Decree of the Ministry of Health and the Ministry of Agriculture No. 504 / 2000 Coll.

Q: Is Decree of the Ministry of Health and the Ministry of Agriculture No. 504 / 2000 Coll. still valid?

Yes, Decree of the Ministry of Health and the Ministry of Agriculture No. 504 / 2000 Coll. is still valid and effective.

504

DECLARATION

Ministry of Health and Ministry of Agriculture

of 22 December 2000

establishing good laboratory practice in the field of pharmaceuticals

The Ministry of Health and the Ministry of Agriculture provides, pursuant to § 75 (2) (c) of Act No. 79 / 1997 Coll., on Medicines and on amendments and additions to certain related laws, as amended by Act No. 149 / 2000 Coll., hereinafter referred to as "the Act ':

§ 1

Preliminary provisions

(1) Good laboratory practice means a set of rules constituting a system of work in the conduct of preclinical studies on the safety of medicinal products; These rules concern the organisation process and the conditions under which such studies are planned, implemented, controlled, recorded, submitted and archived.

(2) For the purposes of this Order, the following definitions shall also apply:

(a) testing equipment - persons, premises and equipment necessary for carrying out studies. In the case of multiple-site studies, a test facility means the location of the study leader and all individual test sites which may be considered as test equipment individually or as a whole,

(b) testing site - place where the individual stages of the study are carried out;

(c) the head of the testing facility - the person responsible for the organisation and operation of the test facility in accordance with this decree and having the necessary powers;

(d) the head of the test site - the person who ensures that the phase of the study for which he is responsible is carried out in accordance with this decree; the head of the test site shall be appointed if the study is conducted in several locations;

(e) by the contracting authority - the person ordering, providing and submitting the study financially;

(f) study leader - natural person responsible for the overall conduct of the study,

(g) the head of the partial examination - a natural person who, if the study is carried out in several places, acts on behalf of the study leader and is responsible for the specified stages of the study;

(h) quality assurance programme - a defined system independent of the conduct of a study which serves to ensure compliance with these principles by the head of the testing facility and includes staff;

(i) standard operating procedures - documented procedures describing how to perform tests or activities not detailed in the study plan or in the test instructions;

(j) a list of studies - the information collected to plan the activities and to monitor the studies in the testing facility;

(k) studies - test or set of tests which test an item tested under laboratory conditions or in the environment in order to obtain data on its properties and safety for submission to the competent authority, 1)

(l) short-term studies - a short-term study using routine and widely used methods;

(m) study plan - a document defining the objective of the study and the design of its experimental implementation, including additions;

(n) a supplement to the study plan - documented intended change to the study plan after the date of commencement of the study,

(o) deviation from the study plan - unintended change from the study plan after the start of the study,

(p) testing system - any biological, chemical or physical system or combination thereof used in the study;

(q) primary data - any original records and documentation or certified copies thereof obtained in the testing facility as a result of observations and activities during the study. The primary data may include photographs, microfilms or copies of microlabels, records on electronic media, dictated observations, automatic instrument records or records on any other media storing data that are normally considered safe for the retention of information for the period specified in Annex Part II, Section 10,

(r) a sample of the test system - any material obtained from the test system for testing, evaluation or storage;

s) study start date - the day on which the study manager signed the study plan,

(t) the date of experimental initiation of the study - the date on which the first data related to the study were obtained,

(u) date of experimental study termination - the last day on which data related to the study were obtained;

(v) the date of completion of the study - the date on which the study leader signed the final report,

(w) tested item - the material which is the subject of the study,

(x) reference item - material to be used for comparison with the tested item,

(y) batches - specific quantity or part of the tested or reference item, prepared in a defined production cycle in such a way that its uniform characteristics can be assumed and appropriately marked;

(z) vehicle - any substance with which the test or reference item is mixed or in which it is dissolved or dispersed to facilitate its application to the test system.

§ 2

(1) Laboratory tests for non-clinical drug safety testing shall be carried out in accordance with the principles of good laboratory practice (hereinafter referred to as "the principles') set out in the Annex.

(2) Animal testing shall be carried out in the testing facility in accordance with the special legislation.2)

(3) In an inspection activity assessing the conditions of good laboratory practice in establishments and in testing systems working with live vertebrates, the participation of the person certified by the competent animal protection authority under the special legislate.3)

§ 3

The State Institute for Drug Control shall keep a list of operators holding certificates certifying compliance with the conditions of good laboratory practice and record the checks carried out. The list valid on 31 December of each calendar year and the control report for the previous calendar year shall be published annually by the end of March of the following year in the Bulletin of the State Institute for Drug Control.

