges do they bring for the evaluation of Chinese new drugs? How should Chinese evaluators appraise their own capability and level of evaluating and approving new drugs? The other day, the reporter of Medical Economic News exclusively interviewed Zhang Wei, director general of the Department of Drug Registration of the State Food and Drug Administration. Zhang expatiated in details around the key stage, global synchronous development and evaluation time limit of the exploration process of creating new drugs, and sorted out the changes of Chinese drug registration standards, laws, regulations and ideologies of recent years.

Reporter: Mao Donglei

Guest: Zhang Wei, director general of the Department of Drug Registration of the State Food and Drug Administration

Changing the Past Situation of Only Paying Attention to Structural Innovations

Q: Hello, Mr. Zhang. In the recent dozen of years, China’s drug research propelled the domestic pharmaceutical industry to change from imitation toward independent innovation, and certain social effects were achieved. A batch of independent innovative drugs has been on market. What kind of advantageous factors do you think that China has already had for research and development innovations?

Zhang Wei: It is a State policy of China to promote the development of innovative drugs. The globalization of drug research propelled China’s drug research and development to change from imitation toward independent innovation. China’s research and development of new drugs have the advantages in the following five aspects: Firstly, the government pays increasingly high attention to medical innovations. Secondly, great progresses were made in protecting pharmaceutical patent. Thirdly, the infrastructures of the medical industry are sound. Fourthly, the work division and cooperation in the medical industry are improving day by day. Fifthly, there are abundant and sufficient human resources and clinical resources. A medical innovation system with products as the core and in the form of industry-university-research cooperation, which is propelled by the government, mainly composed of enterprises, supported by technological institutes, and guided by market is being formed in China.

However, when compared with the countries having developed pharmaceutical technologies, China has a certain gap in respect of drug research and development, especially drug innovation. An important cause is that the insufficient funds contributed for research and development directly affected the enhancement of the capability and innovation level of new drug research and development.

Q: With the promulgation of various innovation encouraging policies, Chinese pharmaceutical enterprises are facing unprecedented opportunities for independent innovations, and the gap from pharmaceutical companies of developed countries needs to be shortened as soon as possible, so as to enable innovation to be a driving force of industrial development. To the drug administrative authority, which improvement measures were taken in recent years to encourage innovations?

Zhang Wei: In respect of amendment of regulations, on October 1, 2007, the SFDA promulgated the newly amended “Regulations on Administration of Pharmaceutical Registration” for implementation. The said “Regulations” were amended mainly in compliance with the following three principles: the first is to encourage drug innovations and lead the research and development of China’s generic drugs, so as to restrain low-level redundant declarations and to focus on raising the threshold for declarations by technical means; the second is to focus on settling the unsatisfied medical demands and to aim at realizing clinical values and advantages; the third is to actively build up a just, transparent and high-efficiency evaluation system, to intensify the division of evaluation duties and the restriction on powers, to reasonably allocate evaluation resources, to improve the evaluation mechanism and procedures, and to realize publicity and transparency to the maximum extent.

Moreover, on the basis of the current research and development situation of China’s drug innovation, we promulgated the “Administrative Provisions on Special Approval of New Drug Registration”, hoping to change the past situation of only paying attention to structural innovations but ignoring clinical values when researching the innovation of chemical drugs. At present, an important cause for the difficulty of some new drugs of Class I on market to make a large scale is that their clinical medical value is ignored. In addition, itis risk in the process of new drugs clinical trial, and such risks cannot be eliminated completely by evaluation, but mainly by the implementation of risk management plans of the enterprises.

In respect of supporting and encouraging global drug research and development, we also promulgated some specific improvement measures. For example, we shortened the time for technical evaluation of the new drugs in clinical application by 25%. We also accepted the international ICH-CTD format for declaration to offer more flexible requirements for submission of cGMP certificates, and simplified the procedures for pre-clinical-trial inspection and review of imported drugs.

“Pharmaceutical enterprises, especially transnational pharmaceutical enterprises, are not only required to consider the newly emerging markets as the base of clinical trials.”

“We need sufficient resources and rational evaluation capabilities to guarantee the drug evaluation work accomplishment in a  high quality way, and to make rational judgments and decisions within proper time limits.”

“Drug evaluation and approval are an interactional process, and the evaluators and applicants should communicate with each other continuously and convince the other party by using rational data and viewpoints.”

“The capabilities of our staffs are different, which affect the implementation of work. Meanwhile, they do not make an enough systematic studyto professional registration knowledge, which affects the depth of work.”

“We are still worried about the clinical trial area where many problems are involved. Our settlement measures are very prudential.”

