Drug marketing authorisation holder system panorama,China Mingxuan

Medical network on April 19 - in November 2015, the 12th session of the standing committee of the National People's Congress through the 17th meeting of the standing committee of the National People's Congress on authorization in some parts of the state council to carry out the drug marketing authorisation holder system pilot and the decision of the relevant issues ", marks the Chinese drug marketing authorisation holder system (hereinafter referred to as the "holder system) to start. Holder system is adopted widely in the international community drug management system. , which is the core of the drug management system reform, the holder of the system of drug management system innovation of our country fundamental, overall and strategic impact.

Seen from the relationship of drug registration applicant and production enterprise, at present, there are two main types of international system: one is the separation system. Drug registration applicant and manufacturing enterprise can be a different subject, after registered applicants obtain authorisation, become the drug marketing authorisation holder, holder can be engaged in drug production, sales, also can entrust other companies to pharmaceutical production and sales, holder is responsible for the whole life cycle of drug quality. The second is bound. Drug registration applicant must be a pharmaceutical production enterprise. If the applicant is a research and development unit, it must be with production enterprises as a joint declaration, the common or individual separate declaration by production enterprises, research and development unit became of the drug marketing authorisation holder. Pharmaceutical administration law of the identified system in China is the "bundled" system. Under this kind of system arrangement, research and development unit as the applicant with the document of approval for production enterprises jointly owned or the approval document number of research units, hold phenomenon, there is a property right is fuzzy, the responsibility is not clear.

From the drugs listed license involved in each link of subject relations, the international community is also divided into two systems: one is TongYiZhi, namely drug quality by a responsibility unified closed-loop control in whole life cycle, this system is the holder of the system. 2 it is dispersed system, i.e. by multiple main body of drug development, production, sales and other activities for sectional management. Each main body responsible for related link of risk prevention and control. The pharmaceutical administration law system is a distributed system.

Holder system in the research, people are used to understand holder system as medicine in licensing system, therefore the main focus on pharmaceutical marketing authorisation section, this understanding is not comprehensive. Holder system covering the whole process of drug listed before and after the public management, in the drug management system is the basic system of legal status. Research holder system, need to grasp the basic position of this system, namely the system of the core word is public license, or the holder?

Generally speaking, public license system as a link management system, and belongs to the category of "procedural law", it involves application subject, application conditions, application procedures, the application documents, review, review of standards, review procedures, time limit of the review, the review conclusion, licensing authority, licensing procedures, licenses, license file, license validity, etc., it is mainly around the application, review, examination and approval of the basic program to expand. And the holder of the system, as an element management system, belong to the category of "body", involving the status, qualification, conditions, relationships, rights, obligations, responsibilities, etc. Holder system is at the heart of the word "holders". Only "holders" system, can cover drug quality of whole life cycle. It just like drug inspection, appraisal system, inspection institutions, issued by the appraisal institution is conclusion, expert opinion, therefore, people tend to test system, appraisal system to a system of "documentary evidence" category. In fact, the inspection conclusion, expert opinion is personnel, appraisal personnel's understanding and judgement. From the point of management elements, inspection system, appraisal system is the main specification of agency qualification, personnel qualification, ability quality, professional ethics and practice discipline, etc. Therefore, in essence, inspection system, appraisal system belongs to the category of "witness" system.

About what is meant by "public license", the Chinese and foreign practices have different understanding. The holder of the system from the west. As western countries more product license management without business license management, so the product license is essentially for authorisation. In our country is a product license and business license of dual licensing system, which is different from western developed country, therefore, it is thought that defines product registration as authorisation in our country, it is not enough accurate. In fact, after shall practise a system of holder, the holder of the entrust other enterprise production and operation, this itself is a kind of market activity, therefore, called product registration authorisation in our country, will not produce semantic confusion and cognitive impairment.

About why called "holder", not "everyone"? Under the holder of the system, the holder holding a given by the administrative organ "rights" or "qualification", the "right" or "qualified" has the property of a certain property rights and personal rights, but also different from pure property or personal rights. The concept of "all" is commonly tangible property rights system is to use the concept of property rights system, its power including possession, use, dispose and benefits. Intangible property rights such as the intellectual property field generally don't use the concept of "all". The power of intangible property rights, there is no unified, standard, authority, is believed to hold, use, dispose and benefit, the punishment of more diverse forms, such as transfer, transfer, etc. In fact, the word "hold", which can more accurately reflect the public license can transfer the property rights of attributes.

