Key Benefits:
The Prime Minister,
On the report of the Minister of Economy, Finance and Industry,
Considering Directive 2004/9/EC of the European Parliament and the Council of 11 February 2004 on the inspection and verification of good laboratory practices (BPL);
Having regard to Directive 2004/10/EC of the European Parliament and the Council of 11 February 2004 on the approximation of the legislative, regulatory and administrative provisions on the application of the principles of good laboratory practices and the control of their application for chemical testing;
Considering articles L. 253-1 et seq. of the rural code;
Considering articles L. 521-1 et seq. of the Environmental Code;
Having regard to amended Decree No. 61-501 of 3 May 1961 concerning units of measurement and control of measuring instruments;
In light of amended Decree No. 81-278 of 25 March 1981 establishing an inter-ministerial group of chemicals,
Decrete:
Sections 1, 2 and 2-1 of the above-mentioned Decree of 25 March 1981 are amended as follows:
I. - Article 1 is as follows:
"The interdepartmental group of chemicals is responsible for monitoring compliance with good laboratory practices, as set out in the appendices to this Order, of any testing laboratory located in French territory and declaring to apply good laboratory practices for conducting non-clinical tests for the assessment of human, animal and environmental effects on all chemicals other than the products referred to in section L. 5311-1 »
II. - Article 2 is as follows:
"The President of the Interdepartmental Chemicals Group is appointed by the Prime Minister's Order.
The group is composed of seven members, respectively designated by:
Minister for Health;
Minister of Labour;
Minister for the Environment;
Minister responsible for the economy;
Minister for Agriculture;
Minister for Industry;
The Minister for Research.
The departments concerned may designate an expert from one of the French health security agencies to represent them on an ad hoc or permanent basis.
The Chairperson may appeal to the competent personalities of which he considers it useful to participate in the work of the group.
The General Secretariat is provided by the Corporate Directorate of the Department of Industry.
Each year, the Interdepartmental Chemicals Group prepares a report on the applications of good laboratory practices in France for the tests referred to in Article 1. This report contains a list of laboratories inspected, the date on which these inspections were conducted and a brief summary of the findings of the inspections. It is transmitted to the relevant services of the European Commission and the Organisation for Economic Co-operation and Development (OECD). »
III. - Article 2-1 is as follows:
"Every laboratory declaring to apply good laboratory practices for the tests referred to in Article 1 shall apply for compliance with the interdepartmental chemical group, with a copy to the "French Accreditation Committee or another accreditation body signatory to a mutual recognition agreement.
Based on the results of the inspections and audits carried out by the accreditation body, the interdepartmental chemical group finds whether the good laboratory practices described in the annexes to this Order have been implemented.
At the conclusion of this review, and if satisfactory, the interdepartmental group of chemicals may be the guarantor of the declaration of a laboratory which states that it and the tests carried out by it are in conformity with the good laboratory practices according to the provisions contained in the two annexes to this Order. »
The Schedule to the Decree of 25 March 1981 is replaced by the annexes to this Order.
The Minister of Employment, Social Cohesion and Housing, the Minister of Economy, Finance and Industry, the Minister of National Education, Higher Education and Research, the Minister of Health and Solidarity, the Minister of Agriculture and Fisheries, the Minister of Ecology and Sustainable Development, the Minister Delegate for Employment, Work and the Delegate Minister of Education,
A N N E X E I
The provisions for the inspection and verification of LPGs contained in Parts A and B are those set out in Annexes I (Guides for Systems for the Verification of Good Laboratory Practices) and II (Guides for the Conduct of Inspections for the Installation of Tests and Studies) of the decision-recommendation of the OECD Council on Compliance with Principles of Good Laboratory Practices (C[89] 87
PART A
Revised audit systems guidelines
BPL compliance
Definitions of terms
The following definitions are added to the terminology in Appendix II to this Order:
- "BPL principles": principles of good laboratory practices compatible with OECD principles of good laboratory practices, as set out in Appendix II to this decree;
- "BPL compliance verification": periodic inspection of test facilities and/or verification of studies conducted to ensure compliance with the BPL principles;
- "national compliance program": a specific device established by the IPPC to verify compliance with LPG by testing facilities located in its territory, by means of inspection and study checks;
- "BPL Verification Authority": the IPPC is the supervisory authority responsible for monitoring compliance with good laboratory practices of any testing facility located in French territory and declaring to apply the LLP for non-clinical testing for the assessment of human, animal and environmental effects on all chemicals other than products referred to in section L. 5311-1 COFRAC is the logistic support of the IPPC for the LPG monitoring program;
- "test installation inspection": on-site review of the procedures and methods used in the testing facility to assess the degree of compliance with the BPL principles. During the inspections, the administrative structure and standard operating procedures of the test facility are reviewed, the technical staff of supervision is interviewed, the quality and integrity of the data obtained by the facility are assessed and reported in a report;
- "study check": comparison of raw data and reports associated with the interim or final report, to determine whether the raw data were accurately reported, to verify whether the tests were conducted in accordance with the study plan and standard operating procedures, to obtain additional information not included in the report and to determine whether the methods used to obtain the data were not likely to be valid;
- "Inspector": person who conducts inspection of the testing facility and the study verification on behalf of the IPPC;
- " degree of compliance with LPGs": degree of adherence to the LPG principles of a test facility, which is assessed by the GMP;
- "regulatory authority": a national body with legal competence for chemicals control issues.
National LPG compliance programme
The objective of the LLP compliance verification is to determine whether the test facilities applied, for the conduct of their studies, the principles of good laboratory practices and whether they are able to guarantee sufficient quality for the data obtained.
The IPPC publishes detailed information on LPG activity in the form of a laboratory good practice program.
The IPPC Laboratory Good Practices Compliance Program applies to chemicals with the exception of products referred to in section L. 5311-1 of the Public Health and Veterinary Drugs Code referred to in section L. 5141-1 of the Public Health Code that fall within the competence of health safety agencies (respectively AFSSAPS and AFSSA); It includes:
- the recall of applicable legislative and regulatory provisions for inspection, as to access to test facilities and data held by them (including specimens, standard operating procedures, any other documentation ...);
- description of the procedure followed by testing facilities to be included in the annual control program;
- guidance on inspections of testing facilities implemented by COFRAC which may be:
- either general inspections of the test facility, or site inspections and/or audits of one or more ongoing or already completed studies;
- either inspections of test facilities and special studies checks made at the request of another regulatory authority;
- guidance on the periodicity of inspections and the assessment of inspections of the previous year;
- measures that may be taken as part of the monitoring of test facilities inspections and study verifications.
Monitoring of test facility inspections
and Study Audits
When an inspection of testing or study verification has been completed, the inspector must prepare a written report on his findings.