“We must balance the interests between national industry and those of overseas-funded enterprises. The opening up of clinical researches will inevitably attract overseas-funded drugs, and therefore, the drug administrative authorities and other relevant administrative authorities must consider and calmly respond to a series of effects arising out of the possession of clinical resources, the occupation of markets, the general public’s availability for drugs from original research, as well as the pricing difference between patented drugs and generic drugs, etc.”

Q: Just now you mentioned globalized drug research and development, saying that the globalization of drug research and development had been inevitable, and it had been a trend for the focus of the drug research and development value chain to move toward China. How should we understand globalization, especially global synchronous development?

Zhang Wei: With the high-speed development of China’s economy, transnational pharmaceutical enterprises have made huge profits from their business in China, and therefore hope to further speed up the listing of new drugs in China, and expect to utilize the advantages of costs, talents and disease resource spectrum, etc. of the countries with emerging markets such as China and India to speed up the efforts of new drug development, so as to enlarge the competition market and reduce the costs for research and development. However, due to the great risks of new drug development, many companies have to be prudential. If we can give play to China’s political advantages and accelerate the establishment and implementation to policy advantages effectively, China will undoubtedly take an early step in respect of bringing in new drug development technologies and funds.

As for globalization, it is also a “double-edged sword” in fact. To the drug administrative authority, “globalization” not only brings opportunities, but also makes us faced with severer challenges. We have the following cognition and viewpoints on global synchronous drug research and development:

Firstly, global drug research and development, as an important part of globalization, have come to Asia, especially to emerging markets.

Secondly, global drug research and development bring challenges to the drug administrative authorities of the emerging markets. We need sufficient resources and rational evaluation capabilities to guarantee the drug evaluation work accomplishment in a high quality way, and to make rational judgments and decisions within proper time limits. Meanwhile, we should keep the consistency of the decisions, and speed up to be conforming with standards and administrative norms step by step.

Thirdly, global drug research and development also bring challenges to the drug administrative authorities in mature markets. As more and more clinical trial data come from emerging markets, the supervisory authorities of mature markets also face the problem which we are facing. That is, how to make use of the clinical data collected from other countries or regions to support the applications for being on listing in the home country. Therefore, we think that the communications and cooperation between the drug administrative authorities of the future newly emerging markets and those of the mature markets will be closer.

Fourthly, global drug research and development also bring challenges to pharmaceutical enterprises. With the continuing enhancement of the technical evaluation capability of drug administration and evaluation institution , pharmaceutical enterprises, especially transnational pharmaceutical enterprises, are required to not only consider the emerging markets as the clinical trial bases, but also pay attention to the cultivation of the technological capability and communication capability of the local drug registration staffs. If the cultivation of such capabilities is ignored, the evaluation time limit might be extended.

Q: As the drug administrative authority of a newly emerging market, especially the administrative authority of China, how to actively respond to the global challenges and continuously make researches for the effective administrative means, so as to better maintain and promote the public health?

Zhang Wei: Here I would like to share with all of you a viewpoint of Dr. Lumpkin, deputy commissioner of U.S. FDA. He does not think that international coordination means replication of drug administration policies or full consistency of practices. So long as be on rational basis, different countries may have its unique practices as the case may be.

To sum up, “more conversation but less confrontation, and more cooperation but less criticism” should become the theme for the drug administrative authorities of the newly emerging markets and those of the mature markets to respond to global drug research and development, strengthen cooperation and realize the win-win situation. As for global synchronous research and development, it is a new subject to the drug administrative authority of China, and “China is ready” should not be a simple slogan but the actions should be taken.

The Evaluations and Approvals Should Be Active, Cooperative and Lawful

Q: In terms of the time limit for evaluation, the pharmaceutical industry pays much attention to the time limit for the evaluation made by the drug administrative authority of China. However, the evaluation quality and efficiency are common challenges faced by the drug administrative authorities all over the world.

Zhang Wei: It’s true. The factors affecting the time limit for evaluation are complicated, but we need to point out a wrong understanding in this regard. Previously, people always thought that the extension of the time limit for evaluation is unilaterally caused by the SFDA. We may see that, according to relevant provisions of the newly amended “Regulations on Administration of Pharmaceutical Registration” which came into force on October 1, 2007, the time needed by the Center for Drug Evaluation for drug technical evaluation is approximately 90 workdays, and the time needed by the SFDA for administrative evaluation is approximately 30 workdays. Therefore, normally, it will take 120 workdays for the clinical trial of a new drug to be approved.