§ 4

Decree No. 74 / 1998 Coll., establishing good laboratory practice in the field of pharmaceuticals, is hereby repealed.

§ 5

This decree shall take effect on 1 January 2001.

Minister for Health:

Prof. MUDr. Fisher, CSc.

Minister for Agriculture:

Ing. Fencl v. r.

Annex to Decree No 504 / 2000 Coll.

A. PRINCIPLES OF CORRECT LABORATORY PRACTICE

INTRODUCTORY PROVISIONS

1. Range

According to the principles of good laboratory practice, non-clinical testing of test items contained in human or veterinary medicinal products shall be carried out. These test items are of natural origin, biological origin or synthetic chemicals; may also be live organisms. The purpose of testing these test items is to obtain data on their properties and safety with regard to human, animal and environmental health.

Non-clinical safety studies with an impact on health and the environment (hereinafter referred to as "studies') covered by these principles relate to the work carried out in laboratories, greenhouses and fields.

These principles apply to all studies required to register medicinal products.

PRINCIPLES OF CORRECT LABORATORY PRACTICE

("Principles of Good Laboratory Practice OECD," OECD Environmental Section 1, adopted on 26.11.1997 by the OECD Council [C (97) 186 (Final).)

1. Organisations and staff of the testing facility

1.1. Head of Test Device

1.1.1. The test equipment manager shall ensure compliance with these principles in the relevant test equipment.

1.1.2. The head of the testing facility shall, within the scope of his or her competence, ensure:

(a) that a document designating it as the person responsible for conducting the test equipment is available in accordance with these principles;

(b) that qualified staff are available as well as premises, equipment and materials enabling the study to be carried out in a timely and proper manner;

(c) keeping documentation on the qualifications, training and experience of all professional and technical staff, including descriptions of their work;

(d) staff members shall understand the activities to be carried out and, where necessary, train the staff members;

(e) that the technical standard operating procedures in force are developed and complied with and approved by those procedures, whether original or revised;

(f) that a quality assurance programme is implemented, including the identification of the persons responsible for the programme, and that quality assurance is carried out in accordance with these principles;

(g) prior to the start of each study, the appointment of a study leader who has the appropriate qualifications, training and experience; the replacement of the study leader shall be carried out according to the procedures laid down and documented;

(h) in the case of multiple-site studies, the appointment of a study leader who has the appropriate qualifications, training and experience to supervise the studies entrusted to him; the replacement of the head of the subtest shall be carried out according to the procedures laid down and documented;

(i) documented approval of the study plan by the study leader;

(j) that the study manager has made the approved study plan available to quality assurance staff;

(k) keeping all valid and invalid versions of standard operating procedures in at least one specimen;

(l) the appointment of the staff responsible for keeping the archive,

(m) the registration of studies and the retention of their list;

(n) that supplies to the testing facility meet the requirements for their use in the study;

(o) that there are clear ways of exchanging information between the study leader, the study leader, the quality assurance programme manager and other staff involved in the study;

(p) characterisation of the tested and reference items.

1.1.3. The head of the testing facility shall, within its scope, establish procedures to ensure that computer systems are suitable for the intended purpose and are validated, used and maintained in accordance with these principles.

1.1.4. The head of the test site shall assume responsibility at the test site for the provision of the activities of the head of the test facility, with the exception of those referred to in point 1.1.2. (g), (i), (j) and (o).

1.2. Study Manager

1.2.1. The study leader is the only study director and is responsible for the overall implementation and final study report.

1.2.2. The study leader shall approve the study plan and any additions to the study plan within the scope of his or her competence and shall bear his or her signature and date.

1.2.3. The study leader shall ensure, within his or her competence, that:

(a) the quality assurance staff shall have a copy of the study plan and any additions to it in due time and the study manager shall cooperate effectively with quality assurance staff during the study;

(b) staff involved in the study have a study plan at their disposal prior to its experimental initiation, all its supplements and standard operating procedures;

(c) the multi-site study plan and its final report identify and define the roles of all subtesting leaders, all test facilities and test points where the study is conducted;

(d) comply with the procedures set out in the study plan, assess and document the impact of any deviations from the study plan on the quality and integrity of the study and, where necessary, implement corrective actions; evaluate and confirm deviations from standard operating procedures during the study;

(e) all primary data obtained are fully documented and recorded;

(f) computer systems used in the study are validated;

(g) a study plan, final report, primary data and supporting material are archived after completion of the study.

1.2.4. The study leader shall confirm the final report by signing it, indicating its date, thereby assuming responsibility for the validity of the data and indicating the extent of compliance of the study with these principles.