The IPPC shall consider these reports at its periodic meetings with a view to establishing a decision to comply with the LPG principles or to take the necessary measures to ensure compliance with the facility:
If no deviation is found, or only a minor deviation, the IPPC may:
- publish a statement indicating that the test facility was inspected and that its operation was estimated in accordance with the BPL principles. The date of the inspection must be included and, where applicable, the test categories inspected in the test facility at that time must be included; these statements may be used to provide information to the (national) LPG verification authorities in other OECD countries,
and/or
- provide a detailed report on the findings to the regulatory authority that requested the study audit.
In all cases, if minor deviations are found, the test facility is required to correct them.
When serious deviations are found, the IPPC Chair may:
- deny or suspend recognition of compliance with the principles of LPG, the decision being motivated by deficiencies or anomalies identified and likely to alter the validity of the studies conducted in the test facility;
- exclude the trial installation of the annual compliance programme and inform the Commission and the competent authorities of the Member States of the discrepancies observed;
- bring an action before the courts, provided that the situation warrants it and that legal or administrative procedures permit it.
Appeal procedures
Problems or differences of views between inspectors and the management of test facilities are normally resolved during the inspection of the test facility or the study verification. However, it is not always possible to reach an agreement. In the event of a challenge to the notice issued on the inspection report, the testing facility is invited to provide its views on the findings of the test installation inspection or study verification with a view to monitoring compliance with LPG with the IPPC Chair. The application is reviewed during a periodic IPPC meeting.
PART B
Revised guidelines for conducting inspections
testing and testing facilities
Introduction
The purpose of this part of this annex is to provide mutually acceptable guidelines by OECD member countries for the conduct of inspection of test facilities and study verifications. It mainly deals with inspections of test facilities, which are largely dedicated to inspectors responsible for verifying compliance with LPGs. Test facility inspections most often include a study check or "review"; these studies audits should also be conducted from time to time, at the request, for example, of a regulatory authority. At the end of this annex, there are general indications on the conduct of studies audits.
Test facility inspections are designed to determine the degree of compliance of test facilities and studies with the BPL principles and to verify the integrity of the data to ensure that the results obtained are of sufficient quality for national regulatory authorities to conduct an assessment and make decisions. Inspections result in reports that describe the degree of compliance of testing facilities with the BPL principles. Test facilities must be inspected on a regular basis on a 15-month routine basis so that LPG compliance records can be compiled and maintained by testing facilities.
Further details on most of the points raised in this part of the annex can be obtained by referring to consensus documents on OECD LPGs (e.g. on the role and responsibilities of the study director).
Definitions of terms
Test facility inspections
Inspections to verify compliance with the BPL principles may be carried out in any testing facility where, for regulatory purposes, data on the safety of products for health and the environment are obtained. Inspectors may be required to verify the physical, chemical, toxicological or ecotoxicological properties of a substance or preparation. In some cases, inspectors may need the assistance of special disciplines specialists.
Given the wide variety of facilities (both the layout of the premises and the administrative structure) and the various types of studies encountered during the inspections, the judgment of inspectors responsible for assessing the degree and extent of compliance with the principles of BPL is essential. However, the Inspectors must strive to adopt a uniform approach to assess whether, in the case of a specific test facility or a particular study, an adequate degree of compliance is achieved for each LPG principle.
In the following sections, guidance is provided on various aspects of the testing facility, including its staff and procedures that are likely to be reviewed by inspectors. In each of the sections, the subject-matter is indicated and the specific points that could be examined during a test installation inspection are listed as an example. These lists are not intended to be exhaustive and should not be considered as such.
Inspectors should not be concerned about the scientific plan of the study, nor about the interpretation of the results obtained in studies on risks to human health and the environment. These issues are the responsibility of the regulatory authorities to which the data are submitted for regulatory purposes.
Test facility inspections and study checks inevitably disrupt the normal operations of testing facilities. The inspectors must therefore perform their work in a methodical manner and according to a carefully established plan and, to the extent possible, take into account the wishes of the management of the testing facility for the hours to which they may travel to certain parts of the facility.
During inspections of test facilities and study checks, inspectors have access to confidential data with commercial value. It is essential that they ensure that this information is viewed only by authorized personnel.
Inspection procedures
Inspection
Purpose: To inform the inspector of the inspection facility, including its administrative structure, the layout of its premises and the range of studies carried out there.
Before conducting a test installation inspection or study verification, inspectors must familiarize themselves with the facility they will visit. They must review all existing information on the installation. This information may include previous inspection reports, a facility plan, organization charts, study reports, test protocols, and a staff curriculum vitae (VC). These documents will provide information on:
- the nature, dimensions and layout of the installation;
- the range of studies that may be encountered during the inspection, and
- the administrative structure of the facility.
In particular, inspectors should note the potential deficiencies of previous test facilities inspections.
Test facilities may be informed of the date and time of arrival of inspectors, the purpose and duration of the inspection visit. The test facilities will be able to ensure that the staff concerned is present and that the appropriate documentation is available. In cases where specific documents or records are to be examined, it may be useful to inform the pre-test facility so that the inspector can immediately communicate them to the inspector during his visit.
Preliminary meeting
Purpose: inform management and staff of the installation of the reasons for the testing installation inspection or study verification that will take place and identify the areas of the facility, the studies selected for verification, the documents and staff members likely to be affected.
The administrative and practical details of a test installation inspection or study verification must be examined with the facility management at the beginning of the visit. At the preliminary meeting, inspectors must:
- to present in their outline the object and scope of their visit;
- indicate the documentation they need to conduct the inspection of the testing facility, such as lists of ongoing and completed studies, studies plans, standardized operating procedures, study reports, etc. It is at this stage that it is necessary to decide on access to the relevant documents and, where appropriate, to make arrangements for their reproduction;
- request details or information on the administrative structure (organization) and personnel of the facility;
- request information on the conduct of studies that are not subject to the LPGs in the areas of the LPG testing facility;
- make a first determination of the parts of the test facility affected by the inspection of the test installation;
- describe the documents and specimens that will be required for the study (the studies) in progress or completed selected for a study audit;
- indicate that a closing meeting will take place at the end of the inspection.
Before conducting a test installation inspection further, it is desirable that the inspector contact the quality assurance facility (QA) service.
In general, inspectors find it useful to be accompanied by a member of the internal service responsible for quality assurance during the visit of a facility.
Inspectors may request that a room be reserved for them to review documents, and for other activities.
Organization and staff
Purpose: determine whether the testing facility has qualified personnel, staff resources and support services sufficient for the diversity and number of studies undertaken; verify that the administrative structure is appropriate and that management has put in place a health training and monitoring policy for its staff, adapted to the studies undertaken in the facility.
