Decree of the Ministry of Health and the Ministry of Agriculture No. 74 / 1998 Coll.
Decree of the Ministry of Health and the Ministry of Agriculture establishing good laboratory practice in the field of pharmaceuticals
Valid
Effective from 10.04.1998
74
DECLARATION
Ministry of Health and Ministry of Agriculture
of 27 March 1998
establishing good laboratory practice in the field of pharmaceuticals
The Ministry of Health and the Ministry of Agriculture, pursuant to § 75 (2) (c) of Act No. 79 / 1997 Coll., on Medicines and on amendments and additions to certain related laws, provides:
Preliminary provisions
This Decree sets out a set of rules for the planning, implementation, control, evaluation and documentation of laboratory tests in the framework of pre-clinical testing and clinical trial of medicinal products in order to ensure the quality, accuracy and completeness of the data obtained ("good laboratory practice ') .1.
For the purposes of this decree:
1. testing equipment of the workplace where laboratory tests are carried out;
2. laboratory testing or laboratory test set (hereinafter referred to as "laboratory tests") procedures for testing the test material according to good laboratory practice;
3. the test substance or mixture of substances subject to laboratory testing;
4. the contracting authority of the laboratory tests, the natural or legal person for which the laboratory tests are carried out under contract;
5. a study of the laboratory test according to the contract award;
6. a biological, chemical or physical test system used in laboratory tests or combinations thereof, as appropriate;
7. primary data, all records and documentation obtained as a result of observations and activities during laboratory tests, including their photographs, microfilms, microlabels, records on electronic media, dictated observations, records from automatic instruments or records on any other media storing information safely;
8. Sample of the testing system any material which is part of the testing system and is taken for testing, evaluation or preservation, including material taken from the assessed subjects in carrying out the clinical trial;
9. reference material the substance or mixture of substances used to compare with the test material;
10. carrier medium a substance or mixture of substances defined by properties with which the test or reference material is mixed or dissolved or dispersed in order to permit testing in the test system.
ADMINISTRATIVE LABORATORY PRACTICE
Principles
(1) Where laboratory testing operators in the framework of pre-clinical testing or clinical trial of medicinal products, (2) as well as persons involved in carrying out such tests follow the OECD Principles of Good Laboratory Practice, (3) to be published in the Ministry of Health Bulletin, the procedure shall be considered to be in line with the provision of good laboratory practice under this Decree.
(2) All animal testing shall be carried out in the testing facility in accordance with the specific regulation.4)
(3) All information on laboratory tests and other activities related to laboratory tests shall be recorded, processed and documented so that they can be reconstructed at any time.
(4) In order to ensure the necessary quality of laboratory tests,
(a) all persons involved in laboratory tests are familiar with the organisational and operational rules of the testing facility and with their work assignment and with the tasks of carrying out laboratory tests;
(b) for each study prior to its initiation, its leader and for the separate parts of the study leading to the partial examination;
(c) the test and reference material (§ 12) is characterised,
(d) computer systems appropriately developed, used and maintained to match the intended purpose;
(e) established standard operating procedures (Section 8);
(f) the procedures and results of laboratory tests and, where appropriate, other activities related to laboratory tests (§ 13) have been checked.
Planning of laboratory tests
(1) The operator shall ensure the planning of laboratory tests, including the establishment of the organisational and operational arrangements of the testing equipment, the responsibilities and workload of the managers and other persons involved in laboratory tests, as well as standard operating procedures and studies.
(2) Laboratory tests shall follow the plan of each study which, when excluding foreseeable effects, determines the purpose of the study and defines the design of the experiment.
(3) The laboratory test plan (hereinafter referred to as the study plan) contains in particular:
(a) descriptive name and, where appropriate, study code;
(b) a statement characterising the nature and purpose of the study;
(c) identification of test and reference materials and identification of supporting media;
(d) the name and address of the contracting entity and of the testing facility;
(e) the name and address of the study leader and, where appropriate, of the partial examination managers, indicating the parts of the study for which they are responsible;
(f) the date of approval of the study plan with the signatures of the study manager and contracting entity;
(g) dates of experimental initiation and experimental termination of the study;
(h) justification for the selection of test systems;
(i) characteristics of test systems (species, strain, source of supply, number, extent of body weight, sex and other necessary information),
(j) methods and forms of application of test and reference materials to the test system, dose size, concentration, intervals, frequency and time of application, as well as their justification;
(k) a detailed description of the design of the study, including the size and number of test groups, the estimated time course of the study, listing all methods, materials and conditions, types and frequency of analyses, measurements, observations and examinations to be used, where appropriate recommendations on the use of statistical methods;
(l) a list of the documentation to be kept.
