The essence of the drug listing permit holder system（一）

Copyfrom： Release time：2019-05-21 The editor：

 The drug listing permit holder system is the current general management system in the field of drug safety in the international community. It is the basic legal system that runs through the entire life cycle of drugs, and is the subject management system with the core content of obligations and responsibilities. It has been nearly four years since the trial of the drug listing permit holder system in China, and some innovative achievements have been made. It is necessary to systematically summarize and deeply ponder this innovative practice.
 
The essence of the MAH system
    
       What is the essence of the drug listing permit holder system? This requires careful research. This determines the basic positioning of the operation of the system, affecting the series of institutional arrangements such as the conditions, rights, obligations and responsibility of the listed license holders.
Regarding the essence of the system, some people think that the registration applicants are let go, some people think that the commissioned production is released, some people think that the registration certificate is released, and some people think that the group holds it open. In fact, these are the dividends of the system, but they are not the essence of the system.
The ancient Greeks once said: The emergence of a new concept is not a simple adjustment of the connotation and extension of things; the emergence of a new concept often marks the arrival of a new era. Is the “drug market permit holder system” a new concept? Some people argue that the system of drug listing license holders is not a new thing in China. This view is debatable. The creation of any new system has its own process of gestating, growing and maturing. In the past, China had a registration system but this was not a true listing permit holder system. Because under the registration system, the registrant's responsibility for the management of the drug's entire life cycle is implicit, clear or dark, and does not form a complete system of responsibility. The separation of drug development licenses and production licenses marks the emergence of the drug listing permit holder system. Under this system, drug developers have entered the stage of drug management in an independent manner, bringing a series of deep-level changes to the drug management system.

      The core and essentials of the system of listing license holders shall be the management responsibility of the holder of the listing license to bear the quality and risk of the drug throughout its life cycle. Here, there are three aspects that need to be highlighted:
      The first is "listing." The English version of the “Listing License Holder” is “Marketing Authorization Holder”. Some people ask, what is the listing of drugs in China? What is a drug marketing license? Is the consignment of China's drug marketing license consistent with the drug listing permission in Western countries? At present, there are two licenses in the process of listing drugs in China, namely product registration and production license. Without any license, drugs cannot enter the production, circulation and use fields. Therefore, some people say that the production license is the real marketing license. Careful analysis, this conclusion has an important mindset defect, that is, the first product registration, and then the production license. In fact, in foreign countries, there is often only product registration, and no production license. In China, it is not necessarily "first product registration, after production license." In the institutional reform of the State Council in 2013, taking into account the duplication of China's pharmaceutical production and operation licenses and drug quality management system certification, it is decided that the two will gradually become one. That is to say, there were two options for retaining the drug production license or GMP certification. If the GMP certification is retained and the production license is cancelled, and the GMP certification is further deepened into GMP inspection, isn't the product registration a marketing license? If the registration certificate can be transferred to the market, isn't the product registration at this time the listing license? Therefore, the meaning of the drug marketing license should be examined and grasped with an international perspective and development perspective.

