Guidance for GLP monitoring authorities - Part 2: Guidance for the conduct of laboratory inspections and study audits
Some standard content:
ICS 03. 120. 20
National Standard of the People's Republic of China
GB/T 22274.2—2008
Guidance for Good Laboratory Practice (GLP) monitoring authorities-Part 2: Guidance for the conduct of laboratoryinspections and study audits audits2008-08-04 Issued
General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China Standardization Administration of China
Reserve you
2009-04-01 Implementation
GB/T22274 "Guidelines for Good Laboratory Practice Supervision Departments" consists of three parts: - Part 1: Guidelines for Good Laboratory Practice Conformity Supervision Procedures; - Part 2: Guidelines for Performing Laboratory Inspections and Research Audits; - Part 3: Guidelines for the Preparation of Good Laboratory Practice Inspection Reports. This part is Part 2 of GB/T22274. GB/T22274.2—2008
This part is equivalent to the Organization for Economic Cooperation and Development (OECD) Good Laboratory Practice (GLF) Principles and Conformity Supervision Series Document No. 3: Guidelines for Good Laboratory Practice Supervision Departments: Revised Guidelines for Performing Laboratory Inspections and Research Audits [OCDE/GD(95)67]. The following editorial changes have been made to this part: (1) Foreword and Introduction in the original text have been deleted; (2) Part II: OECD Council Directives related to GLP principles and compliance supervision.
This part was proposed and coordinated by the National Technical Committee for Standardization of Hazardous Chemicals Management (SAC/TC251). The drafting unit of this part: Shandong Exit-Entry Inspection and Quarantine Bureau. The main drafters of this part: You Ruihua, Tao Qiang, Wan Min, He Fei, Jiang Shiming. 1 Scope
Guidelines for Good Laboratory Practice Supervision Departments
Part 2: Guidelines for Performing Laboratory Inspections
and Study Audits
GB/T 22274.2—2008
This part of GB/T 22274 specifies the GLP supervision departments' test facility inspections, inspection procedures, study audits, and the completion of inspections or study audits.
This part applies to GLP supervision departments established in my country. 2 Normative references
The clauses in the following documents become clauses of this part through reference in this part of GB/T 22274. For dated references, all subsequent amendments (excluding errata) or revisions do not apply to this part, however, parties to agreements based on this part are encouraged to investigate whether the latest versions of these documents can be used. For undated references, the latest versions apply to this part. GB/T 22274.1 Guidelines for Good Laboratory Practice Supervision Departments Part 1: Guidelines for Good Laboratory Practice Compliance Supervision Program GB/T 22278 Principles of Good Laboratory Practice
3 Terms and definitions
The terms and definitions in GB/T 22278 and GB/T 22274.1 apply to this part. 4 Inspection of testing institutions
4.1 For regulatory purposes, any testing institution that produces health or environmental safety data may be inspected for compliance with GLP principles. Inspectors may be required to review data related to the physical, chemical, toxic or ecotoxic properties of substances or preparations. In some cases, the inspector may need the assistance of subject matter experts. 4.2 The wide variety of facilities (related to physical layout and management structure) and types of studies that the inspector will encounter means that the inspector should rely on his or her own judgment to assess the degree and extent of compliance with the principles of GLP. Nevertheless, the inspector should strive to maintain a consistent approach when evaluating whether a particular facility or study complies with the principles of GLP. 4.3 In the following sections of this section, guidance is provided on various aspects of the facility, including the personnel and procedures that are likely to be investigated by the inspector; and in each section there is a statement of purpose and a list of specific items that may be considered during the facility inspection. These lists are not intended to be all-inclusive and should not be misunderstood. 4.4 The inspector should not be concerned with the scientific soundness of the study design or the interpretation of the effects of the study results on human health or the environment. These aspects are the responsibilities of the regulatory authorities to whom all data are submitted for oversight. 4.5 Inspections of facilities and audits of studies inevitably interfere with the normal work of the facility. Therefore, the inspector should plan carefully and, if practicable, schedule visits to certain areas in accordance with the wishes of facility management. 4.6 During the inspection of a testing facility and the audit of a study, the inspector will have access to confidential, commercially valuable information. They should ensure that only authorized personnel have access to this information. The responsibilities in this regard have also been defined in the GLP Compliance Monitoring Plan. 5 Inspection Procedures
5.1 Pre-audit
5.1.1 Familiarize the inspector with the management structure, building layout, and scope of studies of the facility to be inspected. GB/T 22274.2-2D08
5.1.2 Before conducting a testing facility inspection or a study audit, the inspector should familiarize himself with the facility to be visited and review any existing information about the facility. This information may include previous inspection reports, facility layout, organizational charts, study reports, protocols, and personnel resumes (CVs). These documents will provide the following information:
a) The type, size, and layout of the facility;
b) The scope of studies that may be encountered during the inspection;) The management structure of the facility.