Management should be invited to provide certain documents, such as:
- a plan of the premises;
- the organization charts of the management of the facility and its scientific organization;
- staff CVs involved in the category(s) of studies selected for verification;
- list(s) of ongoing and completed studies as well as information on the nature of the study, start and completion dates, test systems, methods of application of the test element and the name of the study director;
- the health monitoring policy of staff;
- job descriptions and records on staff training programmes;
- an index of the standard operating modes of the installation;
- the specific standard operating procedures in relation to the studies or procedures inspected or verified;
- the (the) list(s) of the principals of studies and donors involved in the audited studies.
The inspector must check, in particular:
- lists of ongoing and completed studies to assess the volume of work undertaken by the testing facility;
- the identity and qualifications of the study directors, the quality assurance officer, and other staff members;
- the existence of standard operating modes for all relevant test areas.
Quality Assurance Program
Purpose: determine whether management has appropriate systems to ensure that studies are conducted in accordance with BPL principles.
The Quality Assurance Service Manager must be invited to demonstrate the systems and methods for the inspection and verification of the quality of the studies, as well as the system used to record the observations made during the quality verification. Inspectors must check:
- the qualifications of the AQ official and all the personnel of the service under his direction;
- the independence of the AQ service in relation to the staff involved in the studies;
- how the AQ service program and performs the inspections, and checks the critical phases identified in a study, as well as the resources available for quality inspection and verification activities;
- the provisions for the verification on the basis of samples in case the duration of the studies is so brief that it is impossible to check each of them;
- the extent and accuracy of quality assurance checks during the practical realization of the study;
- the extent and accuracy of quality assurance checks applied to the routine tasks of the testing facility;
- the quality assurance procedures applicable to the verification of the final report, in order to ensure that it is consistent with the raw data;
- the notification to the management, by the AQ service, of problems that affect the quality or integrity of a study;
- measures taken by the AQ service when deviations are found;
- the role of the AQ (if applicable) in the event that studies are carried out in part or in whole in subcontracting laboratories;
- the contribution (if applicable) of the AQ service to the review, revision and updating of standard operating procedures.
Facilities
Purpose: To determine whether the dimensions, layout and location of the test facility, both inside and outside, allow it to meet the requirements of the studies undertaken.
The inspector must check:
- that the layout of the facility allows sufficient separation of the various activities so that, for example, test elements, animals, diets, pathological specimens, etc., of a study cannot be confused with those of another;
- that there are procedures for monitoring and monitoring environmental conditions and that they operate appropriately in the most important areas, such as animalry and other rooms reserved for biological testing systems, testing areas and laboratory areas;
- that the general maintenance of the various facilities is sufficient and there are pest control procedures, if necessary.
Care, accommodation and system containment
biological test
Purpose: To determine whether, in the case of animal studies or other biological test systems, the installation of tests has appropriate equipment and sufficient conditions to ensure their care, accommodation and containment, so as to prevent stress and other problems that could affect the test systems and thus the quality of the data.
A test facility may carry out studies requiring various animal or plant species as well as microbiological systems or other cellular or infra-cellular systems. The type of test systems used determines the care, housing and containment aspects that the inspector must verify. By relying on his judgment, the inspector checks according to the test systems:
- that facilities are adapted to the biological test systems used and the test requirements to be performed;
- that provisions are intended to quarantine animals and plants introduced into the facility, and that they function satisfactorily;
- that provisions are provided to isolate animals (or other elements of a test system, if any) that are known or suspected to be sick or disease-bearing;
- that appropriate control and records on health, behaviour or other aspects, depending on the characteristics of the test system be provided;
- that the equipment intended to ensure the environmental conditions required for each biological test system is adequate, well maintained and effective;
- that animal cages, racks, tanks and other receptacles, as well as other accessories are maintained in a sufficient state of cleanliness;
- that analyses to verify environmental conditions and support systems are carried out as required;
- that there are devices for the removal and disposal of animal waste and residues of test systems and that these devices are used to minimize infestation by parasites, odours, disease risks and environmental contamination;
- that storage areas are provided for animal foods or equivalent products, for all test systems; that these areas are not used to store other materials such as test substances, pest control chemicals or disinfectants, and that they are separated from areas containing animals or other biological testing systems;
- that stored foods and bedding must be protected from adverse environmental conditions, infestation and contamination.
Devices, materials, reagents and specimens
Purpose: Determine whether the testing facility has equipment in good working condition, appropriately located, in adequate quantity and capacity to meet the requirements of the tests performed therein and ensure that: materials, reagents and specimens are properly labelled, used and stored.
The inspector must check:
- that the appliances are clean and in good working condition;
- that records have been maintained on the operation, maintenance, verification, calibration and validation of measuring equipment and equipment (including computer systems);
- that materials and chemical reagents are correctly labeled and stored at the right temperature and that expiry dates are respected. Reagent labels should indicate their origin, nature and concentration and/or other relevant information;
- that the identification of specimens clearly specifies the test system, the study carried out, the nature and the date of sampling of the specimen;
- that the equipment and materials used do not significantly alter the test system.
Test systems
Purpose: determine whether appropriate procedures exist for the handling and control of the various test systems required by the studies undertaken in the facility, such as chemical, physical, cellular, microbiological, plant or animal systems.
Physical and chemical testing systems
The inspector must check:
- that the stability of the test and reference elements has been determined in accordance with the possible requirements of the study plan, and that the reference elements referred to in the test plans have been used;
- that, in automated systems, the data obtained in the form of graphs, recording curves or printer outputs were classified as raw and archived data.
Biological Test Systems
Taking into account the relevant points for the care, housing and containment of biological testing systems, the inspector must verify:
- that the test systems correspond to what is defined in the study plans;
- that the test systems are properly identified, and if necessary and appropriate, in a univocal manner throughout the study; that there are records on receipt and the number of test systems received used, replaced or rejected, largely supported by supporting documentation;
- that the dwellings or receptacles of the test systems are correctly identified with all necessary information;
- that there is sufficient separation between studies conducted on the same animal species (or the same biological test systems) but with different substances;
- that the separation of animal species (and other biological test systems) is ensured satisfactorily in space and time;
- that the environment of biological test systems is such that it is defined in the study plan or in normal operating modes, particularly with regard to temperature or light/black cycles;
- that records on the reception, handling, housing or containment, care and assessment of the health status are adapted to the characteristics of the test systems;
- that there are records on the examination, quarantine, morbidity, mortality, behaviour, as well as on the diagnosis and treatment of conditions of animal and plant testing systems or other similar aspects appropriate to each biological test system;
- that provisions are provided for the satisfactory elimination of test systems after testing.
Test and reference elements
Purpose: Determine whether the testing facility has procedures designed to: (i) ensure that the nature, power, quantity and composition of the test and reference elements comply with the requirements and (ii) correctly receive and store the test and reference elements.
