Advisory document for good laboratory practice:The application of the principles of GLP to in vitro studies
Some standard content:
ICS 03. 120. 20
National Standard of the People's Republic of China
GB/T 22273—2008
Advisory document for Good Laboratory Practice(GLP) :The application of theprinciples of GLP to in vitro studiesIssued on August 4, 2008
General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of ChinaAdministration of Standardization of the People's Republic of China
Implementation on April 1, 2009
GB/T 22273—2008
This standard is equivalent to the Organization for Economic Co-operation and Development (OECD) Good Laboratory Practice (GLP) Principles and Conformity Monitoring Series Document No. 14: "GLP Principles for Use in In Vitro Studies" [OECD DENV/IM/MONO(2004)26, English version]. The following editorial changes have been made to this standard:
The background introduction and introduction of OECD have been deleted. This standard was proposed and coordinated by the National Technical Committee for Standardization of Hazardous Chemicals Management (SAC/TC251). Drafting units of this standard: China Institute of Inspection and Quarantine, China Petroleum and Chemical Industry Association: Drafters of this standard: Chen Huiming, Yu Wenlian, Wang Xiaobing, Mei Jian, Sun Xin. 1 Preface
Good Laboratory Practice Recommendation Document Application of Good Laboratory Practice Principles in In Vitro Studies
GB/T22273—2008
In vitro test research systems have long been used to obtain chemical safety data related to human health and the environment. The laws of many countries require that studies on human health and the environment should be conducted in accordance with the requirements of Good Laboratory Practice (GLP). In vitro methods have traditionally been used mainly for genotoxicity testing, and risk assessment is mainly based on data obtained from in vitro test studies. Given the current emphasis on reducing the use of animals in safety testing, the role of in vitro methods has become increasingly prominent and has become a substitute or supplement for in vivo safety testing. In addition, with the development of differential toxicogenomics, toxicoproteomics, toxicometabolomics and other high-throughput screening technologies such as microarrays, the importance of in vitro safety studies is increasing.
GLP principles do not differ from other types of studies in terms of planning, management, recording, reporting and archiving requirements for safety studies. Therefore, GLP principles describe the requirements for all nonclinical health and environmental safety studies, including in vitro studies, and provide guidelines for conducting these studies. In order to promote the application of GLP principles in in vitro studies, further explanation and guidance are necessary. 2 Purpose
The purpose of this standard is to promote the correct application and interpretation of GLP principles in the organization and management of in vitro studies; at the same time, it provides guidance for testing institutions (including management, quality assurance, project sponsors and researchers) and national GLP compliance supervision departments on the correct use of GLP principles in in vitro studies.
This standard aims to provide guidance on the use and guidance of GLP principles in in vitro studies for the purpose of regulatory registration. This standard is organized in the order of different parts of GLP principles for easy reference and use. 3 Scope
This standard is the application of GLP principles to in vitro studies of nonclinical safety tests. These nonclinical safety test samples include: pharmaceuticals, pesticides, cosmetics, veterinary drugs, as well as food additives, feed additives and industrial chemicals. Test samples are usually synthetic chemicals, but there are also substances of natural or biological origin, and sometimes living organisms. The purpose of conducting these tests is to obtain the characteristics of the test substances and (or) safety data for human health and the environment. Unless exempted by law, GLP principles apply to all nonclinical health and environmental safety studies required by regulations, including: registration or licensing of pharmaceuticals, pesticides, food additives and feed additives, cosmetics, veterinary drugs and similar products, and industrial chemical management. 4 Normative references
The provisions of the following documents become the provisions of this standard through reference in this standard. For dated references, their subsequent amendments (excluding typos) or revisions are not applicable to this standard, however, parties to agreements based on this standard are encouraged to investigate whether the latest versions of these documents can be used. For undated references, the latest versions apply to this standard. GB/T 22275.3·2008 Good Laboratory Practice Implementation Requirements Part 3: Compliance of Laboratory Suppliers with Good Laboratory Practice Principles
GB/T 22275.5—2008 Good Laboratory Practice Implementation Requirements Part 5: Application of Good Laboratory Practice Principles to Short-Term Studies
GB/T 22278—2008 Good Laboratory Practice Principles 1
GB/T 22273--2008
5 Terms and DefinitionsWww.bzxZ.net
The following terms and definitions apply to this standard. 5.1
In vitro studies
Studies using microorganisms or components or simulants isolated from intact organisms, rather than intact multicellular organisms, as the test system