5.1.3 The inspector should pay special attention to deficiencies revealed by the test facility in previous inspections. If the test facility has not been inspected before, a visit can be made before the inspection to obtain relevant information. 5.1.4 The test facility can be informed of the date and time of the inspector's arrival, the purpose of the visit, and the expected duration. This will ensure that the test facility has the appropriate personnel and documents prepared. If there are special documents and records that need to be investigated, it is best to confirm with the test facility before the visit so that they can be obtained immediately during the inspection. 5.2 Initial meeting
5.2.1 On the first day: Inform the management and personnel of the organization of the reasons for the test facility inspection and study audit to be conducted, and determine the inspection area, the research projects selected for audit, the documents and personnel that may be involved. 5.2.2 At the beginning of the visit, the inspector should discuss with the organization's management the details of the management and implementation of the test facility inspection and study audit. During the initial meeting the inspector should: a) outline the scope and purpose of the visit; state the documents required for the inspection of the test facility, such as lists of ongoing and completed studies, study plans, standard operating procedures, study reports, etc. Copies of relevant documents should be agreed upon at this time, if required; b) obtain or request information on the management structure (organization) and personnel of the facility; if non-GLP studies are conducted in areas of the test facility where GLP studies are conducted, request information; c) preliminarily identify the areas of the facility to be inspected during the inspection; state the documents and samples required for the study review of the selected studies (ongoing or completed); and inform that a closing meeting will be held at the end of the inspection. g) 5.2.3 It is recommended that the inspector establish contact with the test facility's quality assurance department before conducting further inspections of the test facility. 5.2.4 As a general rule, it will be helpful for the inspector to be accompanied by a quality assurance officer during the inspection of the facility. 5.2.5 The inspector may request a room to be set aside for document inspection and other activities. 5.3 Organization and Personnel
5.3.1 Purpose: To determine whether the test organization is equipped with sufficient qualified personnel, human resources and support services to ensure the different types and quantities of research undertaken by it, whether the organizational structure is appropriate; whether the management has established personnel training and health supervision policies that are suitable for the research undertaken by the organization.
5.3.2 Management should be required to submit some information,Such as: Floor plan: Facility management and technical organization chart; Resumes of personnel involved in the study and the study being audited; List of ongoing and completed studies, which may include information such as study type, start and/or completion date, test system, method of test sample application, name of project leader, etc.; e) Personnel health supervision policy; Personnel job descriptions and personnel training plan and records; g) Organization Standard Operating Procedures (SOPs): Specific SOPs related to the study or procedure being inspected or audited; h) i) List of project leaders and clients related to the audited study. 5.3.3 The inspector should specifically check: List of ongoing and completed studies to assess the level of work of the test organization; a) Identity and qualifications of project sponsors, quality assurance department heads and other personnel; b) c) Existing SOPs for all relevant test areas. 5.4 Quality Assurance Plan
GB/T 22274.2—2008
5.4.1 Purpose: To determine whether the management mechanism adopted to ensure that the study is conducted in accordance with the principles of GLP is appropriate. 5.4.2 The head of the quality assurance department shall, as required, describe the system and methods used for quality assurance inspection and supervision of the study, as well as the system for recording observations during the quality assurance supervision process. The inspector should check: the qualifications of the quality assurance supervisor and all quality assurance personnel; a) the independence of the quality assurance department's functions from those of the researchers; b) how the quality assurance department arranges and implements inspections and monitors key stages in the study; what resources are available for quality assurance inspection and monitoring activities:
for studies of short duration that do not allow for individual monitoring, the existence of sampling monitoring arrangements; d) the breadth and depth of the quality assurance department's supervision during the implementation phase of the study; the breadth and depth of the quality assurance department's supervision during the daily operation of the experimental facility; the quality assurance procedures, which are used to check the final report to ensure that it is consistent with the original data; g) the reports that managers receive from the quality assurance department on problems that may affect the quality and integrity of the study; h) the actions taken by the quality assurance department when deviations are discovered; i) the tasks of the quality assurance department if the study or part of the study is conducted in a contract laboratory; k) the role of the quality assurance department in reviewing, revising and updating standard operating procedures. 5.5 Facilities
5.5.1 Purpose: To determine whether the size, design, location and other characteristics of the test facilities (including indoor and outdoor facilities) are appropriate and meet the needs of the research undertaken.