1.3. Head of Partial Testing

The head of the partial examination shall ensure that the studies entrusted to him are carried out in accordance with these principles. The responsibility of the study leader for the overall conduct of the study cannot be transferred to the study leader; In particular, the responsibility for approving the study plan and its additions, approving the final report and stating that these principles have been respected cannot be delegated,

1.4. Studies staff

1.4.1. All staff performing a study shall be familiar with those parts of the principles which relate to their role in the study.

1.4.2. The study staff shall have access to the study plan and the relevant standard operating procedures they use when carrying out the study. They are responsible for following these documents. Any deviation from these documents shall be recorded and reported to the study leader or, where appropriate, to the study director.

1.4.3. The study staff shall be responsible for the prompt and accurate recording of the primary data, the quality of those data and compliance with these principles.

1.4.4. The study staff shall follow measures to minimise the risk to their health and to ensure the integrity of the study. Staff members shall notify changes in their state of health to the relevant person who shall decide to exclude staff members from those activities which may affect the study.

2. Quality assurance programme

2.1. General

2.1.1. The testing equipment has a documented quality assurance programme guaranteeing that studies are carried out in accordance with these principles.

2.1.2. The quality assurance programme shall be carried out by the staff member or staff directly subordinate to the head of the testing facility and shall be well aware of the testing procedures.

2.1.3. Staff who ensure the quality of the study cannot participate in its implementation.

2.2. Quality assurance staff

2.2.1. Quality assurance staff within their competence:

(a) keep copies of any agreed study plans and standard operating procedures used in the testing facility and have access to a simultaneously valid copy of the study list;

(b) verify that the study plan contains the information required to comply with these principles; the verification shall be documented;

(c) carry out inspections to determine whether all studies are carried out in accordance with these principles; inspections shall also examine whether the study staff are available and follow study plans and standard operating procedures.

The inspections shall be divided into three categories to be described in the standard operational procedures of the quality assurance programme:

(i) inspection of studies;

(ii) inspection of premises and facilities;

(iii) process inspections; records of such inspections shall be kept;

d) check the final reports and confirm that the methods, procedures and observations are described faithfully and accurately and that the recorded results accurately and fully reflect the primary study data;

(e) report without delay all results of inspections to the head of the testing facility and to the head of the study, and, where appropriate, to the head of the partial testing and to the head of the test site,

(f) issue and confirm a declaration accompanying the final report indicating the categories of inspections and the dates of their implementation, including the phase of the study to be inspected, the date of notification of the results of the inspections to the head of the testing establishment and to the head of the study and, where appropriate, to the head of the partial testing. This statement also confirms that the final report reflects primary data.

3. Space

3.1.

3.1.1. The test equipment has spaces of such size, design and location as to meet the requirements of the study and to minimise disruptive factors which may adversely affect the validity of the study.

3.1.2. The premises are arranged in such a way that the degree of separation of different activities ensures that each study is properly carried out.

3.2. Space for test systems

3.2.1. The test system spaces shall have a number of rooms or sections to ensure the separation of test systems and individual projects using materials or organisms known or suspected to be biologically hazardous.

3.2.2. There are rooms or sections for diagnosis, treatment and control of the disease to ensure that testing systems are not unduly impaired.

3.2.3. Storage facilities for supplies and facilities are available. The storage facilities shall be separated from the rooms or sections in which the test systems are located and shall ensure appropriate protection against pest infestation, contamination and degradation.

3.3. Spaces for the treatment of test and reference items

3.3.1. Separate spaces for receiving and storing tested and reference items and for mixing tested items with vehicle are set aside to prevent contamination or confusion.

3.3.2. The storage spaces for the tested items are separate from those for the test systems so as to maintain the identity, concentration, purity and stability of the tested items and ensure safe storage of hazardous substances.

3.4. Archive spaces

The archive rooms shall be equipped to ensure the safe storage and searching of study plans, primary data, final reports, samples of tested items and samples of test systems. Archive design and archival conditions are designed to protect archived material from premature deterioration.

3.5. Waste disposal 4)

The handling and disposal of waste shall be in such a way as not to jeopardise the integrity of studies; This includes ensuring space for collection, storage and disposal of waste and procedures for decontamination and transport.

4. Instruments, materials and reagents

4.1. Apparatus, including validated computer systems, used for the acquisition, storage and generation of data and for monitoring of study-related environments shall have design and capacity commensurate with the needs of the study.

4.2. The apparatus used in the study is regularly checked, cleaned, maintained and calibrated according to standard operating procedures. Records of such activities shall be kept. Calibration, if possible, shall be linked to national or international measurement standards.