Under the principles of GLP, many in vitro studies are defined as short-term studies. For these in vitro studies, GB/T 22275.5-2008 should be referred to and used appropriately so that the relevant provisions can be used to facilitate the work of the project leader and quality assurance. 5,2
Reference item
In many cases, the operating guidelines for in vitro studies require the use of appropriate positive, negative and/or medium controls. According to the definition of reference materials in GB/T 22278-2008, these controls are not used to judge the reaction of the test sample in the test system, but to control the normal operation of the test system. Since the purpose of positive, negative and/or medium controls may be similar to the purpose of using reference materials, reference materials should also include "positive, negative and/or medium signatures". However, to some extent, the degree of analyzable characterization of positive, negative and/or medium reference materials should be different from the requirements for reference materials. 5.3
Aseptic conditions
Working environment conditions with minimal contamination by potential bacteria and/or pathogens. 5.4
Cell lines
Cells that have been genetically altered to become immortal. In theory, they can proliferate in vitro for a long time and, after proliferation, can be frozen and stored as cell banks. Compared with cell lines whose primary cells are different populations, immortalized cell lines are usually more uniform, more stable, and have stronger proliferative capacity. 5.5
Negative controlcontrol,negative
An independent part of the test system in which the test substance does not react; the negative control provides evidence that the test system does not react under the test conditions.
Positive controlcontrol,positive
An independent part of the test system in which the test substance reacts. The positive control provides evidence that the test system reacts under the test conditions.
Blank controlcontrol,untreated
An independent part of the test system that maintains the original culture conditions. The blank control test provides baseline data for the test system. 5.8
Conditional controlconlrol,vehiele
An independent part of the test system to which medium is added. Medium control provides evidence that the selected medium has no effect on the test system under the actual test conditions.
Criticalphases
A single process or a defined series of activities in a study on which the quality, validity, and reliability of the study depend primarily. 5.10
Cross-contamination
Due to inadvertent contamination of a test sample by another test sample, or contamination of a test system by another test sample or another test system, resulting in contamination of the test sample or destruction of the test system. 5.11
Cryopreservation
The preservation of cells and tissues under frozen conditions to maintain their vitality. 5.12
cryovial
GB/T22273—2008
Specialized bottle for cryovial storage. Cryovials should meet special requirements, i.e., they should be firmly sealed even when encountering extremely low temperatures and extreme temperature changes during freezing and thawing.
ex vivo
Cells, tissues or organs obtained from intact animals for further analysis. 5.14
gene transfection
Introduction of exogenous, complementary DNA (single or multiple genes) into host cells. 5.15
high-throughput screening uses miniaturized, robotic technology to screen single target genes, proteins, cells, tissues or compounds from huge libraries for further development based on specific activities. 5.16
Micro-arrays
Sets of microscopic chemical reaction areas are arranged in an orderly manner and spotted on a solid matrix such as a microscope slide. DNA microarrays provide a method for matching known and technically known DNA samples based on base pairing rules. DNA microarrays automate the process of identifying unknown DNA samples and detect biological samples: determine gene expression, marker patterns or nucleotide sequences of DNA/RNA. 5.17
Primary cells
primary cells
Cells newly isolated from animals or plants. Newly isolated primary cells may rapidly reverse differentiation in culture and usually have a limited lifespan. Primary cells isolated from animals or humans may represent different populations, for example, due to different purification techniques used, there are differences in cell types and differentiation states. Each isolation will be unique and cannot be strictly replicated. Primary cell culture generally requires complex nutrient media and needs to be supplemented with serum and other components. Therefore, primary cell culture systems are very difficult to standardize.5.18
proprietarymaterialproprietarymaterial
Material protected by law (patent, copyright or trademark) to prevent unauthorized use. 5. 19
test kit
A ready-to-use combination of reagents that includes all the reagents needed for an assay, test or study. 5.20
tissues
A multicellular collection of differentiated cells that are an element of an organism and have a specific function. 5.21
toxicogenomics
A system that studies how the genome responds to environmental stressors and toxicants. The goal of toxicogenomics is to discover correlations between toxic responses to toxicants and changes in the genetic profile of the organism exposed to the toxicant. Toxicogenomics combines emerging genomic and bioinformatics technologies to identify and characterize the mechanisms of action of known and suspected toxicants. Today, DNA microarrays and DNA chips are the primary research tools in toxicogenomics, used to simultaneously monitor the expression levels of hundreds of genes. 5.22 Toxicometab-onomics To link target organ toxicity with NMR spectral patterns and to identify new surrogate markers of toxicity, NMR pattern recognition techniques are used to systematically detect components of biological fluids and quantitatively measure the time-dependent multi-parameter metabolic responses of living biological systems to pathophysiological stimuli or genetic modifications. Toxicoproteomics Toxicoproteomics To study how global protein expression in cells or tissues responds to environmental stressors or toxicants. The goal of toxicogenomics is to discover the correlation between the toxicological response to toxicants and the changes in the protein profile after exposure to toxicants. 5.24