The inspector must check:
- that there are records on the receipt (including the identity of the person responsible for it), the handling, sampling, use and storage of the test and reference elements;
- that the receptacles of the test and reference elements are correctly labelled;
- that the storage conditions are capable of preserving the concentration, purity and stability of the test and reference elements;
- where applicable, records are required to determine the identity, purity, composition and stability of the test and reference elements and to prevent contamination;
- where applicable, there are procedures (standard operating procedures) for the determination of homogeneity and stability of mixtures containing test and reference elements;
- where appropriate, that the receptacles containing mixtures (or dilutions) of the test or reference elements are labelled and records are kept on the homogeneity and stability of their contents;
- if the duration of the test is greater than four weeks, that samples of each batch of the test and reference elements have been taken for analysis and have been retained for an appropriate period of time;
- that procedures are planned for mixing elements so as to avoid identification errors and reciprocal contamination.
Standard operating procedures
Purpose: Determine whether the testing facility has standard operating procedures written for all important aspects of its operations, given that this is one of the main means for management to control the operation of the facility. These operating modes have a direct connection to the most common aspects of the tests conducted by the testing facility.
The inspector must check:
- that each area of the test facility has immediate access to approved copies of appropriate standard operating procedures;
- that there are procedures for the revision and updating of standard operating procedures;
- that any amendment or change in standard operating procedures has been approved and dated;
- that chronological records of standard operating modes are maintained;
- that standard operating procedures are available for the following activities, and possibly for other activities:
(i) reception, identification, purity, composition and stability, labelling, handling, sampling, use and storage of test and reference elements;
(ii) use, maintenance, cleaning, calibration and validation of measuring equipment, computer systems and ambient conditions control equipment;
(iii) preparation of reagents and dosage of preparations;
(iv) record-keeping, reporting, storage and consultation of records and reports;
(v) preparation and regulation of ambient conditions of areas containing the test system;
(vi) reception, transfer, location, characterization, identification and maintenance of test systems;
(vii) Handling of test systems before, during and at the end of the study;
(viii) elimination of test systems;
(ix) use of pest control agents and cleaner agents;
(x) Quality Assurance Program operations.
Realization of the study
Purpose: verify that there are written study plans and that the plans and course of studies are in accordance with the principles of BPL.
The inspector must check:
- that the study plan was signed by the study director;
- all amendments to the study plan were signed and dated by the study director;
- where applicable, that the date of approval of the study plan by the donor of order has been recorded;
- that the measurements, observations and examinations are carried out in accordance with the study plan and appropriate standard operating procedures;
- that the results of these measures, observations and reviews have been recorded in a direct, timely, accurate and legible manner and that they have been signed (or paraphrased) and dated;
- that all changes to raw data, including computer memory, do not overlap with previous records, indicate the reason, the date of the modification and the identity of the person involved;
- that the data obtained by computer or stored in memory are identified and that the backup or protection procedures against unauthorized amendments are appropriate;
- that the computer systems used in the study are reliable, accurate and validated;
- that all unforeseen events recorded in the raw data have been studied and evaluated;
- that the results presented in the (provisional or final) reports of the study are consistent and comprehensive and that they correctly reflect the raw data.
Summary of results of the study
Purpose: verify that final reports are prepared in accordance with the BPL principles.
When examining a final report, the inspector must verify:
- that it is signed and dated by the study director to indicate that it takes responsibility for the validity of the study and confirms that the study was conducted in accordance with the principles of BPL;
- that it is signed and dated by other major researchers, if reports from the major researchers in the disciplines to which the study draws are included;
- that a statement on quality assurance is included in the report, signed and dated;
- that any amendments have been made by the competent staff;
- that the report lists the locations in the "architects" of all samples, specimens and raw data.
Storage and retention of documents
Purpose: determine whether the facility has established adequate records and reports and whether appropriate arrangements have been made to ensure the safe storage and storage of documents and materials.
The inspector must check:
- that a person has been designated as responsible for the archives;
- the "archives" rooms for the storage of study plans, raw data (including those obtained in the LPG studies that were interrupted), final reports, samples and specimens, and registers on the qualifications and training of staff;
- the procedure for consulting the archived material;
- procedures that limit access to records to authorized personnel and records where the names of persons with access to raw, slide, etc. are listed;
- that an inventory of materials removed from the archives, or on the other hand returned, is held;
- that documents and materials are kept during the necessary or appropriate time and that measures are taken to prevent them from being lost or damaged by fire, harmful ambient conditions, etc.
Audits
In general, inspections of test facilities include, inter alia, audits of studies that consist of ongoing or completed studies. Special studies checks are also often required by regulatory authorities; these may be performed independently of inspection of test facilities. Due to the wide variety of studies that can be verified, only general indications should be given, and inspectors and other persons involved in the audit should always exercise their judgment on the nature and scope of the examinations they will conduct. Their purpose is to reconstruct the study by comparing the final report to the study plan, standard operating procedures, raw data and other archived documents. In some cases, inspectors may need the help of experts to effectively conduct a study check - for example, when they need to examine the tissue cut microscope.
When conducting a study check, the inspector must:
- obtain the name, job description and summary of the training and experience of some staff involved in the study or studies, such as the study director and the main researchers;
- ensure that there is a sufficient number of people trained in the areas related to the study or studies undertaken;
- determine the various special equipment or equipment used in the study and review records relating to the calibration, maintenance and service of such equipment;
- review records relating to the stability of test elements, the analysis of these elements and preparations, and food analyses;
- try to determine, to the extent possible through an interview, the tasks assigned to persons chosen to participate in the study, whether they have sufficient time to perform the tasks assigned to them in the study plan;
- to obtain copies of all documents describing the control procedures or forming an integral part of the study, including:
(i) the study plan;
(ii) the standard operating procedures in effect at the time of the study;
(iii) records, laboratory books, records, worksheets, printer outputs, etc.; verification of calculations, if applicable;
(iv) the final report.
In studies for which animals (e.g. rodents and other mammals) are used, the inspector must examine what happens from a certain percentage of animals since their arrival at the installation of tests until their autopsy. Special attention should be paid to cases involving:
- the body weight of animals, quantities of ingested water and food, preparation and administration of doses, etc.;
- clinical observations and autopsy results;
- biological examinations;
- Pathology.
End of Study Inspection or Audit
At the end of the inspection, the inspection team discusses its observations and conclusions with the trial facility representatives during a closing meeting.
At the end of this inspection, a report is prepared and transmitted to the test facility and to the IPPC. This inspection report consists of non-compliance sheets and general and technical conclusions regarding compliance with the installation's BPL principles. The non-compliance slips present the deviations from the BPL principles repository and the corrective action proposals made by the facility to address these deviations.
