Strengthen relevant regulations for supervision and management of medicinal excipients

Food and Drug Administration (Drugs and Drugs Supervision Bureaus) of provinces, autonomous regions, and municipalities directly under the Central Government:

In order to further strengthen the production and use management of pharmaceutical excipients and ensure the quality of medicines, the State Food and Drug Administration organized and formulated the “Regulations on Strengthening the Supervision and Administration of Pharmaceutical Excipients” in accordance with the Laws and Regulations of the People's Republic of China on Drug Administration and its implementing regulations. Provisions. Now that you are issued and issued, please supervise relevant enterprises in the administrative region to comply with the implementation and do a good job of supervision and inspection.

State Food and Drug Administration Aug. 1, 2012 Relevant regulations for strengthening the supervision and management of medicinal excipients Medicinal excipients are an important part of drugs and directly affect the quality of drugs. In order to further strengthen the supervision of production and use of pharmaceutical excipients and ensure the quality and safety of pharmaceuticals, it is based on the "People's Republic of China Drug Administration Law" and its implementing regulations, "Special Provisions of the State Council on Strengthening Food Safety Supervision and Administration," and "Pharmaceutical Production Supervision." The relevant laws, regulations and rules, such as the Administrative Measures, Drug Registration Management Measures, and Drug Manufacturing Quality Management Regulations, are stipulated as follows:

I. Pharmaceutical preparation enterprises must ensure the quality of purchased pharmaceutical excipients. (1) Pharmaceutical preparation manufacturers are responsible for drug quality. It is imperative to strengthen the management of pharmaceutical production quality and ensure the quality and safety of pharmaceuticals. It is necessary to strictly manage the use of pharmaceutical excipients, and to use the pharmaceutical excipients that meet the requirements to produce pharmaceuticals in accordance with the prescription process approved by the drug regulatory authority. The drug manufacturer must bear the main responsibility for any drug quality problems caused by illegal use of medicinal auxiliary materials.

(2) Pharmaceutical preparation manufacturers must improve the quality management system. It shall ensure that the quality management department effectively fulfills the duties of quality assurance and quality control, and that the person-in-charge of the company and the personnel of other departments shall not interfere with or impede the quality management department from performing its duties. It was determined that the pharmaceutical excipient supplier should conduct an audit and be approved by the enterprise quality management department.

(3) The manufacturer of pharmaceutical preparations shall strengthen the audit of suppliers of medicinal excipients. In accordance with the relevant requirements of the “Quality Control Practice for Pharmaceutical Production (2010 Revision)”, the quality assessment of pharmaceutical excipient manufacturing enterprises shall be conducted regularly, quality audits and retrospective analysis shall be conducted on the quality system of pharmaceutical excipient manufacturing enterprises, and all purchased drugs shall be established. Use accessories and suppliers' quality files.

(4) The manufacturer of pharmaceutical preparations must strictly control the quality of the medicinal excipients used. All purchased pharmaceutical excipients must be inspected in accordance with the quality standards approved at the time of approval of registration of pharmaceuticals to ensure compliance with pharmaceutical requirements. For pharmaceutical excipients that have been issued national drug standards, they must meet the requirements of the national drug standards.

(5) The manufacturer of pharmaceutical preparations shall sign quality agreements with the suppliers of major pharmaceutical excipients. Keep abreast of the changes in the use of pharmaceutical excipients, study and assess the impact of changes on the quality of the drug, and report in accordance with the "Drug Registration Regulations" requirements.

Second, pharmaceutical excipients manufacturers must ensure the quality of the product (6) pharmaceutical excipients must be responsible for product quality. Strict implementation of the “Quality Control Specification for Pharmaceutical Excipients” should be followed to improve the quality management system of enterprises, strengthen the audit of suppliers of raw materials used for production, strictly control the quality of raw materials, organize production according to the prescription process for product registration approval, and standardize the preparation of product batch numbers. Ensure product quality and stability. For medicinal excipients that have not obtained the approval number and have been used historically, they should organize production in accordance with the quality agreement agreed with the pharmaceutical preparation enterprise contract.

(7) Pharmaceutical excipient manufacturers must ensure product quality. Each batch of products shall be subject to full-scale inspection according to the quality standards agreed in the registration or approved by the manufacturer of the pharmaceutical preparations. Qualified products may be stored and sold. For pharmaceutical excipients that have been enacted national drug standards, they must meet the relevant requirements of the national drug standards. Before product release, all production documents and records, including inspection data, should be reviewed by the quality management department and meet the requirements. If they do not meet the requirements, they must not be released.

(8) The manufacturer of medicinal excipients shall cooperate with pharmaceutical preparation enterprises to conduct supplier audits. If changes in the quality of pharmaceutical excipients, such as production processes and sources of raw materials, may occur, they should actively carry out appropriate assessments and promptly notify pharmaceutical product manufacturers.

Third, the drug supervision and administration department implements classified management of medicinal auxiliary materials. (9) The pharmaceutical auxiliary materials are classified and managed. The new pharmaceutical excipients and pharmaceutical excipients with higher safety risks are subject to license management, that is, production enterprises should obtain the “Drug Production License”, and the varieties must obtain a registered license; the other filing materials should be subject to record management, that is, production enterprises and their products. Make a record. The list of varieties under license management is organized by the State Food and Drug Administration and published in batches.

For pharmaceutical excipients that are subject to license management, production enterprises should submit relevant materials as required. The provincial drug supervision and administration department shall conduct on-site inspection, dynamic sampling inspection according to the requirements of the "Quality Management Practice for Pharmaceutical Excipients Production", and be registered after passing the examination by the State Food and Drug Administration. The State Food and Drug Administration shall review the application for the registration of excipients with the corresponding pharmaceutical preparations.