Transgenic cells
transgenic cells
Cells into which one or more foreign genes are transferred that do not express or express at a low level the characteristics and functions of the parent cell. 6 Responsibilities
6.1 Facility Managers
The primary responsibilities of facility managers are routine responsibilities, which apply to both in vivo and in vitro studies. For example, facility managers are required to ensure the qualifications of personnel and the competence of test facilities and equipment that are available to conduct studies. Facility managers should be aware that in vitro studies may affect the performance of certain responsibilities. For example, facility managers should ensure that laboratory personnel are clearly aware of their responsibilities. For in vitro studies, laboratory personnel should be provided with specialized training in sterilization and handling of biohazardous materials. In vitro studies may require the use of dedicated laboratory spaces, and the experimental process should avoid contamination of the experimental system. In addition, the supply of experimental equipment should be ensured to be consistent with the requirements of the research work. Some in vitro studies may require the use of proprietary substances and reagents. According to the requirements of GB/T22275.3·-2008, the suitability of materials used in GLP compliance studies should be produced and verified using an appropriate quality system, so the adaptability of the product is the primary responsibility of manufacturers and suppliers. The responsibility of the test institution manager is to confirm whether these requirements are fully implemented by evaluating the production, operation and policies adopted by the supplier. 6.2 Project Manager
The responsibilities of the project sponsor are independent of the type of research work. The responsibilities listed in GB/T22278·-2008 also apply to in vitro studies. The project manager is the central link in the control of the research work and should be responsible for the entire research work and report. 6.2.1 The project sponsor of in vitro studies should pay special attention to the record of the qualification and identification of the test system, which is more difficult for in vitro studies. Refer to the requirements for the record of the qualification and identification of the test system used in the test system section below. For in vivo studies, these activities are quite simple. If a specific species is used, the rationale for explaining it is to record the characteristics of these organisms so that they can become a suitable model to evaluate the effect of interest. Characterizing an animal requires simply recording the following information about the animal: species, class, subclass, source of supply, number, weight range, sex, and age. 6.2.2 The following requirements may be more difficult to achieve for in vitro studies: 6.2.2.1 The determination of the appropriateness of the test system requires the project sponsor to provide detailed information to demonstrate that the test method has been validated or that the method is structurally, functionally, and/or mechanistically similar to a validated reference test method. Before using these similar new methods, the project sponsor should provide documentation that the method has the expected performance and results with appropriate reference materials. 6.2.2.2 Documenting the characteristics of the in vitro test system may be difficult. Although the project sponsor, with the assistance of the supplier, can describe certain characteristics of the test system (e.g., cell line, age/passage, origin), the project sponsor should also record the performance results required for the test system when testing appropriate reference materials including positive, negative, blank, and/or medium reference materials. Take the special example of using proprietary materials or kits in in vitro studies. The quality of proprietary materials and kits should be guaranteed by the supplier, manufacturer or patent holder; the test site manager is responsible for ensuring that the supplier meets the above quality standards. The project sponsor is responsible for ensuring that the materials or kits used meet the research requirements by reviewing the supplier's production, operation and policies, and ensuring that the kits have been fully validated and meet the requirements for use. Since the quality and reliability of the research results are directly affected by the quality and performance of the test materials or kits, the completeness and acceptability of the quality control documents provided by the supplier are particularly important, and the project leader should conduct a thorough review and rigorous evaluation. The project leader should at least be able to determine whether the quality system adopted by the manufacturer is appropriate, and should have all the necessary documents to evaluate the suitability of the test system, such as the results of the demonstration test.