      The second is "management." The holder of the listing license shall bear the “management” responsibility for the whole life cycle of the drug according to law. It has been argued that holders of marketing licenses bear civil liability for the entire life cycle of drugs. This conclusion is undoubtedly correct, but this conclusion is not the core of the system. The relevant civil liability, the Tort Liability Law, the Consumer Rights Protection Law, the Drug Administration Law and other laws have been stipulated. It is only necessary to further clarify the legal status of the listed license holder as the “producer” of the drug. The essence of the system of listing license holders is essentially defined from the perspective of enterprise management, that is, the license holders are responsible for the quality and risk management of the drug throughout its life cycle.
       The third is "legal." The management responsibility of the listed license holder for quality and risk throughout the life cycle of the drug is a general statement. Specifically, whether the license holder of the listing is responsible for the quality and risk management of the drug development, production, distribution, distribution, retail, use and other activities depends on legal provisions and contractual agreements. The modern socialized production process is extremely complicated, and the trading activities and transaction forms between the trading entities are extremely complicated, and it is impossible to stipulate all matters as legal matters. Some matters can be stipulated by law, and some matters can be agreed by contract. The holder of the listing license assumes management responsibility for drug development, production, distribution, distribution, retail, use, etc. The management here includes both quality management and risk management, such as suspending clinical trials, suspending production and sales of products, recalling products, and modifying Instructions, etc.
       The management responsibility of the listed license holder is divided into two aspects: First, the responsibility directly related to the transfer of ownership of the drug. In this case, the management responsibility of the listed license holder is transferred as the ownership of the drug is transferred. In the stage of drug development, production and distribution, the holder of the listing license assumes the management responsibility for the quality risk of the drug because it generally holds the ownership of the drug. This is the key to the system of listing license holders. In the wholesale, retail, and use links, the ownership of the drug generally shifts. Under such circumstances, part of the responsibility for the quality and risk of the drug is borne by the wholesaler, retailer, and user. The second is the responsibility unrelated to the transfer of ownership of the drug. The holder of the listing license is the “producer” of the drug, and has the deepest and most comprehensive understanding of the quality risks of its products. It also bears certain reports on the adverse reaction reports, problem product recalls, etc. of the distribution, retail, use and other links. legal liability. This responsibility is determined by the special status of the holder of the listing.
    
The advantages of the MAH system    
       With the increasingly fierce competition in the internationalization of the pharmaceutical industry and the growing demand for safe, effective, quality and accessible drugs for the people, the drawbacks of the “bundling” management model for drug registration and production licenses in China are increasingly apparent, and it is necessary to adapt to the market economy. Development and innovation drive strategies need to fully implement the drug listing permit holder system. Practice has proved that the drug listing permit holder system has the following significant advantages and deserves to be fully promoted and accelerated.
First, encourage drug innovation and enhance competitiveness. The implementation of the listing permit holder system allows the drug research and development institution to submit the drug clinical trial application and drug listing application as the drug registration applicant, and obtain the drug approval document number to become the marketing license holder. This means that drug research and development institutions can enjoy the ultimate market benefits of technological innovation as the identity of the license holder, which will stimulate more R&D institutions and researchers to engage in new drug creation.
The second is to optimize resource allocation and promote industrial concentration. The system of listing license holders has many institutional dividends such as the application for registration, the release of the commissioned production, the release of the license, and the release of the group. With the full implementation of this system, the vitality of market competition and survival of the fittest will be further developed. The pace of innovation and industrial concentration will be further accelerated, and the quality development of quality change and efficiency change will be further consolidated.
      The third is to implement the main responsibility and strengthen the whole process management. For a long time, the quality risk of drug development in research, production, circulation, use and import has been controlled by different entities, and the closed-loop management system with complete system and interlocking has not yet been fully formed. After the implementation of the listing permit holder system, the listed license holder as the “producer” of the drug is the first responsible person for the safety, effectiveness and quality of the drug, and the preclinical research, clinical trial, manufacturing, distribution and distribution of the drug. , adverse reaction monitoring, drug alert and other management responsibilities, which is beneficial to the listing permit holders to comprehensively strengthen their quality management system construction, and extend the review of the partner's quality management system, thereby strengthening the drug life cycle quality system, effective control Drug quality and safety risks.
      The fourth is to promote management innovation and achieve management upgrades. Whether it is for the regulatory authorities or for pharmaceutical companies, the implementation of the listing permit holder system involves innovations in management concepts, systems, mechanisms, methods, and strategies. From the perspective of enterprises, listed license holders need to establish a new drug quality assurance system to ensure the full implementation of drug quality risk responsibilities. From the government's point of view, innovative methods of drug regulation are needed to further improve the quality of supervision and regulatory effectiveness.