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Historical evolution and future trend of GCP guidelines at home and abroad
GCP is the abbreviation of Good Clinical Practice, which is the quality management standard of drug clinical trials. GCP is a standard law that regulates the whole process of drug clinical trials, including scheme design, organization and implementation, supervision and inspection, recording, analysis, summary and report, and it is an international ethical and scientific quality standard. GCP is not only suitable for people who undertake clinical trials in different stages (I-IV) (including hospital administrators, members of ethics committees, experts, professors, doctors, pharmacists, nursing staff and laboratory technicians), but also suitable for drug supervision and management personnel, clinical researchers in pharmaceutical enterprises and related personnel.

At present, the internationally accepted GCP is ICH-GCP, while China implements China GCP promulgated by CFDA.

ICH stands for International Coordinating Committee. According to the content of the coordination meeting, it is the "International Coordination Meeting on the Technical Requirements for the Registration of Medicines for Human Use". Since the establishment of ICH 1990, many guidelines have been issued, including quality Q, effectiveness E, safety S and multidisciplinary M ... Among them, the effectiveness E series includes the design, implementation, safety and report of clinical trials, and also covers more than 20 guidelines such as new biotechnology-derived drugs and targeted drugs produced by pharmacogenetics/genomics technology. E6 in E series is an ICH-GCP file.

*EWG/IWG indicates that this version is being revised and has not been officially released and implemented.

? 65438+1 May 19961day, ICH GCP(R 1) guide was approved.

? 20 16 1 1.9, the latest revised version of ICH E6(R2) was released, which is also the current ICH-GCP guide.

? 20 1 9 From June/kloc-0 to June 6, 2009, the conference was held in the Netherlands, and ICH-GCP entered a new revision cycle R3 (ICH E6(R3)EWG in E-series documents is being revised on behalf of the expert working group).

The guideline issued on 20 16 is the first revision since 1996 was formulated in May. The purpose of the revision is to encourage the use of more advanced and efficient methods in the design, organization, implementation, monitoring, recording and reporting of clinical trials, such as computerized systems, risk-based quality management systems and centralized monitoring, so as to ensure the rights and interests of subjects and the quality of clinical trial data.

The ICH E6(R2) guideline does not modify the original structure and text, but adopts the form of supplementary clauses, adding 26 clauses in total, covering 6 chapters, including general principles, terminology explanation, GCP principles, researchers' responsibilities, sponsors' responsibilities and clinical trial preservation documents.

ICH held a meeting in Amsterdam, the Netherlands from June/KLOC-0 to June 6, 1965. About 500 members of 16 ICH and 28 observers attended the meeting. In the minutes of the meeting subsequently released by ICH, it was clearly stated that ICH-GCP entered a new revision cycle R3, and the revision schedule of R3 was published in ICH official website.

R3 being revised will be a comprehensive revision of ICH E6(R2) guide, and its revision objectives include: 1. In order to solve the application problems of GCP principles in increasingly diverse clinical trials, such as clinical trials initiated by researchers and real-world clinical trials, new E6 guidelines will be formulated; 2. Solve the problem of data source management supporting supervision and medical decision-making; 3. Promote the rational application of new technologies in clinical trials; 4. Solve the complex clinical trial problems in the current global regulatory environment.

The EWG (Expert Working Group) participating in the revision includes experts from different disciplines, including clinical, statistics, data science, clinical outcome evaluation, regulatory compliance and other potential disciplines.

ICH E6(R 1) will be implemented on 1996, and E6(R2) will be implemented on 20 16. According to the current schedule of R3, the waiting time is not expected to be very long.

? After 1996 ICH approved ICH-GCP guidelines, China's GCP guidelines were born and developed continuously:

1On March 2, 998, the Ministry of Health of China issued the "Management Standard for Drug Clinical Trials" of China (for Trial Implementation).

1 September, 9991day, the State Administration of Pharmaceutical Products (SDA) issued the Management Standard for Drug Clinical Trials.

? On August 6th, 2003, the State Food and Drug Administration of the United States (SFDA) issued the Quality Management Standard for Drug Clinical Trials (GCP), which came into effect on September 6th, 2003. This version of GCP is also the GCP of China now.

? 2065438+In February 2005, China Food and Drug Administration (CFDA) published the first fine-tuning revised version for comments.

? Following the publication of ICH-GCP(R2) on 201/ich, China CFDA published the second draft of GCP on 20 16 and 12, which echoed the latest revision of ICH-GCP. On June 2065438+2007 1, China CFDA joined ICH, so it is more necessary to revise GCP. 2018 July 17 The third GCP (revised draft for soliciting opinions) was released, and it is still in the stage of soliciting opinions.

GCP of China was compiled on the basis of ICH-GCP and combined with the actual situation in China. Basically in line with international standards, basically feasible; It not only conforms to the basic spirit of international GCP, but also conforms to the drug management regulations of China. In written form, it complies with the laws and regulations of China, GMP and GLP.

? The 2003 edition of GCP has more than 9,000 words, including 13 chapter, 70 articles and 2 appendices.

2065438+In July 2008, the State Administration of Pharmaceutical Products (NMPA) issued the latest "Quality Management Standard for Drug Clinical Trials" (revised draft for comments). The new version of GCP is formulated with reference to ICH-GCP, which clarifies the responsibilities of all parties in the trial, with higher requirements, strong operability and many highlights.

Compared with the current GCP, the draft for comment has been greatly adjusted and supplemented in terms of overall framework and chapter content. The number of words has increased from more than 9,000 words to more than 29,000 words, and the chapters have been adjusted from the original 13 chapter 70 to 8 chapters 84. Five chapters, such as general principles, experimental scheme, researchers, bidders and terminology, are retained, and three chapters, such as ethics Committee, researcher manual and necessary document management, are added. Eight chapters, such as preparation and necessary conditions before clinical trials, protection of subjects' rights and interests, inspector's duties, records and reports, data management and statistical analysis, experimental drug management, quality assurance and multi-center trials, were deleted. Advance the terms and their definitions to the second chapter to facilitate readers to read and understand the contents of the specification.

From the development history of GCP, whether it is the internationally accepted ICH-GCP guiding principle or China's GCP, its update frequency is obviously accelerated and the revision period is shortened, which is in line with the trend of rapid development of the times.

China joined ICH as a full member in 20 17 and was elected as a member of the management Committee in 20 18. China's clinical trials have begun to connect with the world. For China, it is still the general idea to formulate the new regulations of GCP in China by combining the national conditions and drawing lessons from international common practices and management concepts, such as ICH related technical guidelines, FDA and EMA related regulations. China's current "Quality Management Standard for Drug Clinical Trials" was implemented in 2003, and it has been nearly 17 years. It is expected that the new regulations in China will be implemented as soon as possible.

1.ICH guide/efficiency guide

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