Any legal system design has its profound social and cultural background, the holder of the system is the result of market economy system. Under the market economic system, any civil subject can be equally engaged in drug research activities, and each civil subject can be a marketing authorisation holder, does not depend on their identity, status, but depends on whether they have the corresponding ability. With the progress of science and technology, in all key elements of productivity, enhance the value of science and technology, the holder of the system design to further reveal the value of the science and technology. Holder at the same time, the implementation of system, means that the commanding heights of the drug quality management from the transfer of production to develop links, further reveal the quality of the products is the result of design concept, the drug quality management has entered a new stage. So, the holder of the system is the drug management system under the condition of market economy.

Pharmaceutical administration law in our country to establish the authorisation from drugs production enterprise held by the system, originated from the planned economy era. At that time, due to the limitation of productivity level, drug research and development innovation ability is insufficient, enterprise production of drugs mainly generic drugs, drug management key link in production. In this special historical period, the body of the drug development basic is state-owned enterprises, the subjects of drug research and production of this kind of unity, is fit in with the economic and social conditions. Under the condition of market economy today, this system has been seriously limits the drugs industry division of labor and cooperation, waste a great deal of social resources, hampering the enterprise growth and progress. In addition, the drugs listed license with the production license of an enterprise's bundle model, to a certain extent, is also a natural economy concept and a product of the traditional management thinking.

One is to encourage drug innovation, enhance competition ability. After many years of accumulation, drug research and development innovation ability of our country has made significant progress, but there is a certain gap between the developed countries. According to related statistics, in 2015 nearly $600 billion in global innovation medicine market, and our market innovation medicine less than $10 billion. In October 2016, the China medical association of business management and so on four big industry organization jointly issued the "build the sustainable development of Chinese medicine innovation ecosystem in the report pointed out:" around the world, with vitality and competitiveness of pharmaceutical innovation industry must be from the health, virtuous cycle of innovation ecosystem ". System innovation is the core element of ecosystem. Shall practise a system of holder, to encourage research and development institutions and scientific research personnel engaged in drug innovation, and acquire the license of the drugs listed will change the original system of scientific research personnel only through technology transfer or silent stake for short-term interests or the interests of the silent embarrassment, activate market effectively. At the same time, practice the holder system, research and development unit or researchers can entrust production to drug rapid industrialization, the formation of the stable investment relationship and a better investment return expectations, this will greatly arouse r&d institutions and scientific research personnel in the enthusiasm of drug research and development innovation, speed up promote innovation and international competitiveness of China's pharmaceutical industry.

Second, optimize the allocation of resources, promote industrial concentration. 4246 at present, our country has all kinds of pharmaceutical production enterprises, the production scale of 50 million yuan of the following accounts for more than 60%. Approved drugs in China is about 15000, drug approval number about 168000. Overall, China's pharmaceutical enterprises still exist "more, small, scattered, low" phenomena, overcapacity serious, the homogeneity competition is intense, huge resource waste. This phenomenon is related to Chinese medicine industry development stage, also associated with the value orientation of legal system of our country on drug administration. Holder system, after the enforcement of drug research and development institutions and the researchers were able to build a drug production enterprise, also can entrust drug production enterprises, so that you can avoid enterprise "instead of", "conveniently small" low level repeated phenomenon. At the same time, the developer can make drug fast industrialization, quickly occupy the market, improve the effective utilization of resources. Can be expected, the holder of the system, the full implementation of the pharmaceutical industry in China will quickly into the differentiation and reorganization of the period, the pharmaceutical industry concentration, innovative cluster will further accelerate the pace of market competition, a vigor of the ecological optimization will further.

Three is to carry out the corporate responsibility, strengthening the management of the whole. Risk is the core of the management, responsibility is the core of management. Drug administration law system is the drug of the rights, obligations and responsibilities of stakeholders system arrangement, the core content can be summarized as full implementation of comprehensive prevention and control of risks and responsibilities. Under the different legal system, the corporate responsibility to carry out the breadth, depth and strength are different. Under the holder of the system, the holder is responsible for the whole life cycle of drug quality, this kind of clear and strict responsibility system will effectively strengthen the holder "from the lab to the hospital" full implementation of the management responsibility. Holders will focus on is not only the pharmaceutical research and development, will also focus on pharmaceutical production, warehousing, transportation, sales, and many other links, because the drug is in the interests of the enterprise system, the quality of life of the.

