The Royal Decree 822/1993 of 28 May, establishing the principles of good laboratory practice and its application in the conduct of non-clinical studies on chemicals, incorporated our Council Directive 87 /18/EEC of 18 December 1986 laying down the measures necessary to ensure that laboratories carrying out tests on chemical products are carried out in accordance with the provisions of the Directive 67 /548/EEC, comply with the principles of good laboratory practice specified in its Annex.

The Commission Directive 99 /11/EC of 8 March has amended Directive 87 /18/EEC, adapting to technical progress the principles of good laboratory practice in accordance with the Decision of the Council of the European Cooperation and Economic Development (OECD).

As a consequence of the previous adaptation, this Royal Decree comes to replace the Annex of Royal Decree 822/1993 of 28 May, incorporating into our legal order Directive 99 /11/EC.

In its virtue, on a proposal from the Ministers for Health and Consumer Affairs, Agriculture, Fisheries and Food and Science and Technology and after the report of the Inter-Ministerial Committee for Food Management, in agreement with the Council of the State and after deliberation by the Council of Ministers at its meeting on 14 July 2000,

D I S P O N G O:

Single item. Adaptation to technical progress of the principles of good laboratory practice.

1. The Annex to Royal Decree 822/1993 of 28 May 1993 is replaced by the Annex set out in this Royal Decree.

2. The content of the single final provision of Royal Decree 822/1993 of 28 May 1993 shall be replaced by the following:

" The Ministers for Health and Consumer Affairs, Agriculture, Fisheries and Food and Science and Technology are empowered to dictate the rules necessary for the implementation and development of the provisions in the field of their competences. in this Royal Decree, as well as for the updating of its Annex as a result of the timely modification of the Community rules. "

Final disposition first. Regulatory enablement.

This Royal Decree is of a basic rule, being dictated by the provisions of Article 149.1.16.a and 23.a of the Spanish Constitution.

Final disposition second. Entry into force.

This Royal Decree shall enter into force on the day following that of its publication in the "Official Gazette of the State".

Given in Madrid on July 19, 2000.

JOHN CARLOS R.

First Deputy Prime Minister and Minister of the Presidency, MARIANO RAJOY BREY

ANNEX

Principles of good laboratory practice (BPL)

SECTION I. INTRODUCTION

The quality of non-clinical health and environmental safety studies on which risk assessments are based is an issue that is deeply in the interest of both the state and industry. For this reason, the OECD member countries laid down criteria for the conduct of such studies.

In order to prevent the diversification of application programmes that could hinder international trade in chemical substances, OECD member countries have sought to achieve international harmonisation of chemical substances. testing and good laboratory practice. In 1979 and 1980, an international group of experts, established under the special programme on the control of chemical substances, drew up the so-called "OECD Principles of Good Laboratory Practice" (GLP), based on practices and practices. common management and scientific experience of various national and international sources. The OECD Council adopted these principles of GLP in 1981 as an annex to the Council Decision on the mutual acceptance of data on the assessment of chemical substances [C (81) 30 (final)].

In 1995 and 1996 a new group of experts was formed to review and update the principles. The current document is the result of the consensus reached by this group and annuls and replaces the original principles adopted in 1981.

The principles of good laboratory practice are intended to promote the quality of data from studies. The comparison of the quality of these data is the basis for their mutual acceptance between countries.

If each country can rely on data from studies developed in other countries, it is possible to avoid duplication of studies, thereby saving time and resources. The implementation of these principles should help to avoid the emergence of technical barriers to trade and to continue to improve the protection of human health and the environment.

1. Scope of application

The principles of good laboratory practice should be applied to non-clinical safety tests on test products contained in pharmaceutical products, pesticides, cosmetics, veterinary medicinal products, additives used in human and animal feed, and industrial chemicals. These test products are usually synthetic chemicals, but they may also be of natural or biological origin and, in some circumstances, may be live organisms. The purpose of the studies with these products is to obtain data on their properties and their safety for human health and the environment.

Non-clinical health and environmental safety studies covered by the principles of good laboratory practice include the work done in laboratories and greenhouses and field work.

