The core content of the MAH system is the separation of the drug approval number and the production license, allowing pilot drug research and development institutions and researchers to obtain the approval number of the drug, and to assume responsibility for the quality of the drug.Before the introduction of the MAH, our country is the implementation of the marketing authorization and the production license of the unified bundled management model, only the manufacturer can apply for the drug registration, and obtain the final approval number of the drug. The company's license is a single bundle of marketing and manufacturing licenses, and only the manufacturer can apply for drug registration and obtain the final drug approval number. Background Domestic Background Before the introduction of the MAH system, China had a similar system: a commissioned production system and a technology transfer system. It is worth noting that the commissioned production system is not a product of production licensing and marketing authorization under the only access system, according to the current commissioned production of the provisions, can only be entrusted to the production of the enterprise has this approval number of the enterprise to outsource, but also the commissioning party and entrusted to the party are manufacturers, and its own approval number is not entrusted with the change. It can be said that the commissioned production itself is only in the possession of the enterprise has a technical transformation and other production conditions do not have a temporary arrangement. The technology transfer system is based on drug manufacturers, drug technology transfer is applicable to three kinds of situations: 1, part of the new drugs, preparations and raw materials for transfer; 2, imported registration to domestic; 3, including some mergers and reorganization and *** with the transfer of the control system, as well as the overall relocation or merger after relocation, and even to give up all of their own dosage forms. International Background MAH in the international community in fact has long been passed, the mainstream developed countries and regions generally adopted the system of marketing authorization holders of medicines. The EU has adopted a separate system of listing management, with two separate MAH and PLH as the application, and the MAH can also produce on its own, or entrust the product to different producers to produce. The manufacturer is only a part of the declaration, and after receiving the declaration, the competent authority separately conducts on-site verification and GMP review and certification of different situations for the manufacturer. The United States is similar to the European Union in that any qualified entity can file with the FDA, and the separate regulations for manufacturers do not restrict MAHs from also serving as drug manufacturers. During the marketing authorization process, the FDA also separately reviews manufacturers and determines the requirements for sampling of product facilities and so on. After 2005, Japan also adopted a separate marketing and production of the marketing authorization system, but it is characterized by its own innovative creation of the marketing licensee system, that is to say, he has a MAH access prerequisites, only to get the first to obtain the administrative license qualification, and then can be carried out on the market of the drug application. At the same time, it also has some special provisions, first of all, MAH must have some of the main management responsibilities of the job set up, including sales management subjective, quality assurance subjective, marketing safety control subjective, three have certain qualifications of the full-time management of the function of staff. MAH system advantages First, the mobilization of drug research and development institutions and researchers research enthusiasm MAH system introduced, scientists research and development of pharmaceutical property rights will be used to attribute to the holder, which will attract more researchers into the new drug research and development team, to improve the strength of China's pharmaceutical research and development, and to change the past generic drugs, "imitation, but not strong," the embarrassing situation. Second, it is conducive to the adjustment of industrial structure and resource allocation, to promote the professional division of labor, improve industrial concentration, to avoid duplication of investment and construction At present, China's domestic drug manufacturers are many, small, scattered, which has a lot to do with the drug approval system. Due to the reluctance to transfer their own varieties to other manufacturers, and at the same time hope that their own varieties can be listed, many pharmaceutical companies often choose to build a plant for a variety of varieties. MAH system was introduced, pharmaceutical companies can be entrusted with the production conditions of the enterprise to produce, so as to focus on their respective specialties in the professional division of labor. Third, conducive to the implementation of the main responsibility of enterprises In some drug incidents, drug manufacturers, operating companies, medical institutions and even R & D institutions are very difficult to define the responsibility, which appeared to be involved in each other, each other's restrictions, the victims are delayed to get a fair solution. MAH system was introduced, the holder of the marketing authorization of the drug is the product of the responsibility of the main body, the product of any problem, all the The chain link is responsible for it. Fourth, it is conducive to avoiding risks in the research and development process There are many risks in drug development, and even many new drugs have been on the phase III