6.3 Researchers
Researchers should carefully observe that when sterile conditions are required, in vitro studies should be conducted in accordance with relevant procedures to avoid contamination of the test system with pathogens. Similarly, researchers should strictly follow the operating procedures (see reference [1) to avoid cross-contamination between test systems and ensure the integrity of the study. Researchers should be aware of and strictly comply with the requirements for isolating test systems and research involving biohazardous substances. In addition, when hazardous chemicals are used in in vitro studies, appropriate precautions should be taken to minimize the hazards. 7 Quality Assurance
Quality assurance (QA) for in vitro and in vivo studies is not very different. In some cases, in vitro studies are limited to short-term research scope. In this case, GB/T22275.5-2008 applies to in vitro studies. If permitted by the competent authority, quality assurance (QA) may conduct procedure-based inspections of in vitro studies. Because GLP principles require the use of QA to inspect key stages of the study, for in vitro studies, QA should have a good grasp of the key stages (and key aspects) of the study. Guidelines for quality assurance inspections should be developed in collaboration with project sponsors, project representatives, and researchers. QA inspections cover all specific aspects of in vitro testing, so the education and training of QA personnel should also be clearly directed to enable QA personnel to have the ability to identify potential problems in specific areas of in vitro research. Specific areas of inspection may include but are not limited to the following procedures and measures: b) monitor the composition of key cell and tissue culture media in the operation of the test system (such as calf placental serum, etc.), as well as the batch numbers of other test materials that affect the test system; b) evaluate and ensure the functional and/or morphological status (and integrity) of cells, tissues and other indicator materials: monitor potential contamination caused by foreign cells, mycoplasma, other pathogens or other accidental harmful substances; clean and disinfect facilities and equipment to minimize contamination of test samples and test systems; d) ensure that specialized equipment is used and maintained reasonably; e) ensure that cells and tissues are correctly frozen and resuscitated; ii) ensure that appropriate conditions and environment are maintained for discarded cold storage materials; ensure aseptic disinfection of materials and supplies used for cell and tissue culture; h) i) maintain appropriate isolation for different research and test systems. B Facilities
8.1 General
GLP principles dictate that test facilities should be adequate for the study and maintain a sufficient degree of separation between different study activities to ensure that each study can be conducted appropriately and without interference. In vitro studies generally occupy limited workspace and often use specialized equipment that does not preclude the running of other studies, so measures should be taken to ensure appropriate separation of in vitro studies that coexist in the same physical environment. 8.2 Test System Facilities
GLP principles require that there be a sufficient number of rooms or spaces to ensure the separation of different test systems, and that these spaces should ensure that the probability of contamination of the test systems is minimized, but the term "space" is not specifically defined and interpreted, so it is applicable to a variety of different in vitro study situations. It is important that the integrity of each test system and study is not compromised by potential contamination, cross-contamination, or mixed contamination.
8.2.1 As long as there is an adequate degree of isolation (such as proper identification, labeling or placement to distinguish between studies, etc.), cells or tissues from different projects can be cultured in the same incubator. Few test substances can volatilize and contaminate other cells or tissues in the same incubator.