5.5.2 The inspector should check:
a) The design of the facilities should provide adequate isolation so that the test samples, animals, feed, pathological samples, etc. of one study will not be mixed with those of other studies;
Environmental control and monitoring procedures exist and are fully functional in important areas. For example, rooms for animal and other biological test systems, test sample storage areas and laboratory areas;
c) There is adequate daily sanitation management for various facilities, and pest control procedures can be adopted when necessary. 5.6 Management, Housing and Containment of Biological Test Systems 5.6.1 Purpose: If animals or other biological test systems are used in the research, determine whether the test organization has sufficient support facilities and conditions to ensure the management, housing and containment of the test systems, and strictly prevent the occurrence of tension and other problems that affect the test systems and thus affect the quality of the data.
5.6.2 The types of test systems used in the research conducted by a test facility may require a variety of animals, plants, and microorganisms or other cellular or subcellular systems, which will determine the content of the inspection related to management, housing and containment control. Relying on their own judgment, the inspector will check the following in relation to the test system:
a) There are sufficient test facilities for the test system and the test; b) There are arrangements for the quarantine of animals and plants introduced into the facility, and such arrangements function satisfactorily; There are arrangements for the isolation of animals (or other elements of the test system, if necessary) that are known or suspected to be sick or disease carriers,
There is adequate supervision of health, behavior or other aspects and record keeping appropriate to the test system; d)
Equipment for maintaining the environmental conditions required for each test system should be sufficient in number, well maintained and in effective working order; e)
Animal cages, racks, tanks and other containers and associated equipment should be kept sufficiently clean; f)
Environmental conditions and support systems are inspected and analyzed to ensure that they meet the requirements; g)
GB/T 22274.2—2008
h) Facilities are available to remove and dispose of animal excreta and waste from the test system to minimize pest outbreaks, odors, disease hazards, and environmental contamination;
i) Areas are provided for the storage of animal feed or similar materials for all test systems; other items such as test samples, pesticides, or disinfectants should not be stored in this area, which should be separated from animal housing areas or areas where other biological test systems are stored; i) Stored feed and bedding should be protected from deterioration due to adverse environmental conditions, pests, or contamination. 5.7 Equipment, Materials, Reagents, and Specimens
5.7.1 Purpose: To determine whether the test facility is located appropriately; whether the operating equipment is of sufficient quantity and testing capacity to meet the needs of the tests conducted in the institution; and whether materials, reagents, and specimens are properly labeled, used, and stored. 5.7.2 The inspector should check that:
the equipment is clean and in good working order;
records of operation, maintenance, inspection, calibration and validation of measuring equipment and instruments (including computerized systems) are kept; b)
raw materials and chemical reagents are correctly labeled and stored at appropriate temperatures, and the expiration date should also be noted. The labels of reagents should indicate their source, name, concentration and (or) other relevant information; samples should indicate the test system, study, nature and collection date; d)
the equipment and raw materials used should not cause any significant change in the test system. e
5.8 Test system
5.8.1 If the organization needs multiple test systems due to the research it undertakes, it should determine whether it has adequate procedures to handle and control these test systems: for example: physical and chemical systems, cell and microbial systems, plant or animal systems. 5.8.2 Physical and Chemical Systems
The inspector shall check:
a) The stability of the test samples and reference materials is determined in accordance with the requirements of the study plan and that the reference materials specified in the study plan are used: In the case of automated systems, data generated in the form of images, recorded curves or computer printouts shall be recorded as raw data and b
archived.