Four is to promote management innovation, realize management to upgrade. From the perspective of management, agricultural era, industrial era and the information age, the concept of management, resources, elements, focus and not be exactly the same way. Agricultural era for the natural economic society, pursues is the property of the static view of all; Industrial age to the market economy society, pursues is the property of the dynamic use of view; Economic and social information age for sharing, pursues is the wealth of open sharing. Experts and scholars have argued that the pharmaceutical administration law in our country based on the planned economy era, more or less, or Ming or tacitly with planned economy system, the natural economy and society and some traces of the traditional management thinking. Drug administration shall practise a system of holder, the direct object of transfers from multiple subject to a single subject, the core content of management transfers from the entry qualification management to management system capacity, the basic way of management will shift from traditional management to modern management, drug management will enter a new era of intelligent management. After implementation, in addition, the holder of the system will be a series of profound changes in drug management way, such as the administrative licensing will further simplify, will further improve the regulation efficiency, will further enhance service level, in line with the current and better to delegate the pipes in combination with the basic requirement of optimization services.

From the perspective of historical development, any system design is not perfect, each system has its advantages and disadvantages, gain and loss, the legal system design of art is to promote the beneficial and abolish the harmful, akira gain or loss. Holder has been introduced in front of the system of comparative advantage, also describes the holders of the qualifications, then, from the perspective of system design, the holder of the system is there some endogenous? Need to strengthen management from the aspects of what?

Look from the current study, under the holder of the system, the holder of the risk management capability is likely to increase, namely holder in entrust other enterprise production or sell drugs, ability of the trustee for effective supervision. Experience from abroad, the holder can supervise the trustee may also entrust a specialized agency to supervise the trustee. Regulators should to holders of the supervisory ability of continuous investigation, when necessary, timely to the risk of prompt or responsibility for questioning.

Can be seen from the grassroots, to find someone to holders of the eligibility of the trustee. At present, the holder of the system of the pilot is still ongoing, pharmaceutical production enterprise separation of professional division of labor is still in exploration. Can be expected, with the drug management system reform deepening, especially holder system steady progress, part of the pharmaceutical production enterprise may transform the trustee drugs production enterprise, the holder of the choice to the children of the trustee, may also need to market a running-in, but that in itself belongs to the market transaction behavior, rather than the risk faced by the holder system design.

Can be seen from the grassroots, some researchers to holder can timely report adverse drug reactions concerned. Monitor and report adverse drug reaction is holder of legal obligation, is the whole life cycle of drug quality risk management requirements. At present, the part of the pharmaceutical enterprise risk consciousness and responsibility consciousness, not strictly fulfill its obligation to adverse drug reaction monitoring report is relatively common. Should be admitted that, when the owner entrust other production, if you don't build good benefit constraint mechanism, adverse drug reaction monitoring report duty could face a more difficult situation, deliberately withheld adverse drug reaction should be established for this incident report and result in punitive damage compensation mechanism, and at the same time, regulators should further strengthen supervision law enforcement and the adverse drug reaction monitoring report as the focus of the holder to check. But strictly speaking, this difficulty is not peculiar to the holder system itself, is a drug management system overall design and operation mechanism perfect.

In addition, at present, the pilot period, the holder of the entrust other enterprise production, there are regional restrictions. After fully implementing holder system, entrust production should not be limited to the region. At this point, the enterprise production and business operation activities of a trustee is home to the holder is responsible for the supervision department, or by the supervision department is responsible for the enterprise is located as a trustee for further study. In the future, pharmaceutical production the trustee may be a common phenomenon, therefore, it is necessary for regulation on the supervision and administration of pharmaceutical production by revised perfect, strengthen the holder of the local regulatory authority and the regulation of the entrusted enterprise local regulatory authority division of labor and cooperation, jointly do holder under the system of drug production and business operation activities of the regulation.