8.2.2 Isolation of critical research stages is possible not only in space, but also in time. Cell and tissue culture, such as subculture GB/T 22273—2008
, addition of test substances, etc., are usually carried out in vertical laminar flow hoods to ensure a sterile environment and protect the test system, researchers and the environment. In this case, sufficient isolation is achieved by orderly handling of the test systems used in a single study to avoid cross-contamination between different studies. These operations include careful cleaning and decontamination/disinfection of the fume hood and related laboratory facilities between experiments.
8.2.3 Another important aspect is to provide a dedicated place or space with special equipment for long-term storage of test systems. Special facilities, including storage containers, should provide adequate conditions to maintain the long-term integrity of the test system. 8.3 Facilities for handling test materials and reference materials GLP principles for handling test materials and reference materials also apply to in vitro studies, and cross-contamination of test materials and reference materials is also an aspect that needs to be considered. In addition, aseptic operation should be an important consideration for in vitro studies, so the sterility of the place or space where test materials and reference materials are prepared and mixed should be ensured to protect the test system and the study to minimize the probability of contamination during the preparation of test materials and reference materials.
9 Instruments, materials and reagents
The general requirements of GLP principles for instruments also apply to instruments for in vitro studies. However, there are some specific points and specific issues that need to be explained, such as ensuring the performance and good condition of experimental equipment is important for the integrity and reliability of certain in vitro studies, such as microbalances, micropipettes, laminar flow hoods or incubators should be regularly maintained and monitored and calibrated when in use. For special instruments, key parameters need to be determined and continuously monitored, or reading ranges should be set and alarm devices should be equipped. The requirements for labeling and expiration dates of reagents in GLP principles also apply to in vitro studies. 10 Test Systems
In vitro test systems are primarily biological systems, although alternatives to conventional in vivo tests have been developed recently (e.g., gene arrays for toxicogenomics) that also exhibit some of the attributes of physico-chemical test systems, and others, such as toxicometabolomics, may be primarily analytical. Kits (including proprietary kits) should be considered test systems. 10.1 Test System Conditions
As with any biological test system, appropriate conditions should be determined, maintained, and monitored during storage and study to maintain the quality and integrity of the test system. This includes documentation, maintenance, and monitoring of test system stability and response, including recording of cell passage numbers and cell population doublings. Environmental conditions should also be recorded (e.g., concentration of liquid nitrogen in liquid nitrogen cryopreservation systems, temperature, humidity, and CO2 in incubators), as well as actions that maintain the quality and integrity of the test system (e.g., use of antibiotics or sterilization, subculturing, selection of volatile cultures to reduce the frequency of natural events). Because the maintenance of appropriate environmental conditions during storage of test systems can have a greater impact on data quality than other biological systems, it is particularly important to maintain the quality and reliability of recorded data. 10.2 Newly Accepted Test Systems
Detailed information provided by the supplier for the in vitro test system (e.g., source, age/passage number, number of cell doublings, and other relevant characteristics that can help identify the test system) should be checked and retained in the study records. The test system should be evaluated for stability, suitability (e.g., cell and tissue function and/or morphology, known or suspected microbial or viral contaminants of the test) and reactivity against predetermined criteria. The results of these evaluations should be recorded and retained in the study records. If no evaluation is possible, such as primary cell cultures or "reconstructed organs", there should be a mechanism between the supplier and the user to determine and record the suitability of the test system. Determination and recording of responses to negative and positive controls will provide sufficient evidence of the reactivity of a particular test system. Any problems with the test system that may affect the quality, accuracy, and reliability of the study should be recorded and discussed in the final report. If there are problems with the test system supplied by the supplier, they should be communicated to the supplier and corrective actions should be taken.