If an inspection reveals a major deviation from the LPG principles, which could compromise the integrity or authenticity of the audited study, or other studies carried out in the facility, it is clearly notified in the inspection report provided to the testing facility and the PWGSC.
The actions taken by the IPPC will depend on the nature and extent of the failure to comply with the LPG principles.
After the inspection of the test facility, a certificate of conformity assessment to the BPL principles is established, including the inspection date and compliance status of the facility.
When a study verification has been conducted at the request of a competent supervisory authority, a full report is prepared and sent to that authority concerned by the IPPC.
A N N E X E I
OECD PRINCIPLES OF PRACTICES
DE LABORATOIRE (BPL)
Section I
Introduction
Preface
Public authorities and industry attach great importance to the quality of non-clinical health and environmental safety studies on which hazard assessments are based. This is why OECD member countries have set criteria for the achievement of these studies. Desirous of avoiding differences in application modalities to hinder international trade in chemicals, OECD member countries have continued to harmonize international test methods and good laboratory practices. In 1979 and 1980, an international group of experts, formed under the special programme on chemicals control, established the "OECD principles of good laboratory practices" (BPL), summarizing the management methods, scientific practices and experience of various national and international bodies. These BPL principles were adopted by the OECD Council in 1981, as an annex to the Commission's decision on the mutual acceptance of data for the assessment of chemicals (C[81] 30 final).
In 1995 and 1996, a new group of experts was established to review and update these principles. This document is the result of the consensus reached by this group. It cancels and replaces the principles initially adopted in 1981.
The purpose of these principles is to promote the availability of quality test data. A comparable quality of test data is the very basis of mutual acceptance of this data by countries. If each country can reliably rely on test data obtained in other countries, it will be possible to avoid repeating the tests and thus save time and resources. The application of these principles should help prevent the creation of technical barriers to trade and further improve the protection of human health and the environment.
1. Scope
These principles relating to good laboratory practices will need to apply to non-clinical safety tests performed on elements contained in pesticides, additives for human and animal food and industrial chemicals. These test elements are often synthetic chemicals, but may have a natural or biological origin and may be organisms living under certain circumstances. The tests carried out on these elements are intended to provide data on their properties and/or their safety from the perspective of human health and/or the environment.
Non-clinical safety studies related to health and the environment covered by the principles of good laboratory practices include research at the laboratory, greenhouse and field level.
Except as otherwise provided by specific provisions, these principles of good laboratory practices apply to all non-clinical safety studies related to the health and environment required by regulation for the purposes of registration or authorization of pesticides, additives for human and animal food, and for the purposes of the regulation of industrial chemicals.
2. Terminology
2.1. Good laboratory practices
Good laboratory practices are a quality assurance system for the organization of non-clinical safety studies related to health and the environment and the conditions under which such studies are planned, conducted, controlled, recorded, archived and disseminated.
2.2. Terms for the organization of a test facility
1. The test facility includes individuals, premises and equipment that are necessary to carry out the non-clinical safety study related to health and the environment. For multisite studies, conducted at several sites, the test facility includes the site where the study director is located and all other test sites, which can be considered individually or collectively as test facilities.
2. The test site includes the location(s) on which one or more phases of a particular study are performed.
3. The direction of the test facility shall include the person(s) invested with the authority and official responsibility of the organization and operation of the test facility, in accordance with these principles of good laboratory practices.
4. The direction of the test site includes the person(s) (if identified) responsible for ensuring that the stage(s) of the study, of which they are responsible, is conducted in accordance with these principles of good laboratory practice.
5. The principal is the legal entity that orders, sponsors or submits a non-clinical safety study related to health and the environment.
6. The Director of the study is the person responsible for the overall conduct of the non-clinical safety study related to health and the environment.
7. The principal conductor of the tests is the person who, in the case of a multisite study, exercises, on behalf of the Director of the study, well defined responsibilities for the phases of the study that are delegated to him. The Director of the Study shall not delegate to the principal(s) responsible for the overall conduct of the study, in particular with regard to approving the study plan, with its amendments, and the final report, and ensuring compliance with all relevant principles of good laboratory practices.
8. The quality assurance program is a specific system, encompassing the corresponding staff, which is independent of the conduct of the study and aims to provide the management of the testing facility with assurance that these principles of good laboratory practices are well respected.
9. Standard operating procedures are operating modes supported by documents that describe how to conduct tests or works that are not normally included in the study plan or in the test guidelines.
10. The master plan (time plan of studies) is a compilation of the information to assist in the assessment of the workload and the monitoring of the studies carried out in a test facility.
2.3. Non-clinical Safety Study Terms
related to health and the environment
1. A non-clinical safety study related to health and the environment, referred to as simply a "study" below, consists of an experience or a set of experiments in which a test element is examined, in the laboratory or in the environment, with a view to obtaining data on its properties and/or safety intended to be submitted to the relevant regulatory authorities.
2. A short-term study is a short-term study carried out with widespread, widely used techniques.
3. The study plan is a document that defines the objectives of the study and the experimental devices necessary for its conduct, with any possible amendments.
4. An amendment to the study plan is a deliberate amendment to this plan after the date of the study.
5. A deviation from the study plan is a non-deliberate deviation from this plan, occurring after the date of the study.
6. The test system means any biological, chemical or physical system, or any combination thereof, which is used in a study.
7. The raw data represent all the records and original documents of the test facility or the compliant copies of them, which are the result of the original observations and work carried out in a study. The raw data may also include, for example, photographs, copies on microfilm or microfiche, data on computer support, tape observations, automatic data recordings or any other means of data retention deemed to be able to securely store information for a certain period of time, as indicated in section 10 below.
8. A specimen means any material taken from a test system for examination, analysis or conservation.
9. The date of the beginning of the experiments is the date on which the first particular data are obtained.
10. The date of the end of the experiments is the last date on which data from the study are obtained.
11. The start date of the study is the date on which the study director signs the study plan.
12. The date of completion of the study is the date on which the study director signs the final report.
2.4. Test element terms
1. A test element is an article that is the subject of a study.
2. A reference element ("control element") is any item used to provide a comparison basis with the test element.
3. A lot represents a specified quantity of a test or reference element that is produced during a well-defined manufacturing cycle so that it normally has a uniform character and must be designated as such.
4. A vehicle represents any agent used as a carrier medium to mix, disperse or solubilize the test or reference element to facilitate its administration or application to the test system.
Section II
Principles of Good Laboratory Practice
1. Organization and personnel of the test facility
1.1. Responsibilities of the direction of the test facility
1. The management of any test facility must ensure that these principles are respected for good laboratory practices in the facility and ensure that the proper execution of the tasks required for compliance is carried out by any subcontractor whose activity involves part of the study.