Without prejudice to Article 3 of this Royal Decree, the principles of good laboratory practice shall apply, except for specific regulatory exemption, to all non-clinical health safety studies and (a) the environmental protection of the environment, the environment and the environment, the environment and the environment, the environment and the environment, and the environment. Regulation of industrial chemicals.

2. Definition of terms

1. Good laboratory practice (GLP).

Quality system related to organizational processes and conditions under which non-clinical health and environmental safety studies are planned, performed, controlled, recorded, archived, and informed.

2. Terms concerning the organization of the laboratory.

Laboratory: set of persons, premises and operational units required for the conduct of non-clinical health and environmental safety studies. In case of multicenter studies (those that are performed in more than one center), the laboratory understands the place where the Director of the Study is located and each and every one of the test centers that individually or collectively can be considered laboratories.

Test centre: site or sites where one or more phases of a study are carried out.

Laboratory address: person or persons with the authority and the formal responsibility for the laboratory to be organized and operate in accordance with the principles of good laboratory practice.

Test Center Address (if named):

person or persons responsible for ensuring that the phase or phases of the study under their responsibility are carried out in accordance with the principles of good laboratory practice.

Promoter: entity that commissions, finances and/or presents a non-clinical health or environmental safety study.

Director of the Study: person responsible for the overall performance of the non-clinical study on health or environmental safety.

Principal Investigator: a person who, in the case of multicenter studies, acts on behalf of the Director of the Study and has defined responsibilities for the phases of the study that have been delegated to him. The responsibility of the Director of the Study of the overall conduct of the study cannot be delegated to the Principal Investigator; the approval of the protocol and its modifications, the approval of the final report, and the assurance that they are followed by the principles of good laboratory practice.

Quality Assurance Program: a defined system, including personnel, which is independent of the conduct of the studies and is designed to assure the Laboratory Management of compliance with the principles of good laboratory practice.

Normalized work procedures (PNT):

documented procedures that describe how to perform trials or activities normally not detailed in the protocols or guidelines.

List of scheduled studies: gathering information to assist in the evaluation of the workload and for the follow-up of studies in the laboratory.

3. Terms for non-clinical health and environmental safety studies.

Non-clinical health and environmental safety study, hereinafter referred to simply as "study": experiment or set of experiments in which the test product is examined under the conditions of the laboratory or the environment, in order to obtain data from its properties and/or its security, intended for presentation to the competent regulatory authorities.

Short-term study: study with a short term of execution and performed with commonly used routine techniques.

Protocol: the document in which the objectives and the experimental design for the study are defined, including their possible modifications.

Modification to the protocol: intentional change in protocol after the date of the start of the protocol.

Protocol Deviation: Non-intentional change of protocol after the date of initiation of the protocol.

Experimental system: any biological, chemical, physical or combination system used in a study.

Primary data: original records and documentation of the laboratory or certified copies thereof, which are the result of the original observations and activities in a study. Primary data may also include, for example, photographs, microfilm or microfiche copies, computer readable data, rendered observations, data recorded by automated instruments, or any other means of storage data recognised as being capable of safely storing information during the period specified in Section II (10) of this Annex.

Specimen: any material derived from the experimental system for examination, analysis or storage.

The start date of the experimental phase: date when the first data specific to a study is collected.

End date of the experimental phase: Last date when data is collected from a study.

Study Start Date: The date when the Study Director signs the protocol.

Study Completion Date: The date the final report is signed by the Director of the Study.

4. Terms concerning the test product.

Test product: the object of a study.

Reference product ("control product"):

element used to provide a basis for comparison with the test product.

Lot: a specific quantity of a test or reference product produced during the same manufacturing cycle in such a way that it can be expected to be uniform and to be designated as such.

Vehicle: any carrier agent used for mixing, dispersing or solubilizing the test or reference product in order to facilitate administration or application to the experimental system.

SECTION II. PRINCIPLES OF GOOD LABORATORY PRACTICE

1. Laboratory organisation and personnel

1. Responsibilities of the Laboratory Directorate.

A) The Management of each laboratory must ensure that the principles of good laboratory practice are complied with.