(4) Complements to the study plan shall be drawn up, justified and signed by the study manager and shall be kept together with the study plan.
(5) Derogations from the study plan shall be described, explained and validated in a timely manner by the study manager and dated. These records are kept together with the primary data of the study.
Carrying out laboratory tests
Study
(1) Laboratory trials of the study are initiated by signing the study plan and completed by signing the final study report. the signatures shall be accompanied by a date. Within this range, the moment when the first primary data are obtained is referred to as the experimental initiation of the study and the time when the study provides the last primary data, as the experimental termination of the study.
(2) The study leader shall be responsible for the overall conduct of laboratory tests, including the final report and complete documentation.
(3) Each study is clearly identified. During the study, all materials and documentation used shall be identified uniformly with the study name or code specified in the study plan.
(4) Except for short-term studies, control samples shall be kept from each batch of test and reference material. Samples of test systems taken shall be marked in such a way that their origin is obvious and traceable. The sampling, transport, storage and processing of samples of the test system shall be carried out under conditions which do not jeopardise the completeness of the study; these conditions shall be documented and validated.
(5) All data, data, measurement results and observations shall be recorded directly, without delay, accurately and legibly and shall be dated and signed by the authorised person; direct computer inputs must be recorded in this way when they are inserted into the computer. At
(a) any changes in the measurement data and results shall be justified and dated and signed by the person responsible for the change;
(b) any modification of the primary data shall be carried out in such a way that the original entry is not covered; the change shall be dated and signed by the person making the change, indicating the reason for the change.
(6) Computer systems shall be processed in such a way that any changes to the data made can be re-checked at any time.
Any person involved in the study
(a) they must maintain health measures to prevent or minimise their own damage;
(b) be responsible for the quality and prompt and accurate recording of primary data;
(c) they must be excluded from participation in the study if they could interfere with the course and results of the study.
Final study report
(1) Each study is completed by a final report. In the case of short-term studies, it is permissible to use the standardised final report for a specific type of study, supplemented by an addendum specifying a specific study.
(2) The final study report shall be dated and signed by the study manager. Any deviations from good laboratory practice that would occur during the study should be justified and their impact on the study indicated.
(3) The final study report shall include in particular:
(a) the descriptive name of the study and, where appropriate, the study code;
(b) identification of test and reference materials, including evaluation of their homogeneity and stability;
(c) identification of carrier media;
(d) the names and addresses of the contracting authority, the operator and the testing facility, as well as the places where the laboratory tests are carried out;
(e) the names and addresses of the study leader and, where appropriate, of the study director and of the persons who contributed by sub-reports to the final study report;
(f) dates of experimental initiation and experimental termination of the study;
(g) a statement by the person responsible for the quality group's activities (Section 13) of the results of the checks carried out, including an indication of the type of checks carried out and of any reports by the study leader and the testing facility, as well as details of the compliance of the final report with the primary data;
(h) a list and description of test methods including references to professional literature;
(i) all information and data required by the study plan;
(j) the results of the study, including the calculation and determination of statistical significance;
(k) evaluation of study results and conclusions;
(l) the place where the study plan, samples of test and reference materials, samples of test systems, primary data and final report are kept.
(4) Corrections and extensions of the final study report shall be made in the form of additions containing their justifications and bearing the date and signature of the study leader.
Standard operating procedures
(1) Standard operating procedures for testing equipment must guarantee the quality and completeness of the data obtained. Each part of the test equipment shall have a valid version of it relating to the activity it carries out for immediate use.
