GLP, the abbreviation of Good Laboratory Practice, is a dedicated quality management system for improving experimental data quality and guaranteeing validity and authenticity of experimental results, including the planning, implementation, supervision, and record filing of experimental research. To all aspects that can affect experimental results and interpretation of results. In China, laboratory management practices target mainly at safety evaluation experiments required by enrollment and registration of drugs, pesticides, and industrial chemicals.
The main purposes of GLP are to put all links of tests under strict control, that is, control strictly a variety of subjective and objective factors that may affect the accuracy of experimental results so as to reduce experimental errors and ensure the authenticity of experimental results.
I. The origin of GLP
GLP was adopted for the first time as legislation in New Zealand in 1972 and Organization for Economic Cooperation and Development (OECD in short) formulated the GLP principles in 1981. GLP specifications have also been implemented successively in Japan, South Korea, Switzerland, Sweden, Germany, Canada, the Netherlands and other countries in the mid-80s. Up to now GLP specifications have become a laboratory quality management system widely recognized by countries all over the world.
II. Development of GLP in China
Relatively speaking, GLP gets started late in China but develops rapidly. On October 14, 1999, the former National Medical Products Administration issued Drug Non-clinical Research Quality Management Practice (Trial), which clarifies setting and responsibilities of personnel at all levels of test agencies, responsibilities of quality assurance units, experimental facilities, SOP, and implementation requirements of specific research task of drug non-clinical research. GLP specification was formally implemented after two revisions in 2003 and 2007. According to regulations of the former National Medical Products Administration, from Jan. 1, 2007 on, safety evaluation studies of all new drugs must be carried out in a GLP certified laboratory.
The idea of GLP has also gradually expanded to the safety evaluation system of other toxic and harmful substances (Such as pesticides, new chemical substances, etc.). Some ministries like the former MOA of the PRC and the former SEPA have also successively formulated their GLP system documents.
When it comes to safety assessment of new chemical substances, to regulate related test reports required by notification of new chemical substances, the former State Environmental Protection Administration released and implemented in 2004 The Guidelines of Chemical Testing Good Laboratory Practices, which regulated the laboratory quality management of chemical tests. Over the past dozen years, GLP labs regarding chemical ecology and toxicology tests flourished. From April 1, 2017 on, the former MEP canceled GLP compliance certification of the ecotoxicology laboratories. A supervision method of self-declaration by experimental organizations and regular check and reviews by competent authority was adopted instead. The Ministry of Health promulgated in 2001 Chemical Toxicity Appraisal Management Regulations and Chemical Toxicity Appraisal Agency Qualification Certification Work Procedures and the like, which were not GLP specifications, but put forward normative requirements on chemical toxicity identification agencies and identification of chemical toxicities.
When it comes to safety evaluation of pesticides, pesticide GLP certification began in China in 2002. Institute for the Control of Agrochemicals, MOA and Shenyang Research Institute of Chemical Industry shared the sub-project "Establishment and improvement of GLP/SOP system for pesticide safety evaluation" of "New Pesticide Creation Research and Industrialization Key Technology Development" under the "Tenth Five-Year Plan" National Major Science and Technology Project from 2002 to 2003. Good Laboratory Practice for Pesticide Toxicology Safety Evaluation was formulated as a result of the implementation of the project. Great progress was made with GLP in the pesticide industry in the dozen years thereafter.
On the whole, regulatory agencies for different products have established their GLP systems respectively.
III. GLP certification in China
1. GLP certification of National Medical Products Administration
National Medical Products Administration inspects the organization and management system, personnel, experimental facilities, equipment, operation and management of experimental projects of drug non-clinical research institutions engaged in safety evaluation and assesses their compliance with GLP. GLP certification comprises three major links: application and acceptance, data review and scene investigation, and review and publicity. The review is based upon Drug Non-clinical Research Quality Management Standard Certification Standards.
Scope of review: 6 key items, 30 key items and 244 general items.
The inspection team will appraise problems inconsistent with GLP requirements discovered during on-site inspection and draw a conclusion. National Medical Products Administration will, after analysis and summary, make a decision: approve, not to approve or need rectification.
By April 2020, more than 100 research institutions engaged in safety evaluation have passed GLP certification of the National Medical Products Administration, and many experimental institutions are now in preparation for their certification applications.
2. GLP certification of China National Accreditation Service for Conformity Assessment (CNAS)
To enhance chemical safety management level of China, CNAS has established Chinese GLP in accordance with international accepted principles and GLP pilot evaluation has started from Mar. 2008. GLP evaluation procedures were revised in Feb. 2013, the technical review of which, as organized by CNAS, was conducted by China National Accreditation Service for Conformity Assessment.