B) The responsibilities of the Management include the following functions, not necessarily limited to them:

a) Ensure that there is a statement that identifies the individual or individuals in the laboratory who exercise the responsibility of Director, as defined in these principles of good laboratory practice.

b) Ensure the availability of sufficient qualified personnel, appropriate premises, equipment and materials for the timely and appropriate conduct of the study.

c) Ensure the maintenance of a record of qualifications, training, experience and description of the individual job position for each professional and technician.

(d) Ensure that the staff clearly understands the tasks to be carried out and, where necessary, provide the necessary training for the exercise of the duties.

e) Ensuring that appropriate and technically valid standard working procedures are established and followed; by approving all standard working procedures, both original and revised.

f) Ensure that there is a quality assurance program with the corresponding assigned personnel and ensure that the quality assurance responsibility is exercised in accordance with the principles of good laboratory practice.

g) Ensure that, prior to the start of each study, the Director of the Laboratory appoints a Director of Study with appropriate qualifications, training and experience.

The replacement of a Director of Study should be done in accordance with established procedures, and documented in an appropriate manner.

h) Ensure that in case of multicenter studies, if necessary, a principal investigator is appointed with appropriate qualifications, training and experience to monitor the phase or phases of the delegated study. The replacement of a principal investigator should be done in accordance with established procedures, and properly documented.

i) Ensure that the Director of the Study approves the protocol in writing.

j) Ensure that the Director of the Study has placed the approved protocol at the disposal of the quality assurance staff.

k) Ensure the maintenance of a historical archive of all standard working procedures.

l) Ensure that a manager is named for the management of the file.

m) Ensure that the list of scheduled studies is maintained.

n) Ensure that laboratory supplies meet the appropriate requirements for use in a study.

n) Ensure that, in multicenter studies, there are clear lines of communication between the Director of the Study, the lead researcher, the quality assurance program, and the study staff.

o) Ensure that the test and reference products are properly characterized.

p) Establish procedures to ensure that computerised systems are suitable for the intended purpose and are validated, used and maintained in accordance with the principles of good laboratory practice.

C) When one or more phases of a study are carried out in a test centre, the responsibilities defined in the previous point shall correspond to the test centre address (if designated) with the following exceptions: (a), (b), (g), (i), (j) and (n).

2. Responsibilities of the Director of the Study.

A) The Director of the Study is the one who centralizes the control of the study and to him corresponds the overall responsibility of the realization of the study and of its final report.

B) The responsibilities of the Director of the Study include the following functions, not necessarily limited to them:

a) Approve the study protocol and any modifications made to it, by signing it and dating it.

(b) Ensure that quality assurance personnel have at the time of a copy of the protocol and of any modification produced, maintaining during the conduct of the study an effective communication with the guarantee staff quality according to the needs.

c) Ensure that the protocol, modifications and standard procedures of work are available to study staff.

d) Ensure, in a multicenter study, that the protocol and final report identify and define the role of each principal investigator, laboratory, and trial center participating in the study.

e) Ensure that the procedures specified in the protocol are followed; assess and document the impact of the protocol deviations on the quality and integrity of the study, taking, if necessary, the (a) the necessary corrective measures to be taken, and to allow deviations to be made during the conduct of the study in respect of the standard working procedures.

f) Ensure that all generated primary data is fully documented and recorded.

g) Ensure that the computerised systems used in the study have been validated.

h) Sign and date the final report, accepting responsibility for the validity of the data and point out to what extent the study complies with the principles of good laboratory practice.

i) Ensure that after the completion of the study (even in case of interruption) they are archived: the protocol, the final report, the primary data and the support material.

3. Principal investigator's responsibilities.

The principal investigator will ensure that the delegated study phases are carried out in accordance with the principles of good laboratory practice that are applicable.

4. Responsibilities of study staff.

A) All personnel involved in the conduct of the study should be aware of those parts of the principles of good laboratory practice applicable to their participation in the study.

