How should the R&D institutions under the drug marketing license holder system be transformed?

Medical Network January 12

History background

The Medicine Authorization Holder (MAH) system is a drug management system commonly practiced in developed countries such as Europe, the United States, and Japan. The essence of the marketing authorization system that is separate pharmaceutical production license, permit in addition to pharmaceutical production enterprises, research institutes and R & D staff can also act as marketing authorization holders to obtain drug approval number, and can delegate manufacturers produce drugs.

At the end of 2001, the EU issued guidelines for the marketing of drugs for human use, and proposed a market access system for the separation of “MAH” and “PLH”. The US listing license is similar to the EU, but not exactly the same. The US drug market is divided into two stages: clinical trial application and listing application, while the EU implements a centralized review system. Applicants only need to submit a listing application to the EMA. The application materials include preclinical research data and clinical research data. Compared with Europe and the United States, Japan proposed the MAH qualification access system in 2005, that is, only after obtaining the MAH qualification, can the application for listing of drugs be submitted, and at the same time, it is required to establish three qualified full-time managers, namely the general manager and the quality. Guarantee supervisor, listed safety control supervisor.

China has always implemented a management model for the merger of drug marketing licenses and production licenses. Drug R&D institutions/persons cannot obtain drug approval documents, and only allow drug manufacturers to have drug approval numbers. R&D institutions can only use related drugs if they obtain new drug certificates. Technology transfer to pharmaceutical manufacturers. This model is not conducive to mobilizing the innovation enthusiasm of the research institutions/personnel, is not conducive to industrial restructuring and resource optimization, and is not conducive to suppressing low-level repetitive investment and construction. However, starting from the second half of 2015, with the introduction of a series of laws and policies of the MAH system, it is believed that the above phenomena will be effectively alleviated and improved.

Potential impact on the Chinese pharmaceutical industry

Although the MAH system is still in the trial stage in China, there are still many uncertainties, but the newly released Drug Registration Management Measures (Revised Draft) and the "Drug Administration Law Amendment (Draft for Comment)" all indicate this system. It will eventually be carried out nationwide. This also indicates that this system will bring huge changes to the pharmaceutical industry.

1. Inspire innovation and enthusiasm, refine the division of labor, optimize resource allocation

For R&D institutions/persons, under the MAH system, the drug approval number can be held as a marketing license holder, and the pharmaceutical production enterprises can be entrusted to the production and sales enterprises for sales, thereby obtaining direct benefits and enhancing the research and development power of the enterprise. Drive the enthusiasm of research and development personnel. Rather than the former R&D institutions or personnel can only transfer technology to the production enterprise, or can only passively sign the benefit distribution agreement with the pharmaceutical production enterprise, not only the intellectual property rights of the R&D personnel are not effectively protected, but also the benefits they deserve. Get protection.

Under the MAH system, the production enterprise can also be the license holder of the listing, and the manufacturer can be selected in a targeted manner, and the entrusted production enterprise can use its own resource advantages to carry out customized production/processing, that is, what we call CMO enterprises. Like the production companies, drug sales companies can also use their rich market experience, mature sales channels and other resources to undertake the sales entrustment of the license holders on the drugs. This flexible mode of “professional people doing professional things” will spawn a group of enterprises with core competitiveness, and at the same time make the division of labor more detailed and optimize resource allocation.

2 , speed up the application of new drugs, saving time costs

Under the MAH system, if the technical review time is not included, the clinical declaration of the new drug can be shortened from the previous 117 to 127 days to 14 days; if the technical review time is included, it will be shortened from the original 12 to 18 months to 9.5 months. Significantly accelerate the listing process of new drugs. At the policy innovation meeting of the 9th China Pharmaceutical Entrepreneur Scientists Investors Conference, Li Fang, deputy director of the CFDA Pharmaceutical Registration Division, said, “Since the pilot of the MAH system in June 2016, as of the end of July 2017, 10 A total of 987 drug registration applications were accepted in the pilot provinces and municipalities, of which 450 were MAH applications, accounting for 45.6%. The specific data is as follows:

3. Improve the legal system and insurance system

The “Pilot Program for Drug Listing License Holder System” emphasizes MAH's ability to assume responsibility for safety throughout the life cycle of the drug, and clearly states that MAH needs to “commit to submit to the provincial drug regulatory authority before the drug is marketed. A security agreement with a guarantor or an insurance contract with an insurance institution." At present, with the continuous advancement of the MAH system, supporting laws and regulations will be established, and the insurance industry has also introduced professional insurance for MAH. Through the establishment of a sound legal system and insurance system, the professional evaluation of MAH makes it possible to restrict the interests of patients while restraining MAH.

4. Attracting capital investment

China's huge population size, aging, neonatal policies, and economic growth have created a huge market that has made capital eager to try. The number of investment institutions currently focused on investment in the medical field is increasing rapidly. According to statistics, in 2017, there were more than 262 investment institutions specialized in investing in the medical and health industry, twice as many as five years ago. New drug research and development as an emerging field has become a hot spot for investment.

Make full use of the MAH system

From the second half of 2015 to the present, the State Food and Drug Administration has introduced a series of measures, including clinical data verification, priority review, consistency evaluation, MAH system and other policies, which clearly reflect the government's views on the industry and the will to reform. That is, we hope that through policy guidance, drugs will return to the essence of their treatment, improve quality, value clinical value, and pay attention to the cost-effectiveness of drugs; let the industry environment be rational and standardized. The status quo of the industry is expected to change, and companies that focus on R&D and quality will stand out.

Under the MAH system, the concept change of R&D institutions is particularly important, and it is necessary to control the quality and safety of products after they are put on the market.

(1) R&D institutions need to establish a complete and reasonable quality management system and drug safety monitoring system to pay more attention to the clinical value of patients and drugs.

(2) Accurately position itself in the process of innovation and R&D, and strengthen the sense of responsibility of the company.

(3) Actively adopt an open cooperation model and establish cooperative relationships with CRO (contract research organization), CMO (contract production organization), and CSO (contract sales organization) to reduce costs and spread risks.

Undoubtedly, the MAH system will greatly enter the technological innovation of the pharmaceutical industry in China, improve the quality system, improve and perfect the relevant legal system and insurance system, optimize the resource allocation of the industry, strengthen the division of labor and specialization, and attract more Venture capital has laid a solid foundation for China to become a major pharmaceutical innovation country.