Food and Drug Administration Chemical Tube [2017] No. 68
Beijing, Tianjin, Hebei, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong, Guangdong, Sichuan (city) Food and Drug Administration:
According to the Standing Committee of the National People's Congress, the “Decision on Authorizing the State Council to Launch the Drug Listing Permit Holder System and Relevant Issues in Some Places” and the “Notice on the Pilot Program for Printing and Approving the Drug Licensing Holder System of the General Office of the State Council” [2016] No. 41), the Food and Drug Administration has organized a pilot program for the holders of drug marketing licenses (hereinafter referred to as holders). Since the pilot work began, the pilot provinces (cities) have successively introduced implementation plans, actively carried out work and achieved phased results, but there is still a gap between the overall work progress and actual requirements. In order to speed up the pilot work of the holder system, further explore the rights and obligations and legal responsibilities of the holders, the quality management system in the production and the responsibility system for the production and sales of the entire chain, the inter-regional drug regulatory agency supervision, the division of responsibilities and the responsibility For matters such as landing, the relevant matters in the pilot are as follows:
1. Implement the legal liability of the holder. The holder is responsible for the whole chain of drug production and sales and the whole life cycle management of the drug, and assumes full legal responsibility for preclinical research, clinical trials, manufacturing, distribution and distribution, and adverse reaction monitoring. Pharmaceutical manufacturers, drug research and development institutions and scientific research personnel can be the holders. A pharmaceutical production and processing enterprise that does not hold a drug approval number but has a drug production license may be entrusted with the production and processing of drugs. Units and individuals entrusted by the holder to conduct research and development, clinical trials, manufacturing, sales and distribution shall be responsible for the responsibilities and agreements stipulated by laws and regulations. The holder is responsible for the listing and release of the products, and is fully responsible for the quality of the drugs sold on the market. The entrusted production enterprises are responsible for the production according to the agreed process and quality standards, responsible for the production release of the products, and bear the corresponding quality responsibility for the holders. The entrusting party and the entrusted party shall sign a specific entrustment agreement to clarify the rights and obligations of the technical requirements, quality assurance, and division of responsibility entrusted by both parties in production.
Second, integrate technical resources and promote specialized large-scale production. The pharmaceutical production enterprise group company can concentrate the drug approval number of each holding subsidiary to the group company and become the holder. The group company integrates and integrates the products according to the production and processing capabilities of each holding subsidiary, so that each subsidiary becomes a production base with characteristics, advantages and scale. The group company implements a unified quality management system for each subsidiary, and the group company The quality of the products listed is fully responsible. The drug approval number held by the group company shall be reviewed by the provincial food and drug supervision department at the place where the transferee is located, and reported to the Food and Drug Administration for approval. The food and drug supervision department at the place where the product is transferred shall provide support.
Where the drug production and processing site is relocated or the workshop is relocated, the drug approval number may be retained in the original enterprise. The production management, technical standards, and product quality are consistent with the original production enterprise, and are produced by the newly-built production and processing enterprise or production workshop. After the overall relocation or the overall relocation after the merger, the original enterprise becomes the holder, and the holder submits the application for acceptance, technical review, on-site inspection, sample inspection, etc. to the provincial food and drug supervision department where the production enterprise is located, and is located by the local The provincial food and drug supervision department shall report to the Food and Drug Administration for the record (the biological products shall be reported to the Food and Drug Administration for technical review and administrative examination and approval). The on-site inspection of the registered production of the pilot varieties was carried out in conjunction with the on-site inspection of the “Good Manufacturing Practices” (Drug GMP) certification.
The manufacturing enterprise to which the drug research and development institution belongs may transfer the drug approval number to the drug research and development institution, and the drug research and development institution as the holder to commission the production.
When applying for the above adjustments, the enterprise shall, in accordance with the relevant provisions of the food and drug supervision department, truthfully submit the registration of the complete product files such as the drug prescription, production process, raw and auxiliary materials and quality standards to the Food and Drug Administration.
Third, the holder is allowed to commission more production. The holder needs to establish a drug quality management system. Under the premise of ensuring the consistency of drug quality and efficacy, the holder is allowed to apply for entrusting multiple enterprises to produce and process. After the holder is approved for the first production, he can entrust other production enterprises to produce and process. The drugs to be processed must have the same prescription, process and quality, and the holder bears full legal responsibility. For the pilot varieties that approve multi-point production, a drug approval number is issued in the drug approval document, which lists the name and production address of the relevant entrusted production enterprise, and the specific manufacturer name and production address are indicated in the drug label and instruction manual. And other information. Pharmaceutical production and processing enterprises must strictly implement the relevant provisions of the drug GMP and accept the inspection and supervision of the regulatory authorities.