B) The study staff should have access to the protocol and the corresponding standard working procedures applicable to their participation in the study. The study staff will be responsible for complying with the instructions given in these documents. Any deviation from these instructions should be documented and communicated directly to the Director of the Study and, if appropriate, to the principal investigator.

C) The study staff will be responsible for recording the primary data quickly and accurately and in accordance with the principles of good laboratory practice; it will also be responsible for the quality of the data.

D) Study staff should take appropriate health precautions to minimize the risks to their health and ensure the integrity of the study. In addition, the staff of the study must inform the appropriate person of any relevant illness or medical alteration, so that they may be excluded from the operations which might affect the study.

2. Quality assurance program

1. General.

A) The laboratory must have a documented quality assurance program in order to ensure that the studies carried out comply with the principles of good laboratory practice.

B) The quality assurance program must be carried out by a person or persons appointed by the Directorate and directly responsible to it, and they will be familiar with the work procedures.

C) The person or persons responsible for the quality assurance program may not be involved in the conduct of the study to be assured.

2. Responsibilities of the quality assurance staff.

The responsibilities of quality assurance personnel include the following functions, not necessarily limited to them:

a) Keep a copy of all approved protocols and standard procedures of work approved and in use in the laboratory, and have access to an updated copy of the list of scheduled studies.

b) Verify that the study protocol contains the information necessary to comply with the principles of good laboratory practice. This verification must be recorded in writing.

c) Carry out inspections to determine whether all studies are carried out in accordance with the principles of good laboratory practice and that the standard working protocols and procedures have been made available of the study staff and are followed.

Inspections can be of three types as provided for in standard quality assurance program work procedures:

1.o Studies based on studies, 2.o facility-based Inspections, 3.o Process-based Inspections.

Records of the inspections carried out must be kept.

d) Audit the final reports to verify that the methods, procedures and observations are accurate and fully described and that the results of the report accurately and completely reflect the primary data of the studies.

e) promptly inform in writing of the results of each inspection to the Laboratory Directorate and the Director of the Study, as well as, where appropriate, the principal investigator or investigators and their respective Directorates of the center.

f) Develop and sign a declaration, to be included in the final report, specifying the types of inspections carried out and their dates, including the phase or phases of the survey inspected, and the dates on which the the results of the inspections were reported to the Directorate, to the Director of the Study and, where appropriate, to the principal investigator. This statement should also serve to confirm that the final report accurately reflects the primary data.

3. Installations

1. General.

A) The facilities must meet the appropriate size, construction and location conditions to meet the requirements of the study and minimize any changes that may interfere with the validity of the study. study.

B) The design of the facilities should allow for adequate separation between the different activities, in order to ensure the correct performance of each study.

2. Installations of the experimental system.

A) The laboratory must have a sufficient number of rooms or areas to ensure the isolation of experimental systems and/or individual projects in which substances or organisms known to be used are used. Suspect that they may behave biological hazards.

B) The appropriate rooms or areas for diagnosis, treatment and disease control should be available to ensure that the experimental systems do not suffer an unacceptable degree of deterioration.

C) The laboratory must have rooms or storage areas suitable for supplies and equipment. The rooms or storage areas must be separated from the rooms or areas where the experimental systems are housed, and must provide adequate protection against infestation, contamination and/or deterioration.

3. Facilities for the handling of test and reference products.

A) To prevent contamination or mixtures, separate rooms or areas shall exist for the reception and storage of test and reference products and for the mixing of test products with a vehicle.

B) The rooms or storage areas for the test products shall be separated from the rooms or areas in which the experimental systems are located. They shall meet the appropriate conditions for the preservation of identity, concentration, purity and stability and ensure safe storage of dangerous substances.

4. File rooms.

You must have file facilities to securely store and retrieve protocols, primary data, final reports, samples of test products, and specimens. The file design and file conditions must be adequate to protect your content against accelerated or premature deterioration.

5. Waste disposal.

The handling and disposal of waste must be carried out in a way that does not endanger the integrity of the studies and in accordance with the provisions of Law 10/1998 of 21 April of Waste.