(2) Standard operating procedures apply in particular to the following activities:
(a) reception, identification, labelling, handling, sampling and storage of test and reference materials;
(b) the operation, maintenance, cleaning, adjustment and calibration of instruments;
(c) development, operation, maintenance, reliability, changes and backup of computer systems;
(d) preparation, marking, verification and storage of materials, agents and solutions;
(e) laboratory record keeping, data collection, study encoding, index systems, data manipulation including the use of computer systems;
(f) the preparation of premises and environmental conditions for test systems;
(g) procedures for reception, handling, proper positioning, characterisation and care of test systems;
(h) preparation, inspection and observation of test systems before, during and at the end of the study;
(i) handling of individuals of the biological testing system found to be in a state of inapplicable during the study;
(j) collection, identification and handling of samples of the testing system, including autopsy and histopathology;
(k) the location of test systems at the testing facility premises;
(l) quality group procedures for the planning, implementation, documentation and recording of checks;
(m) cleaning and sanitation of cages and containers intended for testing systems and the replacement of bedding for animals, including the determination of time intervals.
Test equipment spaces
The test equipment spaces shall meet the requirements of laboratory testing. At the same time,
(a) the isolation of the test systems and the isolation of the ongoing tests shall be ensured in the test system spaces, in particular where materials which are or could be biologically or otherwise dangerous are used;
(b) where biological testing systems are used, special areas shall be reserved for the diagnosis, treatment and control of diseases of living organisms;
(c) storage areas are reserved for supplies and equipment, separate from those in which testing systems are located and protected against destruction, pollution or deterioration of the quality of such supplies and equipment;
(d) for the reception and storage of test and reference materials, and for their measurement, mixing with carrier media and other processing, premises shall be reserved separate to ensure their identity, concentration, purity and stability and, in the case of hazardous substances, safe storage;
(e) for the safe storage of study plans, primary data, final reports and other documentation, samples of test and reference materials, samples of test systems and, where appropriate, other samples, the testing equipment shall be equipped with lockable spaces which are adapted to prevent the premature deterioration of the retained material;
(f) tests and studies on live animals may only be carried out in testing facilities which have been accredited. 5)
Instruments, materials and reagents
(1) Apparatus, including computer systems, used for the acquisition, storage and generation of data and for influencing or monitoring the environment related to studies shall comply with the laboratory tests carried out by their characteristics, design, capacity and location, be regularly checked, cleaned, maintained, adjusted and calibrated according to standard operating procedures. Such activities shall be kept in the records to be kept. The calibration shall ensure comparability with national or international measurement standards.
(2) Instruments and materials used in laboratory tests must not adversely affect test systems.
(3) The chemicals, reagents and solutions used in laboratory tests are identified by the name and, where appropriate, by the concentration, the expiry date and, if necessary, the need for special storage, including the storage method. Information on origin, date of preparation and stability shall be available. The period of application may be extended on the basis of documented testing or analysis.
Test systems
(1) Records of the source, date and conditions of delivery of test systems shall be kept. In the experimental initiation of the study, the test systems shall be free of any disease or condition that could adversely affect the target or course of the study.
(2) For the location and treatment of biological testing systems (animals, micro-organisms, cellular and subcellular materials) and for handling them, conditions must be introduced and maintained in order to guarantee the quality of the data obtained, followed by specific rules. 6)
(3) The newly obtained biological testing systems (animal and plant) are isolated until their health is established. If a disease or other damage occurs during the study, biological testing systems shall be isolated or treated to the extent necessary to maintain the reliability of the study; If mortality or disease secreting such treatment occurs, the biological testing system for the study cannot be used.
(4) All diagnoses and treatments of patients with biological testing systems prior to or during the study are reported.
(5) Biological test systems are based on test conditions long enough before the experimental start of the study; the period of treatment is specified in a separate Regulation (7).
(6) Biological testing systems must be clearly marked on individuals, cages or containers. Individual test systems which are removed from cages or containers are appropriately marked during the study.
(7) All material that comes into contact with test systems must not contain impurities in concentrations that could affect the study. The use of pest control devices shall be documented.
Test and reference materials
(1) The test materials and reference materials shall be recorded in writing indicating the name, origin, batch numbers, reception dates, period of application, the quantity accepted and the quantity used in the study; handling, sampling and storage shall be carried out in such a way as to avoid confusion and contamination of materials and to preserve their homogeneity and stability.
(2) Containers with tested and reference materials stored are identified by the name, the expiry date and the storage method.
(3) The test and reference material used in the study is identified and characterised by the following:
(a) name, including international chemical identification code or biological parameters;
(b) batch number, composition, purity, concentration or other particulars suitable for the characterisation of the lot (to be indicated for each test and reference material),
(c) stability of test and reference materials under storage conditions;
(d) stability of test materials and reference materials under test conditions.
