China GMP (2010 revision) Compliance

According to the No. 79 of 2011 signed by the Minister of Health of the People's Republic of China, the "Good Manufacturing Practices for Pharmaceutical Production (Revised in 2010)" (hereinafter referred to as the new version of GMP) was reviewed and approved by the Ministry of Health at the Ministry of Health on October 19, 2010. Implemented on March 1, 2011.

China's new GMP has made considerable progress in terms of management and technical requirements compared to the 98 version. In particular, high requirements have been placed on the production of sterile preparations and APIs. The new version of GMP is based on EU GMP, taking into account the domestic gap, with the WHO2003 version as the bottom line.

The new version of GMP certification has two time nodes: the production of sterile drugs such as blood products, vaccines, and injections for pharmaceutical manufacturers should meet the new drug GMP requirements by December 31, 2013; the production of other categories of drugs should be in 2015. The new version of the drug GMP requirements will be reached by the 31st of the month. Enterprises (shops) that do not meet the requirements of the new version of the drug GMP shall not continue to produce drugs after the specified period.

1. What are the new GMP certification materials?

Drug GMP Certification Application (in quadruplicate);

A copy of the Pharmaceutical Manufacturing Enterprise License and the Business License;

Self-inspection of drug production management and quality management (including enterprise profile and historical evolution, production and quality management, and correction of previous certification defects);

Organization chart of pharmaceutical production enterprises (indicating the names, mutual relations, department heads of each department);

Resume of the person in charge of the pharmaceutical production enterprise and the person in charge of the department; the registration form of the pharmacy and related professional and technical personnel, engineering and technical personnel, and skilled workers who have been qualified according to law, and indicate the department and position; the high, middle and junior technicians account for all employees. Proportional situation table;

The full range of dosage forms and varieties of pharmaceutical production enterprises; the scope of application for certification and the variety list (specify the annual production varieties), including the basis of the standard, the drug approval number; the new drug certificate and the production documents and other relevant documents and materials;

Environmental map of the pharmaceutical production enterprise, general layout plan, storage layout plan, layout plan of quality inspection site;

Overview of the pharmaceutical production workshop and the layout of the process layout (including dressing rooms, washrooms, people and logistics channels, air locks, etc., and indicate the level of people, logistics and air cleanliness); air supply, return air, exhaust air of the air purification system Floor plan; plan layout of process equipment;

Apply for a certified process flow or a variety of process flow diagrams, and indicate the main process control points and control items;

Pharmaceutical manufacturer (validation of key processes, main equipment, water system and air purification system in the workshop; verification of inspection instruments, instruments and instruments;

Catalogue of production management and quality management documents for pharmaceutical production enterprises (shops).

2. pharmaceutical companies should evade certification "blocking traffic"

According to the new GMP requirements, the renovation and certification work time of many pharmaceutical manufacturers is tightening.

The new version of GMP certification has two time nodes: the production of sterile drugs such as blood products, vaccines, and injections for pharmaceutical manufacturers should meet the new drug GMP requirements by December 31, 2013; the production of other categories of drugs should be in 2015. The new version of the drug GMP requirements will be reached by the 31st of the month. Enterprises (shops) that do not meet the requirements of the new version of the drug GMP shall not continue to produce drugs after the specified period.

Solid preparations account for a significant portion of the "other categories of drugs." At present, commonly used solid dosage forms include powders, granules, tablets, capsules, pills, films, etc., accounting for about 70% of the pharmaceutical preparations.

Therefore, as the new GMP certification deadline is approaching, the transition period for related companies is actually not much. Taking into account the future development of the company and related work, and avoiding the problem of “clogging” in the certification work, many enterprises have advanced their work of completing the new GMP transformation and certification to more than half a year, which is also encouraged by the relevant departments.

3. correctly understand the new GMP related requirements

Many pharmaceutical companies are increasingly feeling the difficulty of the new GMP certification. Among them, a considerable number of small and medium-sized pharmaceutical enterprises have fewer production lines and lack of risk predictions for regulatory changes. Their plant design and regular renovation and upgrading work have not formed institutional regulations, which have caused long-term transformation tasks before the new GMP deadline. However, the suspension of production is threatened by the loss of the market, and the non-stop production is facing an out-of-stock threat.