Review Basis: Good Laboratory Practice (GLP) Principles, Good Laboratory Practice (GLP) Compliance Evaluation Procedure, OECD GLP Guidelines, GB/T 22275 Requirements of Conduct for Good Laboratory Practice(GLP) and the like.
Evaluation Fields: physicochemical properties test, toxicological studies, mutagenic studies, environmental toxicity studies of aquatic and terrestrial organisms, environmental toxicity studies of aquatic and terrestrial organisms, behavioral studies in water, soil and air, bioconcentration studies, residue studies, studies of impact on simulated and natural ecosystems, and analytical chemistry and clinical chemistry tests.
At present, 20 domestic laboratories have passed CNAS GLP review.
3. GLP certification of MARA
It refers mainly to GLP qualification accreditation of test units engaged in pesticide registration.
Review Basis: Regulation on Pesticide Administration, Measures for the Administration of the Pesticide Registration, Measures for the Administration of the Pesticide Registration Experiment, Pesticide Registration Test Quality Management Practice, and Regulations for the Review of Pesticide Registration Test Units. Up to now, 173 laboratories in China have passed GLP review of MARA.
4. GLP compliance self-declaration of MEE
From April 1, 2017, the former MEP canceled GLP review and announcement system for chemicals test agencies and requested them to publish GLP compliance self-declaration on the official websites and website of MEESCC. Review and subsequent supervision and management of test data are strengthened through social supervision, routine inspection, flight inspection, causal inspection and sampling verification. As of the end of April 2020, a total of 18 test agencies have been included in the GLP compliance self-declaration list.
Table 1 below show competent departments of GLP certification and fields involved in China.
Table 1 Details of GLP certification and competent departments in China
GLP certification and competent department
National Medical Products Administration
Drug and non-clinical safety evaluation
More than 100 institutions have passed certification
China National Accreditation Service for Conformity Assessment (CNAS)
20 institutions have passed certification
Pesticides, veterinary drugs, and feed additives
173 agencies have passed qualification accreditation
New chemical substances, and industrial chemicals
18 institutions have finished self GLP compliance declaration and been recorded on MEESCC website
Statistics above are as of April 29, 2020.
IV. Mutual recognition between China GLP and international GLP
There are great differences in the implementation of GLP at home and abroad, which are mainly reflected in the following aspects according to the comparison of implementation time, scope, management department and certification standards of GLP: Most of the domestic agencies implementing GLP stay at the government-led stage, that is, the government agencies and research institutes undertake research tasks, and GLP companies develop slowly, while enterprises are the main force for developing GLP abroad; Drug GLP is relatively mature in China. In the process of gradual development, GLP specifications in other fields have been widely implemented in European and American countries, and most of them are approaching perfection; Most certifications domestically are institutional ones, while Europe and the United States are dominated by project certifications, by which GLP agencies get prepared for projects first, which will then be reviewed by the certification bodies then; GLP management department in our country is too scattered, with a department responsible for a specific fields, while relatively concentrated management is practiced in the United States.
Existing Chinese GLP system is implemented and supervised by four different authorities apiece. Drug GLP is under the control of National Medical Products Administration of State Administration for Market Regulation, GLP for new chemical substances and industrial chemicals is under the control of MEE, GLP for pesticides and veterinary drugs is under the control of MARA and GLP for chemicals is under the control of CNAS.
Mutual acceptance of chemicals safety assessment data (MAD) is a multilateral agreement based on OECD MAD, which establishes a test data sharing mechanism, reducing unnecessary repeated tests. Under this system, chemicals safety assessment data completed by an OECD member or non-member state joining MAD in accordance with OECD test guidelines and OECD GLP specification must be accepted by all member states and non-members that have joined MAD. However, due to a variety of complicated reasons, China is not yet a member of OECD and joined only one of its committee in the capacity of an observer. As such, China has not realized GLP MAD with OECD yet. In 2003 a Chinese laboratory passed the Dutch certification for the first time, and obtained GLP qualification in compliance with OECD guidelines. Up to now, 23 laboratories have successively obtained GLP certification from OECD member countries. The main certification countries are the Netherlands, Belgium, Germany, and Poland. It means that a GLP report meeting the requirements of certification countries can be issued in the designated technical field.
In summary, GLP system of China grew out of nothing and has achieved great development in the last 30 years. State Administration for Market Regulation, MEE, MARA and CNAS all have carried out GLP audit and certification. A total of more than 300 test agencies have passed China GLP certification and the amount of GLP conformity test agencies certified by OECD member states has reached 23. Scattered as GLP management departments are, development of Chinese GLP test agencies is limited to some extent.