In pilot study holder system, "people" to what can be the applicant and holder, pay special attention to all parties concerned. The main reason is: one is about the dividend holder system reform how much? It is all kinds of civil subject, or part of the civil subject, can become the authorisation of the applicant and holder? Second, what is the value orientation of marketing authorisation holder system? Innovation is to encourage drug, or optimize the allocation of resources? To carry out the corporate responsibility, or promoting management innovation? Here, the value choice of freedom and security, efficiency and justice is what? It also become the key of the system design.

From the perspective of the legislative technology may be described in three ways: one is the enumerated type. Such as "the standing committee of the National People's Congress on authorization in some parts of the state council to carry out the drug marketing authorisation holder system pilot and the decision of the issues related to" make clear a regulation, to allow drug research and development institutions and researchers obtained drug approval number, take the corresponding responsibility for drug quality. Issued by the state council general office on drug marketing authorisation holder system pilot notice for drug research and development institutions or scientific research personnel, pharmaceutical production enterprises. The advantage of this way is that they can better reflect the policy guidance of system innovation, insufficient is not reflect the equal status of all kinds of market subjects. 2 it is described. The direct description of legislation can be the basic condition of the applicant and holder, such as innovation ability, management ability, responsibility, etc. Issued by the state council general office on drug marketing authorisation holder system pilot notice specifies the basic conditions of the applicant and holder. Three is a hybrid. To list and describe. The state council general office on pilot notice issued by the drug marketing authorisation holder system is actually adopted the hybrid.

In the study of the applicant, the holders of the qualifications or conditions, need to be considered an important premise, namely due to reasons such as inheritance, merger and acquisition and transfer, the applicant and holder in the application process and product market permission after can make changes, this is the need of drug free flow of production factors. At present, the pilot program allows only scientific research units, research and development personnel, production enterprises become the holder, the system more location in encouraging drug innovation. Holder system in the research, related to the applicant, the holders of the conditions, should consider the following three aspects:

One is the development ability. This is to become the first condition of the applicant, the holder. Skills developed, that is, technical ability, innovation ability. The applicant will eventually become a holder, depending on whether the application of drug safety, efficacy and quality controllable. Whether new drugs or generic drugs, traditional Chinese medicine and western medicine, the applicant, the holder of the general conditions should be the same, the applicant, the holder shall have certain research and development capabilities. Also the scholar thinks, because the applicant can apply for registration by techniques of purchase, the applicant and holder can also do not have ability to develop. In essence, the obligations from the holder, even if their purchase technology, should also be directly or indirectly with research and development capabilities. Technology regardless of the personal data of the original owner is who, the applicant or the holder of the technology should be to master all personal data, bondholders won't be able to guarantee the effectiveness of the performance of the whole life cycle of drug safety responsibility.

The second is management skills. Due to the applicant and holder of separability, and transferability of pharmaceutical production technology, management ability of the applicant and holder is different. Management capabilities include many contents, such as drug clinical trial management ability, sample trial production management ability, ability of drug production and business operation management, etc. As the applicant and holder, it shall meet the drug clinical trial management and pilot production management ability. As holders, if their own production or entrust others production, it shall also have the production and business operation management ability. Here it is important to note that the management of different capacity, regulators are listed in the permission request for inspection, review, or listed in the application process and after the product registration request for inspection, review, respectively, need to be carefully studied. In a word, drug registration link should implement the principle of simplicity, seize the essence and the key, avoid cumbersome requirements and excessive regulation.

Three is responsibility. Strictly speaking, the responsibility ability including management and compensation ability. Here mainly deals with the compensation ability. Here need to answer questions on five aspects: one is what is a compensation ability? So-called compensation ability, generally refers to the drugs development, production, management activity causes any damage to other people, the applicant, the holder of the ability of economic compensation. 2 it is who has compensation ability? Which subject have compensation capability in research, the majority of people in addition to the compensation capacity of legal person units, no doubt to unincorporated organization and the compensation of natural ability common concerns. Starting from the concept of "ownership" by accident, the compensation is not legal person unit capacity must be compensation ability than entity without legal personality. 3 it is compensation ability comes from where? Must be based on its own property as a compensation, or can be purchased for compensation from the insurance or other guarantee way? In the contemporary society, the answer to this question is clear, for sure. Fourth, when to have compensation ability. Is the need when drug registration applicant and holder have compensation ability, with compensation ability was a pharmaceutical production need? In the "time lag", the applicant, the holder of the compensation capacity will change? Fifth, in the administrative management system in the design of the civil matters specified in items (whether need? Whether the government management of the holder for civil compensation obligations must be responsible. What is the legal value orientation of the system design? These problems are involved in regulation of some deep-seated problems.