For pharmaceutical excipients that are subject to record management, relevant information shall be submitted by the manufacturer and reported to the local drug regulatory agency at the locality for the record. Provincial drug supervision and administration departments may perform on-site inspections and sampling inspections as required.

The relevant requirements for licensing and filing of medicinal excipients are formulated separately. Imported pharmaceutical excipients are referred to this provision and reported to the State Food and Drug Administration for approval or filing.

(10) Strictly apply for pharmaceutical excipients in drug registration applications. When a pharmaceutical preparation company applies for registration of a drug, it shall submit information on the types of pharmaceutical excipients used, suppliers, quality standards, and audit results of suppliers, etc., and shall make corresponding research and submit research on supplementary applications for changing the types of medicinal auxiliary materials. The data and supplier audit results can be used only after being approved by the State Food and Drug Administration; if only the supplier is changed without changing the type of accessories, relevant research materials and audit results of the supplier must be submitted and filed with the provincial drug regulatory authority. be usable.

(11) To strengthen the management of pharmaceutical excipients standards. The State Food and Drug Administration organizes the National Pharmacopoeia Commission to work on the revision of the quality standards for pharmaceutical excipients, publish national pharmaceutical standards for pharmaceutical excipients, and study and formulate recommendations for pharmaceutical excipients. Pharmaceutical supervisory and administrative departments at all levels conduct supervision and inspection in accordance with national drug standards.

4. The drug supervision and administration department must strengthen the supervision of the whole process of the production and use of medicinal excipients. (12) The local drug supervisory and administrative departments at various levels should implement the supervision responsibility. It is necessary to strengthen the day-to-day supervision of pharmaceutical preparation enterprises within its own administrative region, and focus on checking whether the pharmaceutical preparation production enterprises produce according to the approved process prescriptions; whether or not to audit the pharmaceutical auxiliary materials production companies according to the requirements of suppliers' audit; whether they are used as required. The pharmaceutical excipients were tested according to the corresponding quality standards; whether the pharmaceutical excipients were changed without approval; if the suppliers were changed, they were filed as required.

(13) Local drug regulatory agencies at all levels should strengthen the supervision of production of medicinal excipients. The company conducts daily supervision of pharmaceutical excipients manufacturing enterprises within its administrative area, or conducts extended inspections on pharmaceutical excipients manufacturing enterprises based on problems found in the supervision and inspection of pharmaceutical preparation manufacturers. Focus on checking whether the production of pharmaceutical excipients complies with the "Quality Control Practice for Pharmaceutical Excipients"; whether strict control over the quality of raw materials; whether to follow the approved or documented process for production; whether to establish a perfect batch number management system and factory inspection system. For those who do not accept inspections, pharmaceutical product manufacturing enterprises may not use the pharmaceutical excipients they produce.

(14) Drug regulatory agencies at all levels shall strengthen the supervision and inspection of medicinal excipients. According to the situation of supervision and inspection, the focus of sampling inspection shall be clarified, and the scope and requirements of sampling shall be clarified. Sampling inspection scope shall cover the use units of pharmaceutical auxiliary materials such as pharmaceutical excipients manufacturing enterprises and pharmaceutical preparations manufacturing enterprises. Enterprises and institutions that have found problems in past supervision and inspections and random inspections shall increase the frequency and intensity of random inspections.

(15) Drug regulatory agencies at all levels must intensify investigation and punishment. It is found that pharmaceutical manufacturing enterprises and pharmaceutical excipient manufacturing enterprises that violate laws and regulations in the production and use of pharmaceutical excipients shall be subject to the "People's Republic of China Drug Administration Law" and "Special Provisions of the State Council on Strengthening Food Safety Supervision and Administration" and other related issues. It is stipulated that relevant enterprises and responsible persons shall be investigated and dealt with. If the circumstances are serious, they shall be severely and severely dealt with according to law. If a crime is constituted, it shall be transferred to the public security organ and the criminal liability shall be investigated according to law.

V. Pay attention to basic data construction and establish a credit management mechanism (16) Establish a database of pharmaceutical excipients. Pharmaceutical preparation enterprises shall, according to the use of medicinal excipients approved by the drug supervision and administration department, fill in the information on the use of pharmaceutical excipients in the product category, and notify and assist pharmaceutical excipients production enterprises to fill out the production information of pharmaceutical excipients and report to their respective provincial level Drug supervision and management department. The State Food and Drug Administration and provincial drug supervision and administration departments collected relevant information, established a database of pharmaceutical excipients, and fully grasped the dynamics of production and use of medicinal excipients.

(17) Establish a credit file for pharmaceutical excipient manufacturing enterprises. Each provincial drug regulatory agency shall establish a credit file for pharmaceutical excipient manufacturing enterprises to publicly inspect and sample the pharmaceutical excipients production companies for reference when pharmaceutical preparation manufacturers select pharmaceutical excipients.

(18) Encourage the public to participate in supervision and management. Support industry associations, third-party agencies and the public to supervise and report violations of laws and regulations in the production and use of pharmaceutical excipients to jointly maintain the quality and safety of pharmaceuticals and pharmaceutical excipients. The relevant industry associations should strengthen industry self-discipline, promote the integrity of the industry, promote classified management, and guide the regulation of the production of pharmaceutical preparations and pharmaceutical excipients.

This regulation shall be interpreted by the State Food and Drug Administration and shall be implemented as of February 1, 2013.