10.3 Test system records
10.3.1GLP principles require that the source, arrival date and status of the test system upon arrival should be fully recorded. For cells and tissues, the records should include not only the direct source (such as the supplier) but also the primary source of the cells or tissues (such as primary cells or tissues with donor properties, cell lines established from a precise source, etc.). Other information should include but is not limited to the method of initially obtaining the cells or tissues6
GB/T22273—2008
(such as biopsies of normal or cancerous tissues from tissue explants, gene transfer by plasmid transfection or viral transduction, etc.), the years of transportation and storage, the number of cell line generations, culture conditions and subculture intervals, freezing/thawing conditions, etc. In addition, for transgenic test systems, the traits of the transgene need to be determined and their expression levels monitored under appropriate conditions. 10.3.2 During storage and use, special attention should be paid to the correct labeling of the test system and regulations should be adopted to ensure the durability of the label. In particular, key labeling factors such as container size and storage conditions (such as quick freezing, multiple test systems stored in one liquid nitrogen container) should be addressed. Measures should be taken to ensure that the test system can be correctly identified at all times. 10.3.3 The GLP principles for test substances and reagents on labeling and expiration dates also apply to test kits used in in vitro test systems. Whether the test kit is used for a test system or for other purposes such as analysis, it should have a clear expiration date. The expiration date can only be extended with a written evaluation (and analysis). For test kits used in test systems, the evaluation records should include: historical records and evidence of the testing of multiple batches of test kits on positive, negative and (or) medium references, and even if the test results do not deviate from the historical control values after the expiration date, the project manager should provide evidence of the evaluation process if he or she decides to extend the expiration date. 10.3.4 To avoid confusion, the terminology of the test system should be clearly defined, and the labeling of the test system and all records from individual studies should bear the formally recognized name of the test system. 10.4 Test substances and reference materials (including negative and negative controls) 10.4.1 In addition to the provisions of the GL.P principles, there are generally no special requirements for the receipt, handling, sampling, storage and identification of test substances and reference materials used in in vitro test systems. However, strict aseptic operating conditions are required during sample handling to avoid microbial contamination of the test system.
10.4.2 For negative, medium and positive controls, if evidence can be provided that they will produce the expected normal results in the test system. It may or may not be necessary to determine their concentration and homogeneity. 10.4.3 The validity period of controls may be extended by evaluation and analysis of the recorded data. This evaluation consists of documentary evidence that the responses of negative, medium and positive controls in each test system do not deviate from the historical control values recorded for the test equipment and are comparable to the reference values in the literature.
10.5 Standard Operating Procedures (SOPs)
In addition to 3.7.4.1 to 3.7.4.5 of GB/T22278-2008, some specific steps and processes for in vitro tests should be described in the standard operating procedures. Therefore, SOPs should have additional requirements, not limited to the following test facility activities related to in vitro tests. 10.5.1 Facilities
Environmental monitoring, cleaning and disinfection of pathogens in the air and laboratory bench surfaces, and related measures to be taken for contaminated test equipment or space.
10.5.2 Instruments
Use, maintenance, real-time monitoring, cleaning and disinfection of cell and tissue culture instruments and equipment (such as laminar flow hoods and incubators); liquid nitrogen level monitors for storage boxes; calibration and monitoring of temperature, humidity and CO2 concentration of incubators. 10.5.3 Materials, reagents and solutions
Evaluation of their suitability, extension of shelf life, evaluation and maintenance of sterility, screening of common pathogens, procedures for media selection and use, and procedures for testing the compatibility of media with test systems. 10.5.4 Test systems
Storage conditions and freezing and thawing procedures for cells and tissues, tests for common pathogens, visual inspection for contamination; validation procedures for test systems upon arrival and during use (whether upon arrival or in subsequent storage), with corresponding qualification indicators to ensure that their performance and status meet the requirements, morphological evaluation, control of phenotypic or chromosome stability, control of transgenic stability; culture initiation mode, culture conditions, and passage intervals, handling of biohazardous materials and test systems, and handling procedures for test systems. 10.5.5 Implementation of the study
Sterilization technology, standards for determining study validity, and standards for repeated measurements. 10.5.6 Quality assurance
Definition of key stages of the test. Inspection frequency. 7
GB/T22273—2008
10.6 Conduct of studies and reporting of study results10.6.1 The requirements of GLP principles for the conduct of in vitro studies are the same as those for regulated safety studies. In many cases, in vitro studies should be conducted in a manner consistent with GLP principles, and GB/T22275.5—2008 and GB/T22278-2008 should be combined for reference. 10.6.2 In in vitro studies, there are a number of special issues that need to be addressed in the study plan and the final study report. These issues are mainly scientific and technical issues, such as the requirement that internal standards [appropriate positive, negative, blank and/or medium controls] should be set up to control bias and evaluate the operation of the test system. The relevant OECD test guidelines or other relevant references can be used to address which issues should be addressed in the study plan and final report. 10.7 Storage and Preservation of Records and Materials
10.7.1 The general requirements for storage and preservation of records and test materials in the GLP principles also apply to in vitro studies. In addition, in vitro studies should consider samples of test systems that can be stored for a long time, especially the preservation of very limited or difficult to obtain test systems (such as special subclones of cell lines, genetically modified cells, etc.) so that the characteristics and/or reproducibility of the test system can be confirmed. 10.7.2 For in vitro studies that can be classified as short-term studies, especially when safety studies are mainly conducted in vitro, consideration should be given to the preservation of test samples.