5.8.3 Biological Test Systems
Taking into account the above-mentioned aspects of the management, placement and containment of biological test systems, the inspector shall check: a) The test system is consistent with that specified in the study plan; b) The test system is adequately and (if necessary and appropriate) uniquely identified throughout the study; and relevant records of the receipt of the test system and the number of test systems received, used, replaced and discarded are kept; all necessary and appropriate identification information is on the culture environment or container of the test system; d) Multiple studies using different substances on the same animal (or the same biological test system) are adequately isolated; c) No Animals (or other biological test systems) of different species are adequately separated in time and space; Environmental conditions of the biological test system are consistent with the study plan or standard operating procedures, such as temperature, or light and/or dark cycle: g) Records of the test system (including receipt, handling, housing or containment control, management and health assessment) are appropriate: Written records of inspection, quarantine, morbidity, mortality, behavior, diagnosis and treatment of animal and plant test systems (or other biological test systems) are maintained; i) At the end of the study, there are specific provisions for the appropriate disposal of the test system. 5.9 Test Samples and Reference Materials 5.9.1 Date: Determine whether the test facility has established procedures in advance to a) ensure that the identification information, potency, quantity and composition of test samples and reference materials are consistent with their specifications; b) appropriately receive and store test samples and reference materials. 5.9.2 The inspector should check:
a) There are written records of the receipt (indicating the responsible person), processing, sampling, use and storage of test samples and reference materials; b) The containers of test samples and reference materials are correctly labeled; 4
c) The storage conditions are suitable for maintaining the concentration, purity and stability of test samples and reference materials; GB/T 22274.2—200B
Written records are maintained to determine the identity, purity, composition, and stability of test samples and reference materials;
Written records are maintained, if possible, to prevent contamination of test samples and reference materials;
Written records are maintained, if possible, for mixtures containing test samples and reference materials, procedures are in place to determine the homogeneity and stability of the mixture;e)
Containers containing mixtures of test samples and reference materials (or diluents) are labeled, and, if possible, records of the homogeneity and stability of their contents are maintained;wwW.bzxz.Net
If a test exceeds 4 weeks, samples of each batch of test samples and reference materials should be analyzed to determine the appropriate shelf life;
h) Procedures are established for mixing materials to avoid misidentification or cross contamination. 5.10 Standard Operating Procedures
5.10.1 Purpose: To determine whether there are adequate written standard operating procedures for all significant aspects of the testing facility's operations. The use of written standard operating procedures is one of the most important management techniques for controlling the facility's operations, which directly address the routine elements of the tests performed by the testing facility.
The inspector should check that:
each area of the testing facility has ready access to a copy of the relevant, approved standard operating procedures; that there is a procedure for revising and updating the standard operating procedures; b
any modifications or changes to the standard operating procedures have been approved and dated; d)
a historical record of standard operating procedures is maintained; and that there are standard operating procedures that apply to, but are not limited to, the following: e
receiving of test samples and reference materials; determination of identity, purity, composition, and stability; labeling, handling, Samples, use and storage: - Use, maintenance, cleaning, calibration and validation of measuring instruments, computerized systems and environmental control equipment: Preparation of reagents and dosage preparation;
- Record keeping and reporting; Storage and reading of records and reports: - Preparation of areas containing test systems and environmental control: - Receipt, transfer, placement, characterization, labeling and management of test systems; - Handling of test systems before, during and at the end of the study, - Disposal of test systems;
Use of pesticides and cleaning agents;
- Implementation of a quality assurance program.
Implementation of the study
Implementation of the study: Verify that a written study plan exists and that the plan and the implementation of the study follow GLP principles. 5.11.1
The inspector shall check that: a) the research plan has been signed by the project leader; b) the project leader has signed his name and date on any changes to the research plan; the date on which the client agrees to the research plan is recorded (if applicable); c) measurements, observations and inspections are carried out in accordance with the research plan and relevant standard operating procedures; the results of measurements, observations and inspections are recorded directly, quickly, accurately and clearly, and the name (full name or abbreviation) and e)
f) Modification of original data, including data stored in computer, shall not cover the original traces, shall include the reason for modification and indicate the person responsible for modification and modification date;
Data generated or stored by computer are confirmed, and there are adequate procedures to prevent data loss or unauthorized modification; the computerized system used in the study is reliable, accurate and has been confirmed; h)
Any unexpected events recorded in the original data have been investigated and evaluated; 5
GB/T 22274.2—2008
j) The results in the interim or final study report are consistent and complete; they accurately reflect the original data. 5.12 Report of study results
5.12.1 Purpose: To determine whether the final report is prepared in accordance with the CLP principles. 5.12.2 When inspecting a final report, the inspector should check that: the principal investigator has acknowledged his or her responsibility for the validity of the study by signing and dating the final report and confirming that a) the study was conducted in accordance with GLP principles; b) if a report from a collaborating field is included, the other principal scientists have also signed and dated it; d) the report contains a signed and dated quality assurance statement: any modifications were made by the responsible individual; c) the report lists the location of the archive (including all retained samples, specimens, and raw data). 5.13 Storage and Retention of Records 5.13.1 Purpose: To determine whether the organization produces adequate records and reports and whether adequate provisions are in place for the safe storage and retention of these records and materials.