2. At the very least:
(a) Ensure the existence of a declaration that designates the person(s) exercising, in a test facility, the management responsibilities as defined by these principles of good laboratory practices;
(b) Ensure that a sufficient number of qualified individuals, as well as appropriate facilities, equipment and materials, are available to ensure that the study is conducted in a timely and appropriate manner;
(c) Ensure the conduct of a record containing the qualifications, training, experience and description of the tasks of all professional and technical staff;
(d) Ensure that staff understand clearly the tasks that they need to perform and, where appropriate, train them in these tasks;
(e) Ensure that relevant and technically valid standard operating procedures are defined and monitored, and approve any new or revised standard operating procedures;
(f) Ensure the existence of a quality assurance program with a staff specifically affected and verify that the responsibility for quality assurance is assumed in accordance with these principles of good laboratory practice;
(g) Verify that, for each study, a person with the required qualifications, training and experience is appointed Director of the study by management prior to the initiation of the study. The replacement of the study director must be in accordance with established procedures and must be supported by documents;
(h) Verify, in the case of a multisite study, that a principal conductor of the tests having the required training, qualifications and experience is designated, where appropriate, to supervise the or phases of the study that are delegated to him. The replacement of a primary test officer shall be in accordance with established procedures and must be supported by documents;
(i) Ensure that the study director approves the study plan in full knowledge of the case;
(j) Verify that the study director has made the approved study plan available to quality assurance personnel;
(k) Ensure the maintenance of a chronological file of all standard operating modes;
(l) Ensure that a person is designated as responsible for the management of the archives;
(m) Ensure that a master plan is maintained;
(n) Ensure that supplies received by the testing facility meet the requirements for their use in a study;
(o) Verify, in the case of a multisite study, that there is a transparent communication system between the Director of the study, the principal(s) of the tests, the managers of the quality assurance program(s) and the study staff;
(p) Verify that the test elements and reference elements are correctly characterised;
(q) Establish procedures to ensure that computer systems are appropriate to the intended objective and are validated, used and maintained in accordance with these principles of good laboratory practices.
3. When one or more phases of a study take place on a test site, the site direction (if one has been designated) will assume the responsibilities described above, with the exception of those listed in 1.1.2 (g, i, j and o).
4. Responsibilities of the Study Director.
1. The Director of the study is solely responsible for the control of the study and is responsible for the overall conduct of the study and the final report.
2. In particular, the study director has the following responsibilities, the list of which is not limited. He must:
(a) To approve, by a dated signature, the plan of the study and any amendment to it;
(b) Ensure that quality assurance personnel have, in a timely manner, a copy of the study plan and any possible amendments and communicate effectively with quality assurance personnel on the basis of the needs of the study;
(c) Ensure that the staff performing the study has many plans for the study, with their amendments and standard operating procedures;
(d) Verify that the study plan and the final report in the case of a multisite study describe and define the role of each principal test officer and site or test facility involved in the course of the study;
(e) Ensure compliance with the procedures described in the study plan, assess and report the impact of any deviation from the plan on the quality and integrity of the study, and take appropriate corrective action, if any; see deviations from normal operating modes during the completion of the study;
(f) Ensure that all raw data obtained are fully supported by documents and recorded;
(g) Verify that the computer systems used in the study have been validated;
(h) Sign and date the final report in order to indicate that it accepts responsibility for the validity of the data and to clarify the extent to which the study complies with these principles of good laboratory practices;
(i) Ensure that the study plan, final report, raw data and supporting documentation are transferred to the archives after completion (including inclusion) of the study.
1.2. Responsibilities of the principal conductor
The principal conductor of the tests will ensure that the phases of the study that are delegated to him are conducted in accordance with the applicable principles of good laboratory practices.
1.3. Responsibilities of study staff
1. All staff involved in the conduct of the study must be well informed of the parts of the principles of good laboratory practices applicable to their participation in the study.
2. The study staff will have access to the study plan and standard operating procedures that apply to their participation in the study. Its responsibility is to comply with the instructions given in these documents. Any deviation from these instructions shall be supported by documents and reported directly to the Director of the study or, where applicable, to the principal test officers.
3. It is the responsibility of all study staff to record raw data in a timely and accurate manner, in accordance with these principles of good laboratory practices, and to assume responsibility for the quality of such data.
4. The study staff must take the necessary hygiene precautions to minimize the risk to which it is exposed and to ensure the integrity of the study. It must notify the competent persons of any state of health or affection that it is aware of and may affect the study, so that the staff members concerned may be excluded from the operations where their intervention may adversely affect the study.
2. Quality Assurance Program
2.1. General
1. The test facility must have a quality assurance program using any useful document, which allows to verify that the studies are conducted in accordance with these principles of good laboratory practice.
2. The quality assurance program must be entrusted to one or more persons, designated by the management and directly responsible to the management, who have the experience of testing methods.
3. These persons must not participate in the completion of the study under the program.
2.2. Responsibilities of quality assurance personnel
Quality assurance personnel are responsible for the following tasks, which are not limited to:
(a) Keep copies of all approved standard study plans and operating procedures that are used in the test facility and have access to an updated copy of the master plan;
(b) Verify that the study plan contains the information necessary to respect these principles of good laboratory practices. This verification should be supported by documents;
(c) Conduct inspections to determine whether all studies are conducted in accordance with these principles of good laboratory practice. Inspections must also determine whether standard study plans and operating procedures have been made available to the study staff and are respected.
These inspections may be of three types, as specified in the standard operating procedures of the quality assurance program:
- inspection of the study;
- inspection of the facility;
- process inspections.
Records of such inspections shall be kept;
(d) Review final reports to confirm that methods, operating procedures and observations are faithfully and fully described and that the results recorded accurately and fully reflect the raw data of the studies;
(e) Report promptly in writing any inspection results to the direction and director of the study, as well as to the principal conductors and the respective directions, if any;
(f) Prepare and sign a statement, which will be included in the final report and will clarify the nature of the inspections and the dates on which they were conducted, including the phase(s) of the study being inspected, as well as the dates on which the results of the inspections were communicated to the management and the director of the study, as well as to the principal investigator(s) of the tests, as appropriate. This statement will also confirm that the final report reflects the raw data.
3. Facilities
3.1. General
1. Through its dimensions, construction and location, the test facility must meet the requirements of the study and minimize disruptions that may affect the validity of the study.
2. The design of the test facility must allow sufficient separation of the various activities, so as to ensure the correct execution of each study.
3.2. Test system facilities
1. The test facility shall include a sufficient number of rooms or premises to ensure separation of test systems and containment of projects using substances or organisms known to be or suspected to be biologically hazardous.
2. The test facility must have appropriate rooms or premises for the diagnosis, treatment and control of diseases, so that testing systems do not suffer an unacceptable degree of deterioration.