This implies the existence of adequate facilities for the collection, storage and disposal of waste, as well as for decontamination and transport procedures.

4. Apparatus, materials and reagents

1. Apparatus, including validated computerised systems, used for the collection, storage and retrieval of data, and for the control of environmental factors relevant to the study, shall be properly located and counted with the appropriate design and capacity.

2. The apparatus used in a study shall be examined, cleaned, maintained and calibrated periodically, following standard working procedures. Each of these activities shall be duly registered. The calibration shall, where appropriate, be traceable to national or international measurement patterns.

3. The apparatus and materials used in a study should not interfere negatively with the experimental systems.

4. Chemical substances, reagents and solutions must be labelled indicating the identity (pointing out, if appropriate, their concentration), the expiry date and the specific storage conditions.

The information regarding the source, date of preparation and stability should be available. The expiry date may be extended by duly documented assessment or analysis.

5. Experimental systems

1. Physical and chemical systems.

A) The apparatus used for the production of physical or chemical data shall be properly situated and shall have the appropriate design and capacity.

B) The integrity of the physical and chemical experimental systems must be guaranteed.

2. Biological systems.

A) In order to ensure the quality of data, appropriate conditions for storage, accommodation, handling and care of biological experimental systems should be established and maintained.

B) Animal and plant experimental systems shall be isolated immediately after receipt, until their health status has been evaluated. If abnormal mortality or morbidity occurred, the lot in question should not be used in any study and should be destroyed in a humanitarian way at the time. At the start date of the experimental phase of a study, the experimental systems should be free of any disease or disorder that could affect the objective or the performance of the study. Experimental systems that fall ill or become damaged in the course of a study should be isolated and, if necessary, treated in order to maintain the integrity of the study. Any diagnosis and treatment of a disease occurring before or in the course of a study must be recorded.

C) Records of provenance, date and conditions of arrival of the experimental systems must be maintained.

D) Before the first administration or application of the test or reference product, the biological experimental systems shall be acclimated to the test environment for an appropriate period.

E) The enclosures and containers of the experimental systems must be correctly identified. In cases where it is possible, the individual experimental systems to be removed from their housing or container during the conduct of the study shall be appropriately identified.

F) During their period of use, the enclosures and containers of the experimental systems shall be cleaned and disinfected at appropriate intervals.

All material that comes into contact with the experimental system should be free of any level of contaminants that could affect the study. Animal beds must be changed as required for the good practice of the use, handling and rearing of animals. The use of antiparasitic agents should be documented.

G) The experimental systems used in field studies should be located in such a way as to prevent the study from being affected by erratic aerosols and the prior use of pesticides.

6. Test and reference products

1. Reception, handling, sampling and storage.

A) Records shall be maintained including the characterization of the test and reference products, date of receipt, date of expiry, and quantities received and used in the studies.

B) Procedures for handling, sampling and storage should be established in order to ensure the greatest possible degree of homogeneity and stability, and to avoid contamination or mixing.

C) The storage containers must bear the identification data, the expiry date and the specific storage instructions.

2. Characterization.

A) All test and reference products shall be duly identified [example: by code, Chemical Abstracts Service number, name and biological parameters].

B) In each study, the identity, including the batch number, purity, composition, concentrations and other characteristics necessary to define each batch of test or reference product, shall be known.

C) In cases where the test product is supplied by the sponsor, there shall be a mechanism developed in collaboration between the promoter and the laboratory to verify the identity of the test product under test. study.

D) The stability of test and reference products under storage and testing conditions shall be known in all studies.

E) If the test product is administered or applied in a vehicle, the homogeneity, concentration and stability of the test product in that vehicle shall be determined. In the case of test products used in field studies (e.g. tank mixtures), these values can be determined by different laboratory experiments.

F) In all studies, except for short-term studies, a sample shall be kept for analytical purposes for each batch of test product.

7. Standard procedures for work

1. Every laboratory must have standard procedures of work written and approved by the Laboratory Directorate, aimed at ensuring the quality and integrity of the data obtained by the laboratory. Reviews of the standard working procedures shall be approved by the Directorate of the Laboratory.