However, few people notice that, the “Regulations” prescribe a supplementary procedure for evaluation. Once the supplementary procedure is started up, the time for the pharmaceutical enterprise to answer the questions raised by the drug administrative authority and to prepare for various documents will not be counted into the aforesaid time limit for evaluation. If a pharmaceutical enterprise ignores the cultivation of the technological capabilities of its staffs in charge of registration, the documents they has prepared are irrational or insufficient, or it is unable to answer the questions of the drug administrative authority timely, the actual time for evaluation will much possibly be extended. Therefore, besides that the drug administrative authority should pay attention to the time limit for its own evaluation, the pharmaceutical enterprise should also inspect their internal procedures to find out to what extent the extension of the time for evaluation is caused by themselves. This is our viewpoint.

As a registration and evaluation institution, we should actively promote the reform of the drug evaluation and approval structure. On one hand, we should accurately define the registration administrative duties, strengthen the macro-policy research, the system operation coordination and the quality progress supervision; on the other, we should, in light of the actual situation on drug declarations, evaluations and approvals, optimize the allocation of drug registration resources, lawfully and reasonably divide the evaluation and approval powers, give full play to the functions of the provincial administrative authorities, and effectively mitigate the work amount of the Center for Drug Evaluation of the SFDA to enable it to concentrate its energy on evaluation of new drugs.

In addition, we should research and formulate the “Quality Management Norms for Drug Registration” (GRP), specify the duties and tasks of each department in the registration link, and regulate their work behavior; we should set up the mechanism for joint consultation between all relevant entities and all departments of drug registration, make it to be normalized, institutionalized and standardized, and strengthen work coordination; we should continuously optimize the administrative procedures for evaluation and approval, and improve the work efficiency; we should also strengthen the supervision, inspection and appraisal to each link and each department of the drug registration, and guarantee the quality of work.

In short, drug evaluation and approval are an interactional process, and the evaluators and applicants should communicate with each other continuously and convince the other party by using rational data and viewpoints. Only if both parties actively cooperate with each other and abide by laws, may the best efficiency be attained.

Q: Although great achievements were made with the State’s administrative work on drug registration in 2009, the problems and insufficiencies were also distinct. What challenges will the future administrative work on drug registration face, especially in respect of encouraging innovations?

Zhang Wei: The drug registration in China mainly faces problems in three aspects.

Firstly, the system, mechanism and bylaws of drug registration are not sound, which restrict the work quality and efficiency. On one hand, the drug registration powers are highly concentrative, the staffs do not match their work arrangement, and the evaluation and approval resources are not strongly adaptive; on the other hand, too many efforts are made on specific affairs while there are not enough time and energy for researching the macro- problems such as policies andsupervision methods innovation, etc., as well as making surveys, which in a certain extent affects the supervision efficiency and quality; furthermore, there is no arrangement or coordination to the whole process, no supervision or inspection to each link and no inquiry into the liabilities at each link, and thus the sense of responsibility is not strong at some links, and the supervisory work is in a superficial form, which also affects the supervision efficiency and quality in a certain extent.

Secondly, the legal construction lags behind, which affects the supervisory function. The uncoordinated research and supervision affect the exertion of the composite of supervisory force; the relevant ancillary documents have not yet been fully promulgated and the encouragement innovative measures are not specific, and such fact affects the implementation of the “Regulations on Administration of Pharmaceutical Registration”.

Thirdly, the capabilities of the staffs are different, which affect the implementation of work. The capabilities of our check personnel need to be further enhanced, and the personnel for checks are not allocated reasonably. Especially, we are short of personnel for checks in the areas of pharmacology, toxicology and clinic, and the quality of check work is therefore affected; while they do not make an enough systematic study to professional registration knowledge, which affects the depth of our work.

To sum up, the problems mentioned above affect the implementation of the newly amended “Regulations on Administration of Pharmaceutical Registration”, the quality and efficiency of the drug registration administration in China, and the drug safety of the general public. Such problems urgently require the food and drug administrative authorities at each level to pay high attention, make serious researches, and take powerful measures to settle them as soon as possible. After the rectification, governance and regulation to the research and development institutions, the manufacturers and their registered products in recent years, the present order of the research and development area in China has been greatly improved. However, we are still worried about the clinical trial area in which many problems are involved, and our settlement is very prudential.

The favorable factors propelling drug clinical trials are that China’s drug research and development level can be enhanced, more research and development funds have been gained, and corresponding administrative regulations and bylaws may also be promoted and improved. However, in view of the macro-administration of the State, we must balance the interests between national industry and those of overseas-funded enterprises. The opening up of clinical researches will inevitably attract a good many overseas-funded drugs, and therefore, the drug administrative authorities and other relevant administrative authorities must consider and calmly respond to a series of effects arising out of the possession of clinical resources, the occupation of markets, the general public’s availability for drugs from original research, as well as the pricing difference between patented drugs and generic drugs, etc.