4. Allow the holder to sell the medicine on its own or by commission. Drug research and development institutions and scientific research personnel as holders may sell drugs on their own, but should have the ability and conditions for drug management as stipulated in the Drug Administration Law. It is also possible to entrust a pharmaceutical manufacturer that produces it or a pharmaceutical company that has a drug business license to sell the drug. When entrusting the sale of drugs, they shall sign an entrustment contract, clarify their respective rights, obligations and responsibilities, abide by relevant laws and regulations, and implement drug traceability and quality management responsibilities. The holder must master the quality information and adverse reactions during the circulation of the drug, recall the drug when quality problems occur, and control it in time. All pharmaceutical enterprises must strictly implement the relevant requirements of the "Good Manufacturing Practices" (drugs GSP) and improve the quality management system and risk control system of the circulation.
V. Accelerate the review and approval of the registered enterprises for the registered varieties. For the application for the listing of the pilot varieties to be commissioned for production selected by the provinces required by this notice, it is in line with the Opinions of the Food and Drug Administration on the Implementation of the Priority Review and Approval of the Backlog of Drug Registration Applications (Food and Drug Administration Chemicals [2016] No. 19 The applicant may submit an application, and the Drug Evaluation Center of the State Food and Drug Administration will be included in the priority review and approval. The development site verification, clinical trial data verification, production site inspection, sample inspection and drug GMP certification shall be submitted together. Priority is given.
In the evaluation of the quality and efficacy consistency of generic drugs, the holder of the drug approval number can apply to become the holder when submitting the application for consistency evaluation. The Food and Drug Administration has clearly approved the holders while approving the consistency assessment.
6. The holder shall carry out pharmacovigilance and annual reports. The holder should establish a pharmacovigilance system. The holder shall carry out monitoring of adverse drug reactions in accordance with the relevant requirements of the Measures for the Reporting and Monitoring of Adverse Drug Reactions, continue to examine the safety and effectiveness of drugs after listing, and adopt timely risk control measures for drugs with identified risks. Report clinical adverse reactions and disposal measures to the food and drug regulatory authorities. The holder may cooperate with the relevant third party to entrust him to carry out the pharmacovigilance of the pilot variety, but does not exempt the holder from the obligations and responsibilities.
Within 20 working days after the end of each year, the holder reports to the Food and Drug Administration that the production, sales, prescription, process, pharmacovigilance, quality control measures, etc.
7. Pharmaceutical production enterprises in the pilot area may refer to the pilot content management. A pharmaceutical production enterprise holding a drug approval number may apply to participate in the pilot commissioned by the holder, and shall comply with the relevant provisions of the holder after the approval of the provincial food and drug supervision department. The trial effect of the commissioned production of the drug can be included in the work summary of the license holder.
8. Improve the responsibility for drug supervision in the two places. The food and drug regulatory agencies commissioned by the two regions should be well supervised. The provincial food and drug supervision department at the place where the listing permit holder is located shall supervise the act of entrusted production and the management of the post-marketing products by the holder. The food and drug regulatory agencies at the place where the production is entrusted shall supervise the production process and product quality. In the event of product quality problems or serious adverse reactions, the regulatory authorities of the two places shall coordinate and jointly investigate and deal with them.
9. Actively explore the pilot model. The food and drug supervision departments of the pilot provinces (municipalities) shall combine local drug production enterprises and drug research and development institutions on the basis of the “Pilot Program for Drug Listing License Holder System” (Guo Ban Fa [2016] No. 41) and the requirements of this notice. The actual situation of scientific research personnel, and actively explore the pilot model that is in line with the actual situation of the province (city). The food and drug regulatory authorities of the pilot provinces (municipalities) selected a number of applicants as their respective pilots, and explored pilot projects for various modes such as new drugs, consistency evaluation, overall relocation, and entrusted production (excluding the holder's own production). Report the selection of pilots to the Food and Drug Administration before August 30, 2017.
X. Summarize the pilot experience in a timely manner. The goal of the pilot is to establish a perfect responsibility system for the rights and obligations of the holders and trustees, establish a comprehensive supervision and inspection responsibility system and quality assurance system for cross-regional supervision, and form a complete system for listing license holders. The food and drug supervision departments of the pilot provinces (municipalities) shall promptly carry out the pilot work according to this requirement, and submit the mid-term summary of the pilot work in December 2017. The General Administration of Food and Drug Administration will strengthen guidance on the pilot work, supervise and inspect the progress of the pilot work, and promptly promote the experience gained in the pilot work. If the work is not effective, the Food and Drug Administration will notify the situation as appropriate.
Food and Drug Administration
August 15, 2017