2. Any unit or area separate from the laboratory shall immediately have available standard working procedures related to the activities carried out on them. Published textbooks, analytical methods, articles and manuals may be used as supplements to these standard working procedures.

3. Deviations from the standard working procedures related to the study shall be documented and supported by the Director of the Study and, where appropriate, the principal investigator.

4. Standard working procedures should be available for the following categories of laboratory activities, not limited to them (the concepts under each heading should be considered illustrative examples):

A) Test and reference products: reception, identification, labelling, handling, sampling and storage.

B) Appliances, materials and reagents:

a) Appliances: use, maintenance, cleaning and calibration.

b) computerised systems: validation, operation, maintenance, security, change control and backup.

c) Materials, reagents and solutions: preparation and labelling.

C) Maintenance of records, reports, storage and recovery: coding of studies, data collection, preparation of reports, indexing systems, data processing, including the use of computerised systems.

D) Experimental systems (where applicable):

a) Preparation of the room and its environmental conditions for the experimental system.

b) Procedures for reception, transfer, correct location, characterization, identification and care of the experimental system.

c) Preparation, observations and examinations of the experimental system, before, during and at the conclusion of the study.

d) Manipulation of individuals from an experimental system found to be dying or dying during the study.

e) Collection, identification and manipulation of specimens, including autopsy and histopathology.

f) Situation and placement of experimental systems in test plots.

E) Quality assurance procedures: performance of quality assurance personnel in the planning, programming, implementation, documentation and drafting of audit reports.

8. Conduct of the study

1. Protocol.

A) Each study must have a written protocol prior to its initiation. The protocol must be approved and dated by the Director of the Study. Quality assurance personnel shall verify that the protocol complies with the GLP as specified in paragraph 2 (B) (b) of Section II. The protocol must also be approved by the Laboratory Directorate and the promoter.

B) Modification and deviations from the protocol:

(a) The modifications to the protocol shall be justified and approved and dated by the Director of the Study, and shall be maintained at all times together with the protocol.

(b) The deviations of the protocol shall be described, justified, recognized and dated at the time by the Director of the Study and/or the principal investigator and maintained at all times together with the primary data of the study.

C) In the case of short-term studies, a general protocol may be used, accompanied by a specific supplement to the study in question.

2. Content of the protocol. The protocol shall contain, without limitation, the following information:

A) Identification of the study, the test product and the reference product:

a) A descriptive title.

b) Description about the nature and purpose of the study.

c) Identification of the test product by code or denomination (IUPAC; CAS number, biological parameters, etc.).

d) The name of the reference product to be used.

B) Information concerning the promoter and the laboratory:

a) Name and address of the promoter.

b) Name and address of all laboratories and test centres involved.

c) Name and address of the Director of the Study.

d) Name and address of the principal investigator or principal investigators, and the phase or phases of the study delegated by the Director of the Study and subject to the responsibility of the principal investigator.

C) Dates:

(a) The date of the signing of the protocol by the Director of the Study and the date of the signing of the protocol by the Management of the Laboratory and the promoter.

b) The proposed start and end dates of the experimental phase.

D) Test methods: reference to OECD guides, other guides or methods to be used.

E) Other information, where appropriate:

a) Justification of the choice of the experimental system.

b) Characterization of the experimental system, indicating species, strain, substrain, origin, number, body weight range, gender, age, and other relevant data.

c) Method of administration and reasons for your choice.

d) Dose levels and/or concentration, frequency and duration of administration or application.

e) Detailed information on the experimental design, including a description of the chronological development of the study, of all methods, materials and conditions, type and frequency of analyses, measures, observations and examinations must be carried out and, if necessary, the statistical methods to be used.

F) Documents: A list of documents to be retained.

3. Conduct of the study.

A) Each study must be uniquely identified.

This identification should appear in all matters related to the study. Specimens of the study must be identified to confirm their origin. This identification shall permit appropriate traceability for each specimen and the study.

B) The study should be conducted in accordance with the protocol.