10.7.3 Historical records of positive, negative, blank and/or medium control results used to establish the acceptable reaction range of the test system should be preserved.
Art Examination Literature
GB/T22273—2008
Good Cell Culture Practice.http://ccvam.jrc.it/puhlication/index5007.html.MIAME Guidelines.http://mnged.org/Warkgroups/MIAME/miamc.html.ECVAM.http://ecvam.jrc.it/index.htm.ICCVAMhttp://iccvam.niehs.nih.gov/.9
GB/T 22273-2008
National Standard of the People's Republic of China
Good Laboratory Practice Recommendation Document
Good Laboratory
Application of Standard Principles in In Vitro Studies
GB/T 22273-—2008
Published and distributed by China Standards Press
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website: spc.niet,cn
Tel: 6852394668517548
Printed by Qinhuangdao Printing Factory of China Standards Press Distributed by Xinhua Bookstores in various regions
Format: 880×12301/16 Printing sheet: 1 Word count: 17,000 words First printing in October 2008
First edition in October 2008
Book number: 155066·1-33860 Price: RMB 16.00 Any printing or binding error will be replaced by our publishing center Copyright infringement will be investigated
Report telephone: (010) 685335334 Test system
Storage conditions and freezing and thawing procedures for cells and tissues, tests for common pathogens, visual inspection for contamination; validation procedures for test systems upon arrival and during use (both upon arrival and in subsequent storage), with corresponding qualification indicators to ensure that their performance and status meet the requirements, morphological evaluation, control of phenotypic or chromosome stability, control of transgenic stability; culture initiation mode, culture conditions and passage intervals, handling of biohazardous materials and test systems, and handling procedures for test systems. 10.5.5 Implementation of the study
Sterilization technology, standards for determining study validity, standards for repeated measurements. 10.5.6 Quality assurance
Definition of key stages of the study. Inspection frequency. 7
GB/T22273—2008
10.6 Implementation of the study and reporting of study results 10.6.1 The requirements of GLP principles for the implementation of in vitro studies are the same as those for regulated safety studies. In many cases, in vitro studies should be conducted in a manner consistent with GLP principles, and GB/T 22275.5-2008 and GB/T 22278-2008 should be combined for reference. 10.6.2 In in vitro studies, there are a series of special issues that need to be clearly addressed in the study plan and the final study report. These issues are mainly scientific and technical issues, such as the requirement that internal standards [appropriate positive, negative, blank and (or) medium controls should be conducted simultaneously with the test substances] set to control deviations and evaluate the operation of the test system. What issues should be addressed in the study plan and final report can refer to the relevant OECD test guidelines or other relevant references. 10.7 Storage and preservation of records and materials
10.7.1 The general requirements for the storage and preservation of records and test materials in the GLP principles also apply to in vitro studies. In addition, in vitro studies should consider the long-term storage of test system samples, especially the storage of very limited or difficult to obtain test systems (such as special subclones of cell lines, transgenic cells, etc.) so that the characteristics and/or reproduction of the test system can be confirmed. 10.7.2 For in vitro studies that can be classified as short-term studies, especially when safety studies are mainly conducted in vitro, the storage of test samples should be considered.