Kang Lihua believes that pharmaceutical manufacturers should correctly understand the new GMP requirements. Relatively speaking, the new version of GMP emphasizes software upgrades, and it is not necessary to overthrow old factories and rebuild new ones. In terms of hardware transformation, pharmaceutical manufacturers should conduct comprehensive assessment and decision-making in light of the medium- and long-term development plans of the company and consider factors such as new production varieties in the future.

4. What new concepts are reflected in the new version of GMP compared to the 1998 version?

In the new version of GMP, a new concept of quality risk management was introduced in a timely manner. For example, enterprises were required to establish a quality management system, and risk management should be introduced in quality management, emphasizing that science and risk should be based on the implementation of GMP.

There are risks such as pollution, cross-contamination, confusion and errors in the pharmaceutical production process. It is not possible to find problems by inspection in accordance with quality standards and must be controlled in the production process. Therefore, the new version of GMP introduces the concept of risk management and correspondingly adds a series of new systems, such as: supplier audit and approval, change control, deviation management, over-standard (OOS) investigation, corrective and preventive measures (CAPA), continuous Stability inspection plan, product quality review and analysis, etc., from the procurement of raw materials, production process changes, deviation treatment in operation, investigation and correction of problems found, continuous monitoring of drug quality after listing, etc. The management and control of risks encourages production enterprises to establish a comprehensive chain and corresponding systems, timely identify unsafe factors affecting the quality of drugs, and proactively prevent the occurrence of quality accidents to maximize the quality of finished products and listed drugs.

Second is the introduction of a new concept of quality management system. The new GMP clearly requires pharmaceutical companies to establish a comprehensive, systematic and rigorous quality management system, and must be equipped with sufficient resources, including human resources and management systems, to ensure the effective operation of the quality system.

In the past, many people's awareness, quality management and implementation of GMP is a matter of quality management departments and quality management personnel. The new version of GMP reflects the concept of full participation in quality, emphasizing the quality responsibility of senior managers such as legal persons and corporate leaders, including quality leaders and quality attorneys, making the quality management of pharmaceutical manufacturers more comprehensive. This is the further implementation of “Enterprises are the first responsible person for drug quality” and embodies the modern enterprise management concept of institutionalized management.

5. What are the characteristics of the new version of GMP? Compared with the 1998 version, what requirements have been greatly improved? What new requirements have been added?

The new GMP provisions are more specific, instructive and operability; the regulations on production conditions and management systems are more comprehensive and specific, and the safety, stability and uniformity of drug quality are further ensured from the production chain.

The characteristics of the new version of the drug GMP are first reflected in the strengthening of software requirements. First, the construction of a quality management system for pharmaceutical production has been strengthened, and the requirements for quality management software for enterprises have been greatly improved. The requirements for constructing a practical and effective quality management system are refined, and the control and management of key links in pharmaceutical production are strengthened to promote the improvement of the quality management level of enterprises. The second is to comprehensively strengthen the quality requirements of employees. The terms and contents of the quality requirements for quality management personnel in pharmaceutical production have been added to further clarify responsibilities. For example, the new version of the drug GMP clarifies that the key personnel of the pharmaceutical manufacturing enterprise include the qualifications and duties that must be performed by the person in charge of the enterprise, the person in charge of production management, the person in charge of quality management, and the quality attorney. The third is to refine the document management regulations such as operating procedures and production records, and increase the guidance and operability.

In terms of hardware requirements, the new GMP has raised the standard for some production conditions. One is to adjust the cleanliness requirements of sterile preparations. In order to ensure the quality and safety of sterile drugs, the new version of GMP adopts the latest classifications of WHO, EU and A, B, C and D in the sterile drug appendix, and puts forward specific requirements for the cleanliness level of aseptic drug production; The requirements for on-line monitoring, in particular the static and dynamic monitoring of suspended particles, that is, suspended particles in the production environment, provide detailed regulations for the monitoring of planktonic bacteria, sedimentation bacteria (microorganisms in the production environment) and surface microorganisms.

In addition, the requirements for equipment and facilities have been increased. Design and layout requirements for plant facilities, storage areas, quality control areas and auxiliary areas; equipment design and installation, maintenance and repair, use, cleaning and status identification, calibration, etc. Specific provisions.