In fact, from research and development ability, management ability to responsibility, this is for the applicant, the holder of the qualifications of progressive management requirements. Here, need from the whole lifecycle management of drug quality in time and space arrangement, and should not be limited to the drug marketing authorisation. In drug registration link, should be emphasized the applicant, the holder of the research and development ability and management ability, without having to consider more compensation ability, such as well as for the applicant melancholy, can also be used for regulatory burden, to set up to encourage drug innovation of good ecological environment.

The content of the legal relationship is the rights and obligations relations. As an independent civil subject, pharmaceutical marketing authorisation holder shall enjoy the legal regulations of pharmaceutical enterprises in all kinds of basic rights, but also to undertake the basic obligation of the pharmaceutical enterprises established by law. How to clear holder in legislation and entrusted enterprise rights, obligations and responsibilities of the division, is more complex and more difficult problem. Which should be explicitly stipulated by legislation, which can be set forth by the entrust agreement between the parties, worthy of serious study. Any rights and obligations relations are not abstract, the relation between rights and obligations, it should be placed in the specific legal system and legal practice. Study drug marketing authorisation holder of rights and obligations, can be viewed from two aspects: one is the holder of the production and sales of their drugs, the rights and obligations of the holder has fully enjoy the rights of all market main body, but also undertake corresponding obligations; The second is the holder of the entrust other enterprise production, sales, drugs when the rights and obligations. At this point, the holder and the rights and duties in the relationship between enterprises as a trustee shall be bound by law and contract. Below, is only holder system design on a few rights and obligations are analyzed.

One is the transfer of the rights. Whether holder may transfer documents for authorisation, this is a topic of debate for a long time. About the legal attribute of authorisation document, has made a brief description. Theoretically, authorisation document is contains the rights of the dual attribute of property rights and personal rights, and to this is the key of the problem. Starting from the property right attribute, marketing authorization documents can be transferred. Starting from the person or the administrative attribute, the transfer of authorisation document you will need to perform a certain program. Our country "administrative licensing law" article 9 of the regulations, "according to the law of administrative licensing, in addition to the laws and regulations in accordance with the statutory conditions and procedures may be transferred, shall not be transferred". Authorisation document of the transfer shall be stipulated by laws and regulations to make clear. At present, there are no rules in the existing laws and regulations for authorisation documents can be transferred, the supreme people's court, the relevant judicial interpretation also banned drugs authorisation document transfer. The current practice by way of transfer of technology transfer authorisation document "flexibility". Can give authorisation document transfer, therefore, is beneficial to drug innovation vigor, promote social division of labor, professional by conducive to achieve optimal allocation of resources.

The second is entrusted by the right. Holder of the biggest highlights of the system is a marketing authorisation holder can no longer bundled with pharmaceutical production enterprises. The business activities of the derived and extension, the holder of the three paths can choose: your factory production and sales, entrust other enterprise production and sales, transfer marketing authorization documents. Entrust other enterprise production and marketing of drugs, holder can without any increase in plant facilities and personnel, under the condition of capacity expansion and occupy the market quickly, to curb low level repeated construction has the very vital significance. Holder and the relationship between the production and operation enterprises, belong to the commissioned relations. This delegation relationship, which content into the legal adjustment, which is prescribed by agreement, need careful study.

Three is to monitor the rights and obligations. Holder entrust enterprise production and marketing of drugs, holders have to supervise the production and marketing activities of enterprises entrusted rights. At the same time, the supervision is also the principal the holder of a basic obligation. This is in the entrusted the basic principles of legal relationship. Supervision, including what content, needs further study. Production and business operation activities of the entrusted enterprise whether accord with the requirement of drug production and business operation, whether meet the requirements of the production and business operation and the quality control standard and whether meet the requirements of the entrusted agreement should be incorporated into the scope of supervision.