3. The test facility must have sufficient storage rooms or areas for supplies and equipment. Storage rooms or areas shall be separated from the rooms or premises hosting the test systems and sufficiently protected against infestation, contamination and/or deterioration.
3.3. Handling facilities
test and reference elements
1. To avoid contamination or mixtures, there must be separate rooms or premises for the reception and storage of test and reference elements and for the mixture of test elements with a vehicle.
2. The test elements storage rooms or areas shall be separated from the test rooms or premises. They must maintain identity, concentration, purity and stability and ensure safe storage of hazardous substances.
3.4. Archive rooms
Archive rooms must be provided for safe storage and consultation of study plans, raw data, final reports, samples, test and reference elements and specimens. Technical design and archiving conditions must protect the content from undue deterioration.
3.5. Waste disposal
Waste handling and disposal shall be carried out in such a way as not to jeopardize the integrity of the studies. This requires facilities to collect, store and evacuate waste in an appropriate manner, and define procedures for decontamination and transport.
4. Apparatus, materials and reagents
1. Devices, including validated computer systems, used for data collection, storage and consultation, and for the regulation of environmental factors involved in the study must occupy a correct location, be of appropriate design and have sufficient capacity.
2. Devices used in a study must be periodically inspected, cleaned, maintained and calibrated in accordance with standard operating procedures. A survey of these activities must be maintained. Calibration must be traceable to national stallions or to the international system of units (SI), if applicable, i.e. when the calibration exists and the measured parameter, such as mass, temperature or hygrometry, may be an influence factor on the quality of the result, if applicable, be reported to national or international metrology standards.
3. Devices and materials used in a study should not interfere with the test systems in any way.
4. Chemicals, reagents and solutions must be labelled and their nature (with concentration, if any), expiry date and special instructions for storage. Information on origin, preparation date and stability must be available. The expiry date may be extended on the basis of a documented assessment or analysis.
5. Test systems
5.1. Physics and Chemicals
1. Devices used to obtain chemical and physical data must occupy a correct location, be of appropriate design and have sufficient capacity.
2. The integrity of physical and chemical testing systems must be verified.
5.2. Biology
1. It is necessary to create and maintain appropriate conditions for the storage, housing, handling and maintenance of biological testing systems to ensure the quality of data.
2. Recently received animal and plant testing systems must be isolated until their health status has been assessed. If an abnormal mortality or morbidity is observed, the lot considered should not be used in the studies and be, if applicable, destroyed in accordance with the rules of humanity. At the beginning of the experimental phase of a study, the test systems must be free from any disease or symptom that could interfere with the purpose or conduct of the study. Test subjects that fall ill or are injured during a study must be isolated and treated, if necessary, to preserve the integrity of the study. Any diagnosis and treatment of any disease, before or during a study, must be documented.
3. Records must be maintained indicating the origin, date of arrival and the state upon arrival of the test systems.
4. Biological test systems must be acclimatized to the test environment for a sufficient period before the first administration or application of the test or reference element.
5. All information necessary for proper identification of test systems must be included on their accommodation or container. Each test system that may be extracted from the accommodation or container during the course of the study must bear appropriate identification marks to the extent possible.
6. During use, the units or containers of the test systems shall be cleaned and disinfected at appropriate intervals. Any material coming into contact with a test system shall not contain contaminants at concentrations that interfere with the study. The litter of the animals must be changed according to the requirements of good farming practices. The use of pest control agents must be explicit.
7. Test systems used in field studies should be arranged to prevent the dispersal of spand products and the prior use of pesticides from interfering with the study.
6. Test and reference elements
6.1. Reception, handling, sampling and storage
1. Records must be maintained indicating the characterization of the test and reference elements, the date of receipt, expiry date and quantities received and used in the studies.
2. Handling, sampling and storage methods must be defined that ensure the maintenance of homogeneity and stability to the extent possible and avoid contamination or mixture.
3. Storage containers shall be marked with identification information, expiry date and specific storage instructions.
6.2. Characterization
1. Any test and reference element must be appropriately identified (code, Chemical Abstracts Service Registration Number, name, biological parameters, for example).
2. For each study, the exact nature of the test or reference elements, including the lot number, purity, composition, concentrations or other characteristics that allow each lot to be defined in an appropriate manner.
3. When the test element is provided by the order donor, there must be a mechanism, defined in cooperation by the order donor and the test facility, which allows to verify the identity of the test element submitted to the study.
4. For all studies, the stability of test and reference elements must be known in storage and testing conditions.
5. If the test element is administered or applied in a vehicle, the homogeneity, concentration and stability of the test element must be determined in that vehicle. For test elements used in field studies (e.g. tank mixes) this information can be obtained through separate laboratory experiments.
6. A sample of each batch of the test element will be retained for analysis for all studies, with the exception of short-term studies.
7. Standard operating procedures
1. A test facility shall have written standard operating procedures approved by the facility management, which shall ensure the quality and integrity of the data obtained by the facility. Revisions to standard operating modes must be approved by the direction of the test facility.
2. Each section or area distinct from the test facility must have immediate access to the standard operating procedures for the work carried out there. Published works, methods of analysis, articles and manuals can be used as supplements to standard operating modes.
3. Deviations in relation to standard operating procedures for the study must be supported by documents and recognized as applicable by the study director, as well as by the main test officer(s) where applicable.
4. Standard operating modes must be available for the following categories of testing facility activities, the list of which is not limited. The specific tasks mentioned under each section below must be considered as examples.
1. Test and reference elements:
Reception, identification, labelling, handling, sampling and storage.
2. Devices, materials and reagents:
(a) Apparatus:
Use, maintenance, cleaning and calibration.
(b) Computer systems:
Validation, operation, maintenance, security, modification control and backup.
(c) Materials, reagents and solutions:
Preparation and labelling.
3. Data registration, reporting, storage and data consultation Data collection, data collection, reporting, indexing systems, data exploitation, including the use of computerized systems.
4. Test system (when applicable):
(a) Preparing the local and ambient conditions for the test system;
(b) Methods of receiving, transfer, correct implementation, characterization, identification and maintenance of the test system;
(c) Preparation of the test system, observations and examinations before, during and at the conclusion of the study;
(d) Handling of individuals belonging to the test system that are found to be dying or dead during the study;
(e) Collection, identification and manipulation of specimens, including autopsy and histopathology;
(f) Installation and provision of test systems on experimental plots;
(g) Waste disposal methods.
5. Quality assurance mechanisms.
6. Allocation of quality assurance personnel to planning, timing, completion, explanation and notification of inspections.
8. Realization of the study
8.1. Study Plan
1. For each study, a written plan should be established before the start of the work. The study plan must be approved by the Director of the study, who the date and the sign, and its compliance with the LPG must be verified by quality assurance personnel as indicated in paragraph 2.2 (b) above. This plan must also be approved by the direction of the test facility and the order donor if the regulation or legislation of the country where the study is carried out is required.