6. How are the regulatory requirements for the new version of GMP and drug registration approval, drug recall, and adverse reaction monitoring effectively linked?

The new version of GMP emphasizes effective linkage with other regulatory links such as drug registration, drug recall, and adverse drug reaction monitoring.

The production quality management process of pharmaceuticals is the implementation and embodiment of the registration approval requirements. The new version of GMP emphasizes the consistency of production requirements and registration approval requirements in several chapters such as “production management”, “quality management”, “commissioned production and commissioned inspection”.

The new version of GMP also pays attention to the connection with the "Administrative Measures for Drug Recall", stipulating that enterprises should formulate recall operation procedures, designate special personnel to organize and coordinate recall work, and urge enterprises to follow the provisions of the "Administrative Measures for Drug Recall", once the quality of the drugs appears after listing. Or the phytotoxic event, you can recall all the problem drugs in the first time to avoid new hazards.

For the monitoring of adverse drug reactions, there are relevant provisions in the 1998 edition of GMP, but the regulations are simple. In the new version of GMP, it is clearly stipulated that enterprises should establish an adverse drug reaction report and monitoring management system, actively collect adverse reactions, and set up specialized agencies and full-time personnel to manage. These requirements are consistent with the requirements of the “Adverse Drug Reaction Reporting and Monitoring Management Measures” that are being revised and will be promulgated and implemented.

7. What is the significance of implementing the new version of GMP to promote industrial restructuring and transform growth?

From the perspective of long-term healthy development of the industry, the implementation of the new version of GMP is conducive to promoting the structural adjustment of China's pharmaceutical industry and enhancing the international competitiveness of China's pharmaceutical production enterprises, and accelerating the entry of Chinese pharmaceutical products into the international market.

The existing raw material medicines and preparations production enterprises in China show a pattern of multiple, small, scattered and low overall, with low production concentration and insufficient independent innovation capability. The implementation of the new version of GMP is in line with the requirements of the national strategic emerging industry development and transformation of economic development mode, which is conducive to promoting the concentration of pharmaceutical industry resources to advantageous enterprises and eliminating backward productivity; it is conducive to adjusting the medical economic structure to promote industrial upgrading.

The implementation of drug GMP is a process to improve the quality and safety of drugs, and is also a process to promote the gradual progress of China's pharmaceutical production enterprises to the international market. Because the revised GMP standards for drugs in 1998 are different from the international advanced standards, it has greatly affected the entry of Chinese pharmaceutical products into the international market. This revision is basically consistent with the WHO Pharmaceutical GMP in terms of technical requirements. After full implementation, it will help the export pharmaceutical manufacturers to generally meet the standards recognized by the international community, help to cultivate internationally competitive enterprises, and accelerate the entry of Chinese pharmaceutical products into the international market. .

In the next step, the National Bureau will strengthen cooperation with the International Drug On-site Inspection Convention and promote international mutual recognition of GMP certification.

8. How to effectively plan the investment in technological transformation funds when implementing the new version of GMP?

Due to the improvement of the overall standard, the newly revised drug GMP does require the company to invest certain funds for technical transformation. For example, the improvement of GMP software requires corresponding investment; in order to improve the quality of employees, enterprises need to increase training costs; in order to strengthen software management, enterprises need to increase management personnel, which will increase wages; the improvement of GMP hardware for sterile drugs will increase enterprises. Manufacturing costs and more.

For the investment in technological transformation, the investment is different because of the different foundations of different enterprises and different production varieties. From the perspective of various segments, hardware investment is mainly concentrated on sterile drugs, especially freeze-dried powder injections without final sterilization, and the level of sterility assurance in the production process must be improved. Other products that do not require sterility, such as oral preparations, do not substantially involve hardware modifications.

9. How can enterprises grasp and implement the new version of GMP faster and better?

Pharmaceutical manufacturers are the main body of implementation of pharmaceutical GMP. In order to ensure the implementation of the newly revised drug GMP, drug manufacturers should, in accordance with their actual conditions, combine product structure adjustment and industrial upgrading, formulate implementation work plans, actively organize the study and training of enterprise employees, and complete the necessary softness within the prescribed time limit. , hardware upgrades and technical transformations, apply for inspection and certification in advance in accordance with the new revised reporting requirements.