5.13.2 The inspector shall inspect
that a person responsible for archiving is designated:
archival facilities for the storage of the following materials: study plans, raw data (including data generated by terminated GLP studies), final b)
reports, retained samples, specimens, education and training records of personnel; c)
procedures for accessing archived materials:
procedures for limiting access to archives to authorized personnel only, and records of personnel authorized to access archives such as raw data and slides; d)
a list of materials removed and returned from the archival facility is maintained; f) records and materials are retained for the required or appropriate period of time; and care should be taken to prevent loss, fire, adverse environmental conditions, etc. 6 Study Audits
6.1 Inspections of test facilities often include study audits, which are reviews of ongoing or completed studies. Regulatory authorities also often require specific study audits, which may be conducted separately from the inspection of the test facility. Because there are so many different types of studies to be reviewed, and only one general guideline can be used, the inspector and others involved in the study review will often need to use their own judgment to determine the nature and scope of the review. The goal of a study review is to reconstruct the study by comparing the final report with the study plan, relevant standard operating procedures, raw data, and other archived materials.
6.2 In some cases, the inspector will need the help of other experts to conduct an effective study review, for example, if a tissue slide needs to be examined under a microscope.
6.3 When performing a study audit, the inspector should: a) obtain the name, work description, training and experience profile of the personnel selected to conduct the study (such as the project leader and key technical experts);
check whether there are sufficient personnel trained in the relevant fields of the study undertaken; b)
identify the various instruments or special equipment used in the study and check the calibration, maintenance and service records of these equipment; d)
review the records related to the stability of test samples, analysis of test samples and formulations, and analysis of raw materials; e) if possible, try to confirm the work assignments of the selected participating researchers through interviews to verify whether these personnel have time to complete the tasks specified in the study plan or report; f) obtain copies of all documents related to control procedures or ensuring the integrity of the study, including: - study plan; - standard operating procedures used when conducting the study; - record books, laboratory notebooks, files, work orders, printouts of computer stored data, etc.; when appropriate, review their calculation results; - final report.
GB/T 22274.2—2008
6.4 If animals (such as rodents and other mammals) are used in the study, the inspector should track a certain proportion of individual animals from the time they are shipped to the research facility to the time of the household inspection. Particular attention should be paid to the following records: a) animal weight, food and/or water intake, dosage formulation and administration, etc., b) clinical observations and autopsy findings: c) clinical chemistry; d) histopathology.
7 Completion of the inspection or study review
7.1 When the inspection of the research facility or the study review is completed, the inspector should discuss his findings with the representatives of the research facility at the closing meeting and should prepare a written report, such as the inspection report. 7.2 The inspection of any large facility may reveal some minor deviations from the principles of GLP, but generally, these deviations will not be so serious as to affect the validity of the studies conducted by the testing facility. In this case, it is reasonable for the inspector to report that the institution complies with the GLP principles according to the standards set by the GLP supervision department. However, the details of the deficiencies or defects found should be provided to the testing institution, and its senior management should be assured that corrective measures will be taken. The inspector needs to return to the institution after a period of time to verify that it has taken the necessary measures.3 If a significant deviation from the GLP principles is found during an inspection or study audit of a testing facility that, in the inspector's opinion, may have affected the validity of the study or other studies conducted at the facility, the inspector should report it to the GLP oversight unit. The actions taken by the oversight unit and/or management (as applicable) will be responsive to the nature and extent of the violation and the legal and/or regulatory requirements within the GLP compliance program.
7.4 Upon completion of a study audit conducted at the request of management, a comprehensive report on the audit findings should be prepared and submitted to the relevant management via the relevant GLP oversight unit. GB/T 22274.2-2008
National Standard of the People's Republic of China
Guidelines for the Supervision of Good Laboratory Practice
Part 2: Guidelines for the Performance of Laboratory Inspections
and Research Audits
GB/T 22274, 2—2008
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