C) All data generated during the conduct of the study must be recorded immediately, directly, accurately and legibly by the persons responsible for the data recording. These records must be dated and signed with the initialling or initials of those responsible.

D) Any modification of the primary data shall be carried out in such a way as not to hinder the reading of the prior entry and indicating the reason for the change, and shall be dated and signed or marked with the initials of the person who makes the change.

E) Data obtained as direct computer inputs shall be identified in time and date of their introduction by the person responsible for their entry. Computerised systems should be designed to enable data retention to be carried out at all times in order to carry out retrospective audits that show all changes in data without hiding the original data. It should be possible to associate all data changes with the people who have made it, for example by electronic signatures with time and date. The amendments shall be justified in all cases.

9. Information from the results of the study

1. General.

A) A study will be completed, a final report must be produced. In the case of short-term studies, a standardised final report, supplemented by an annex specifically referred to in the study concerned, may be drawn up.

B) The reports of the main researchers or scientists involved in the study should be signed and dated by themselves.

C) The final report shall be signed and dated by the Director of the Study in order to indicate its acceptance of the responsibility for the validity of the data.

The extent to which the study complies with the principles of good laboratory practice should be mentioned.

D) Any correction or addition to a final report shall be made in the form of an amendment. The amendments shall clearly specify the reason for the corrections or additions and shall be signed and dated by the Director of the Study.

E) The change of format of the final report to comply with the requirements for the submission of a national register or a regulatory authority shall not constitute a correction, addition or amendment to the final report.

2. Content of the final report. The final report shall include, without limitation, the following information:

A) Identification of the study, the test product and the reference product:

a) A descriptive title.

b) Identification of the test product by code or denomination (IUPAC; CAS number, biological parameters, etc.).

c) The name of the reference product to be used.

d) Characterisation of the test product, including purity, stability and homogeneity.

B) Information concerning the promoter and the laboratory:

a) Name and address of the promoter.

b) Name and address of all participating laboratories and test centres.

c) Name and address of the Director of the Study.

d) Name and address of the principal investigator (s) and the phase (s) of the delegated study, if applicable.

e) Name and address of the scientists who have contributed reports to the final report.

C) Dates: the start and end dates of the experimental phase.

(D) Declaration: a declaration of the quality assurance programme listing the types of inspections carried out and the dates on which they took place, specifying the stage or phases examined, and the dates on which they were informed the results of the inspections to the Directorate, the Director of the Study and, where appropriate, the principal investigator. This statement will also serve to confirm that the final report accurately reflects the primary data.

E) Description of test materials and methods:

a) Description of the methods and materials used.

b) Reference to OECD guidelines, other guides or test methods.

F) Results:

a) A summary of the results.

b) All information and data required in the protocol.

c) An exposure of the results, including calculations and determinations with statistical significance.

d) An assessment and discussion of the results and, if appropriate, the conclusions reached.

G) File: the place where the protocol will be retained, samples of test and reference products, specimens, primary data and the final report.

10. Archive and preservation of records and materials

1. They must be kept in the archives for at least one year after the end of the marketing of the product:

(a) The protocol, primary data, samples of test and reference elements, specimens and the final report of each study.

b) Records of all inspections carried out by the staff of the quality assurance program, and the list of scheduled studies.

c) Records of qualifications, training, experience and job description of staff.

d) Records and reports of the maintenance and calibration of the devices.

e) Validation documents for computerised systems.

f) The historical file of the Normalized Labor Procedures.

g) Records of environmental controls.

In the case of non-marketing of the product, the above documentation shall be kept for as long as the laboratory considers appropriate, documenting the removal of all material from the study.

When samples of test and reference products or specimens are to be removed for any reason before the required retention period is due, it shall be duly justified and documented. Samples of test and reference products and specimens shall be kept only as long as the quality of the preparation permits the assessment.

2. The material retained in the archives must be indexed in order to facilitate proper storage and recovery.

3. Only the personnel authorized by the Directorate may have access to the files. The entries and outputs of material from the archives must be properly registered.

4. If a laboratory or a contract file ceases its activity and has no legal successor, the file must be transferred to the files of the promoter or the promoters of the studies.