(4) If the test or reference material is administered with the carrier medium, the homogeneity, concentration and stability of the material in the carrier medium shall be determined.
CONTROL AND EVALUATION OF LABORATORY TESTS AND STORAGE OF DOCUMENTATION AND SAMPLES
Control and evaluation
(1) A quality group shall be carried out in the testing facility to check and evaluate compliance with laboratory testing.
(2) The quality group shall follow its activity plan and document its activity. Persons working in the quality group may not participate in the laboratory tests they control.
(3) The quality group shall maintain all applicable standard operating procedures and study plans and shall carry out in particular the following tasks:
(a) check the study plans, in particular whether they contain all the information required;
(b) verify the competence of the study participants;
(c) carry out checks on all studies and on premises and procedures;
(d) verify that the study plans and the relevant standard operating procedures are available to and follow the study participants;
(e) check the final reports of the studies, in particular whether the methods, procedures and observations used are correctly and accurately stated in each report and are consistent with primary data;
(f) make a statement on the results and dates of the checks, the manner and dates of informing the head of the test facility and the study leader and that the final report is consistent with primary data; the declaration is attached to the final study report,
(g) checks compliance with the organisational and operational rules;
(h) check that the relevant managers are immediately informed of any findings, in particular any identified and undocumented deviations from the study plan and standard operating procedures.
(4) The head of the quality group shall confirm the results of the inspection tasks as well as the declarations and information referred to in the previous paragraph by signature and date.
Storage of documentation and samples
(1) They are stored
(a) plans for studies;
(b) primary data;
(c) final reports;
(d) records of the quality group of checks carried out in the testing establishment and the opinion of the head of the testing establishment and, where appropriate, of other persons on the deficiencies identified;
(e) documents and records of qualifications, training and experience of staff members and their job descriptions;
(f) maintenance, adjustment, repair and calibration records;
(g) any earlier and valid versions of standard operating procedures;
(h) samples of test and reference materials;
(i) samples of test systems;
(j) a list of the documentation and samples stored;
(k) documentation on the validation of computer systems;
(l) the organisational and operational arrangements of the testing facility.
(2) The documentation and samples stored are identified and stored in a way that allows easy tracing.
(3) Only persons authorised to do so shall have access to the documentation and samples stored; records shall be kept by the person responsible for entering and storing and removing the stored documentation and materials from those premises.
(4) Documentation, primary data and other written material shall be kept for at least 10 years after their deposit.
(5) Samples of test and reference materials shall be kept for the period of application; if this period is not indicated, they shall be kept for at least 10 years after their deposit.
(6) Samples of test systems shall be kept for at least 10 years from their storage, if their condition permits; otherwise the responsible person shall obtain a record of their earlier liquidation indicating the reason for the liquidation.
(7) In the event that the test equipment ceases to operate, the operator shall decide on the transmission of documentation and samples from the laboratory tests of the study to the acquiring installation and, failing that, to the competent contracting authority.
Final provisions
This decree shall take effect on the day of its publication.
Minister for Health:
Dr. Roith, MBA v. r.
Minister for Agriculture:
Ing. Lux v. r.
1) Paragraph 4 (7) of Act No. 79 / 1997 Coll., on Medicines and on the amendments and additions to certain related laws.
2) Articles 4 (1) (e), 3 (2) and 9 (1) (a) (5) of Act No. 79 / 1997 Coll.
3) Organisation for Economic Cooperation and Development.
4) Act No. 246 / 1992 Coll., on the protection of animals against abuse, as amended by Act No. 162 / 1993 Coll. and Act No. 193 / 1994 Coll., and implementing regulations.
5) Paragraph 15 (2) of the ČNR Act No. 246 / 1992 Coll.
6) Act No. 246 / 1992 Coll., as amended.
7) Decree of the Ministry of Agriculture No. 311 / 1997 Coll., on the breeding and use of experimental animals.
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Regulation Information
| Citation | Decree of the Ministry of Health and the Ministry of Agriculture No. 74 / 1998 Coll., establishing good laboratory practice in the field of pharmaceuticals |
|---|---|
| Regulation Type | - |
| Author | - |
| Collection | Code of Laws |
| Date of Promulgation | 10.04.1998 |
|---|---|
| Effective from | 10.04.1998 |
| Effective until | - |
| Status | Valid |
The regulation text is for informational purposes only.
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