2. (a) Amendments to the study plan must be justified and approved by the study director, who dates and signs them, and then retained with the study plan;
(b) The deviations from the study plan must be described, explained, reported and dated in due course by the study director and by the main test managers and then retained with the raw data of the study.
3. For short-term studies, a general study plan can be used with a specific complement to the study.
8.2. Content of the study plan
The study plan must include the following information, which is not limited to:
1. Identification of the study, test element and reference element:
(a) A descriptive title;
(b) A presentation detailing the nature and object of the study;
(c) Identification of the test element by a code or name (IUPAC, CAS number, biological parameters, etc.);
(d) The reference element to be used.
2. Information on the order donor and the test facility:
(a) The name and address of the order donor;
(b) The name and address of any test facility and any relevant test site;
(c) The name and address of the study director;
(d) The name and address of the principal conductor(s) of the tests, and the phase(s) of the study delegated by the Director of the study to the principal conductor(s).
3. Dates:
(a) The date of approval of the study plan by affixing the signature of the study director. The date of approval of the study plan by affixing the signature of the direction of the test facility and the order donor if the regulation or legislation of the country where the study is carried out imposes it;
(b) The proposed dates for the beginning and end of experimentation.
4. Test methods:
The OECD Guidelines for Testing or another guideline or method to be used.
5. Special points (when applicable):
(a) The justification for the choice of the test system;
(b) The characterization of the test system, that is, the species, race, variety, origin, number of individuals, weight range, sex, age and other relevant information;
(c) The method of administration and the reasons for its choice;
(d) dose rates and/or concentrations, as well as frequency and duration of administration or application;
(e) Detailed information on the design of the experiment, which includes a description of the chronological conduct of the study, all materials, methods and conditions, the nature and frequency of the analyses, the measurements, observations and examinations to be performed, and statistical methods to be used (if applicable).
6. Records and records:
The list of records and records that must be kept.
8.3. Realization of the study
1. Each study must be given a specific identification. All elements relating to a particular study must bear this identification. The specimens of the study must be identified to confirm their origin. This identification must allow traceability, as necessary, of the specimen and study.
2. The study must be conducted in accordance with the agreed plan.
3. All data obtained during the course of the study must be recorded directly, quickly, accurately and legibly by the person reporting them. Data records must be signed or marked and dated.
4. Any modification of the raw data shall be recorded so as not to hide the previous mention; the reason for the change should be indicated with the date, signature or paraphrase of the person making the change.
5. The data obtained directly in the form of computer input must be identified as such when the data is introduced by the person(s) responsible for direct entry. The design of the computer system must always allow for the retention of all back-to-back checks to show all changes to the data without concealing the initial mention. It must be possible to associate all the changes made to the data with the persons who have made it through, for example, electronic signatures indicating the date and time. The reasons for the amendments will be mentioned.
9. Preparation of the report on the results of the study
9.1. General
1. A final report must be prepared for each study. For short-term studies, a standardized final report may be prepared and accompanied by a specific supplement to the study.
2. Principal test officers or scientists involved in the study must sign and date their reports.
3. The study director must sign and date the final report to indicate that he is responsible for the validity of the data. The degree of compliance with these principles of good laboratory practices must be indicated.
4. Corrections and additions to a final report must be in the form of amendments. These amendments must clearly specify the reason for corrections or additions and be signed and dated by the study director.
5. The preparation of the final report to comply with the terms and conditions of submission imposed by a national regulatory authority or the authority responsible for the approval is not a correction, addition or amendment to that final report.
9.2. Contents of the final report
The final report should provide the following information, but not limited to:
1. Identification of the study and test and reference elements:
(a) A descriptive title;
(b) Identification of the test element by a code or name (IUPAC, CAS number, biological parameters, etc.);
(c) Identification of the reference element by a name;
(d) The characterization of the test element, including its purity, stability and homogeneity.
2. Information on the order donor and the test facility:
(a) The name and address of the order donor;
(b) The name and address of each facility and test site concerned;
(c) The name and address of the study director;
(d) The name and address of the principal test officer(s) and the phases of the study delegated to them, if any;
(e) The name and address of scientists who provided records for the final report.
3. Dates:
Start and completion dates of experimentation.
4. Declaration:
A statement on the quality assurance program listing the types of inspections carried out and their dates, including the phase(s) inspected, as well as the dates on which each of the results of the inspections were communicated to the management and director of the study, as well as to the main test managers, if any. This statement will also confirm that the final report reflects the raw data.
5. Description of materials and test methods:
(a) A description of the methods and materials used;
(b) The OECD Guidelines for Testing, or another guideline or method.
6. Results:
(a) A summary of the results;
(b) All information and data requested by the study plan;
(c) A presentation of the results, including calculations and determinations of statistical interest;
(d) An assessment and review of results and, where appropriate, conclusions.
7. Storage:
The place where the study plan, the samples of the test and reference elements, specimens, raw data, and the final report shall be retained.
10. Storage and preservation of archives and materials
10.1. Will be kept in the archives for the ten-year period:
(a) The study plan, raw data, samples of test and reference elements, specimens and the final report of each study;
(b) Reports on all inspections conducted in accordance with the quality assurance program, as well as the master plans;
(c) Staff qualifications, training, experience and job descriptions;
(d) Records and reports relating to the maintenance and calibration of equipment;
(e) Documents relating to the validation of computer systems;
(f) The chronological record of all standard operating modes;
(g) Environmental monitoring reports.
When samples of test and reference elements and specimens are eliminated before the expiry of the required retention period for any reason, this removal must be justified and supported by documents. Samples of the test and reference elements and specimens shall be retained only as long as the quality of the preparation permits the evaluation.
10.2. Material retained in archives will be indexed to facilitate the storage and methodical consultation.
10.3. Only staff authorized by management will have access to the archives. Any entry and exit of archived material must be properly documented.
10.4. If a test facility or archival repository ceases to operate and does not have a legal successor, the archives must be handed over to the order donor(s) of the study(s).
Done in Paris, December 4, 2006.
Dominique de Villepin
By the Prime Minister:
Minister Delegate to Industry,
François Loos
The Minister of Employment,
social cohesion and housing,
Jean-Louis Borloo
Minister of Economy,
finance and industry,
Thierry Breton
Minister of National Education,
higher education
and research,
Gilles de Robien
Minister of Health and Solidarity,
Xavier Bertrand
Minister of Agriculture and Fisheries,
Dominic Bussereau
Minister of Ecology
and Sustainable Development
Nelly Olin
Minister for Employment, at Work
and the professional integration of young people,
Gérard Larcher
Minister Delegate
higher education
and research,
François Goulard