Four is release of rights and obligations. Owner entrust other enterprise production, the one with the final decision of drug release is a holder research system more heated debate. In fact, the final release right is inherent rights holders. Since the holder is the owner of a pharmaceutical marketing authorisation is apparent producers of the drug, so, the holder of the naturally have to drug quality inspection and the right of release of drug sales. Eu demands that the quality of the marketing authorisation holder is empowered to final product release (QP), and no clear requirements on the U.S. allow actual production enterprise instead of the holder. Holder can be the final release right delegated to the manufacturer or a third party, but this does not exempt from holder shall have the legal responsibility.

Five is the duty of monitoring and evaluation and report. Post-marketing adverse drug reaction monitoring and evaluation and report, it is the duty of the holder of the obligations or actual production enterprises, in the study of holder system is a controversial topic. Monitoring and evaluation is the main content of the whole life cycle of drug management, is an important part of drug post-marketing management. Post-marketing adverse drug reaction monitoring and evaluation, it is the responsibility of the holder inherent. Theoretically, the holder can also entrust adverse reaction monitoring and evaluation and report production enterprise or a third party, but this does not exempt from holder shall have the legal responsibility.

One is the civil liability. Drug marketing authorisation holder production and sales of the drug quality problems, thereby causing loss to the consumers, the holder shall bear the corresponding legal responsibility. If the quality problem is caused by the actual producers or sellers, on behalf of the holder in the compensation after can recover from the actual producers or sellers. Also, the consumer to make a claim for the actual producers or sellers, if not the responsibility of the producers or sellers actually, actual producers or sellers after the bear first responsible, can recover from the holder.

Second, the administrative responsibility. Entrusted enterprise has the violation behavior, in the process of production and business operation in the administrative liability shall be investigated for entrusted enterprise at the same time, whether to need to pursue the responsibility of the holder? This depends on whether holders of fulfilling the duty of the kindhearted administrator. If the marketing authorisation holder to the entrusted enterprise violation behavior does not exist the behavior of the intentional misconduct or gross negligence, the marketing authorisation holder not bear legal responsibility. What is a good manager's responsibility? At present, China's relevant laws and regulations did not make clear a regulation. Common law countries there are a lot of case law, review method and demonstration method to establish some related rules, is worth using for reference. In our country, in addition to the relevant laws and regulations, guiding case also can set some rules gradually. If the marketing authorisation holder together with the entrusted enterprise implement violation behavior, it shall be jointly liable.

One is whether the field of traditional Chinese medicine (TCM) can implement holder system. The holder of the system from the west. Some scholars think holder system is not suitable for Chinese traditional medicine. The reason is that many Chinese traditional medicine is difficult to obtain patent protection or trade secret protection, especially the ancient classic square, is already known public technology. In fact, the technology of state ownership, not influence the key holder system. Generally speaking, determines whether a drug area will use holder system, mainly depends on three elements: one is whether you need pharmaceutical production licensing the product; The second is whether pharmaceutical marketing authorisation can transfer; Three is whether the drug can entrust production. According to the factor analysis, the traditional Chinese medicine production need to acquire the license of the listed Chinese medicine also can entrust production or license transfer. The TCM holder system could be implemented. As for the part of Chinese traditional medicine, such as the transfer of ancient classic square if there is a market demand, the holder system need to focus on is not the issue. In ancient Chinese medicine classic square also involves other complex problems, such as ancient based on whether the individual is suitable for the problems listed as drug, traditional knowledge protection, should be specially considered when drug marketing authorisation. Special case should not be the basis of legislation. This is the perfect drug management system need to focus on problems.

Second, special management medicine whether can implement holder system. Narcotic drugs and psychotropic drugs and other special management of drugs is strictly controlled drugs, the strict control about drugs development, production and supply, involving both fixed-point production and fixed-point business license, also involves the circulation channel control. Therefore, special medicines should not be shall practise a system of holder. Some experts argue that drug implement special management, transfer, delegate opening policy, easy to cause drug abuses events occur.

Holder system is adopted widely in today's international society drug management system, is the drug management system under market economy system, is the basic system in drug administration law system, is the important system represent the future direction of pharmaceutical administration. System at present, the holder of the pilot also is limited by region and variety, the system of the dividend has not been maximum release. Should be bold and draw lessons from international successful experience, to speed up the pharmaceutical administration law revision of the relevant system, advancing a holder of the implementation of the system.