clinical, only to be proved that there is no definitive efficacy, which is very heavy for drug companies and investors. Because, under the current registration management approach, the initial investment needs:Before reporting production, the entire R & D in the application for production to have the appropriate conditions for the production of drugs, the entire workshop, equipment should be installed in place, at the same time, but also need to invest in hardware, including software, personnel, equipment, and so on the match. Once in the varieties listed before the emergence of any wind, the investment will have to hit the water, these equipment will not be put into production in a timely manner because of the turn of the wheel, wait until the next round of drug review, the equipment is very likely to have needed to update, re-acquisition. Fifth, conducive to the protection of the safety of drug users In the State Council issued a program in the name of the song provides that in the process of drug use, patients as long as there are adverse reactions or adverse events, you can to the manufacturer or holder or operating companies, to any party to make a claim, the head of the number of the final product quality of the product by the three of them in the end in the holder of the system inside the legitimate rights and interests of the user is maximized. The legitimate rights and interests of the user are maximized protection. MAH Trial Rules Interpretation The trial scope of the drug listing license holder system includes Beijing, Tianjin, Hebei, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong, Guangdong, Sichuan 10 provinces (cities), which in accordance with the overall deployment, the actual introduction of the Beijing and Shanghai, the system is relatively perfect. Key positions Pilot program at the same time there are R & D institutions and R & D personnel can apply for personal, but taking into account the match with the individual, the draft itself mentioned in the key personnel settings, such as quality supervisors staff, safety release of people and other key positions in the final draft of the pilot program are not reflected. Application requirements Beijing requires a residence permit for household registration, but Shanghai only requires a work address. In terms of joint applications, Beijing requires that if more than one individual applies, one person must be elected to be registered as the holder, with a requirement to elect a representative. However, there is no explicit provision for this in Shanghai. Specialty Drugs Beijing requires that specialty drug formulations must be manufactured by companies in the city, and that trustees cannot be located outside of Beijing. Shanghai requires that for sterile supplies, the reverse preparation requirement must be commissioned in Shanghai. Obligations Beijing requires that the holder should sign a quality agreement with the commissioned manufacturer, with the addition of the responsibility to improve the quality of medicines, as well as after the refinement of the evaluation of the responsibility to go public after the recall of these two. Shanghai requires the establishment of a quality management system covering quality-related factors to interface with subsequent production and sales, and there are some very detailed requirements for the establishment of all the specific requirements of the system. In terms of the responsibility of the entrusted producer, Beijing has increased the obligation of the entrusted producer to keep inspection records and archives, and has also stipulated that unauthorized disposal and sale cannot be carried out without the consent of the holder. In terms of supervision and management, the regulatory authorities are required to strengthen the strict pre-market review. Frequently asked questions 1, the holder can not two, three **** with the holders, the holder can not be entrusted with the production of a number of enterprises,
Answer: At present, in order to clarify the main body of the responsibility of the holder can only be one, on a variety can only be a holder. At present, our country's commissioned production methods are not limited to commissioned production can only be entrusted to a, it can be entrusted to a number of.
2, to clarify the joint declaration of more than one applicant, whether it can *** with the same holders of the document number, Answer: The approval number can only be a person. 3, the pilot work of the approval of the main body is the General Administration or the provincial bureau, A: Currently the General Administration acceptance, the National Bureau of approval. 4, the original has been declared clinical APIs and preparations of the varieties now to submit a separate API, increase the supplementary application for listing license holder, whether it can be accepted, the two dosage forms inside a separate application as a raw material listing holder can not, A: Yes, you can. The policy is very flexible. 5, whether the listed varieties are allowed to meet the conditions of the "invisible holder" to change to the legal holder, A: This is the state very much do not advocate, the so-called invisible holders, you legal holders will have to follow the existing varieties and the scope of the provisions of the program to go. 6, production and packaging processes can be entrusted separately, A: We are currently not allowed. Of course, we also put forward, in fact, a lot of our imported sub-packaging, in many imported drugs inside the production and packaging processes are separate, for our listed licensee is not allowed. 7, the domestic establishment of foreign-funded R & D institutions, holding a "Chinese green card" of foreign researchers can become an applicant, Answer: Green card holders are not, but the establishment of foreign-funded institutions is allowed.