10.7.3 Historical records of positive, negative, blank and/or medium control results used to establish the acceptable reaction range of the test system should be retained.
Art Examination Literature
GB/T22273—2008
Good Cell Culture Practice.http://ccvam.jrc.it/puhlication/index5007.html.MIAME Guidelines.http://mnged.org/Warkgroups/MIAME/miamc.html.ECVAM.http://ecvam.jrc.it/index.htm.ICCVAMhttp://iccvam.niehs.nih.gov/.9
GB/T 22273-2008
National Standard of the People's Republic of China
Good Laboratory Practice Recommendation Document
Good Laboratory
Application of Standard Principles in In Vitro Studies
GB/T 22273-—2008
Published and distributed by China Standards Press
No. 16, Sanlihebei Street, Fuxingmenwai, Beijing
Postal code: 100045
Website: spc.niet,cn
Tel: 6852394668517548
Printed by Qinhuangdao Printing Factory of China Standards Press Distributed by Xinhua Bookstores in various regions
Format: 880×12301/16 Printing sheet: 1 Word count: 17,000 words First printing in October 2008
First edition in October 2008
Book number: 155066·1-33860 Price: RMB 16.00 Any printing or binding error will be replaced by our publishing center Copyright infringement will be investigated
Report telephone: (010) 685335334 Test system
Storage conditions and freezing and thawing procedures for cells and tissues, tests for common pathogens, visual inspection for contamination; validation procedures for test systems upon arrival and during use (both upon arrival and in subsequent storage), with corresponding qualification indicators to ensure that their performance and status meet the requirements, morphological evaluation, control of phenotypic or chromosome stability, control of transgenic stability; culture initiation mode, culture conditions and passage intervals, handling of biohazardous materials and test systems, and handling procedures for test systems. 10.5.5 Implementation of the study
Sterilization technology, standards for determining study validity, standards for repeated measurements. 10.5.6 Quality assurance
Definition of key stages of the study. Inspection frequency. 7
GB/T22273—2008
10.6 Implementation of the study and reporting of study results 10.6.1 The requirements of GLP principles for the implementation of in vitro studies are the same as those for regulated safety studies. In many cases, in vitro studies should be conducted in a manner consistent with GLP principles, and GB/T 22275.5-2008 and GB/T 22278-2008 should be combined for reference. 10.6.2 In in vitro studies, there are a series of special issues that need to be clearly addressed in the study plan and the final study report. These issues are mainly scientific and technical issues, such as the requirement that internal standards [appropriate positive, negative, blank and (or) medium controls should be conducted simultaneously with the test substances] set to control deviations and evaluate the operation of the test system. What issues should be addressed in the study plan and final report can refer to the relevant OECD test guidelines or other relevant references. 10.7 Storage and preservation of records and materials
10.7.1 The general requirements for the storage and preservation of records and test materials in the GLP principles also apply to in vitro studies. In addition, in vitro studies should consider the long-term storage of test system samples, especially the storage of very limited or difficult to obtain test systems (such as special subclones of cell lines, transgenic cells, etc.) so that the characteristics and/or reproduction of the test system can be confirmed. 10.7.2 For in vitro studies that can be classified as short-term studies, especially when safety studies are mainly conducted in vitro, the storage of test samples should be considered.
10.7.3 Historical records of positive, negative, blank and/or medium control results used to establish the acceptable reaction range of the test system should be retained.
Art Examination Literature
GB/T22273—2008
Good Cell Culture Practice.http://ccvam.jrc.it/puhlication/index5007.html.MIAME Guidelines.http://mnged.org/Warkgroups/MIAME/miamc.html.ECVAM.http://ecvam.jrc.it/index.htm.ICCVAMhttp://iccvam.niehs.nih.gov/.9
GB/T 22273-2008
National Standard of the People's Republic of China
Good Laboratory Practice Recommendation Document
Good Laboratory
Application of Standard Principles in In Vitro Studies
GB/T 22273-—2008
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