4.3. Instruments and materials used in the study will not adversely affect test systems.

4.4. Chemicals, reagents and solutions shall be identified by name or concentration, where appropriate, by indication of the shelf life and instructions on specific storage conditions. Data on origin, dates of preparation and stability are also available. The period of application may be extended on the basis of documented testing or analysis.

5. Test Systems

5.1. Physical and Chemical

5.1.1. The location and characteristics of the instruments used to obtain chemical and physical data are consistent with the needs of the study; their design and capacity are proportionate to the purpose of use.

5.1.2. The integrity of physical and chemical testing systems shall be ensured.

5.2. Biological

5.2.1. Good conditions shall be established and maintained for the location, housing, treatment and handling of biological testing systems to ensure the quality of the data.

5.2.2. Newly acquired animal and plant testing systems shall be isolated until their health status has been assessed. If an unusual mortality or disease occurs, the supply shall not be used for studies and, where appropriate, test systems for killing in accordance with specific legislation.2) In the experimental initiation of the study, test systems are free from any disease or condition that could adversely affect the purpose or course of the study. Test systems that become ill or injured during the study shall be isolated or treated if necessary to maintain the integrity of the study. All diagnoses and treatments for any disease prior to or during the study are noted.

5.2.3. Records of the source, date and conditions of supply of test systems shall be kept.

5.2.4. Biological test systems shall be adapted to test conditions for a reasonable period prior to the first administration (application) of the tested or reference item.

5.2.5. Any information necessary to properly identify the test systems shall be provided on their cages or containers. Individual test systems that are removed from cages or containers during the study shall be marked as far as possible.

5.2.6. The use of bedding and the cleaning of cages and containers for test systems shall comply with specific legislation. 5)

5.2.7. Test systems used in field studies shall be located in such a way as to avoid disrupting the study with spray and prior use of plant protection products. 6)

6. Test and reference items

6.1. Reception, handling, sampling, storage

6.1.1. Data shall be recorded and stored characterising the test and reference items, their intake dates, shelf life, the quantities received and the quantities used in the studies.

6.1.2 Handling, sampling and storage shall be carried out in such a way as to avoid any confusion and contamination and ensure an acceptable degree of homogeneity and stability.

6.1.3. The storage containers shall bear identification information, shelf life and specific storage instructions.

6.2. Characterisation

6.2.1. Each test and reference item is identified accordingly, e.g. by code, CAS (Chemical Abstracts Service Registry Number), name, biological parameters, etc.

6.2.2. For each study, the identity of the tested or reference item, including batch number, purity, concentration or other parameters that define each batch accordingly, shall be known.

6.2.3. In cases where the tested item is supplied by the contracting authority, the procedure developed jointly by the contracting authority and the testing facility to verify the identity of the tested item subject to the study shall be established.

6.2.4. The stability of the tested and reference items under storage and testing conditions is known for all studies.

6.2.5. If the tested item is administered or administered in a vehicle, the homogeneity, concentration and stability of the tested item in that vehicle shall be determined; for test items used in field studies, e.g. mixtures in tanks these parameters may be determined by means of separate laboratory tests.

6.2.6. For all studies except short-term studies, samples from each batch of tested items shall be kept for analytical purposes.

7. Standard operating procedures

7.1. The test equipment shall have written standard operating procedures approved by the test leader to ensure the quality and completeness of the data generated in the test equipment. Revision of standard operational procedures shall be approved by the head of the testing facility.

7.2. Each part of the test equipment has a valid version of the standard operating procedures applicable to the activities carried out here for immediate use. The Annexes to these standard operating procedures may include published textbooks, analytical methods, publications and manuals.

7.3. Derogations from standard operating procedures relating to the study shall be documented and confirmed by the study leader or, where appropriate, by the study supervisor.

7.4. Standard operating procedures are available in particular for the following activities in the test equipment:

7.4.1. Test and reference items

Receipt, authentication, marking, handling, sampling and storage.

7.4.2. Instruments, materials and reagents

(a) instruments

operation, maintenance, cleaning and calibration,

(b) computer systems

validation, operation, maintenance, reliability, change management and backup;

(c) materials, reagents and solutions

preparation and marking.

7.4.3. Record keeping, recording, storage and searching

Study encoding, data collection, news preparation, index systems, data manipulation including the use of computer systems.

7.4.4. Test systems (if applicable)

(a) room preparation and environmental conditions for the testing system;

(b) procedures for the reception, transmission, proper location, characterisation, identification and care of the test system;

(c) preparation of the test system, observations and examinations at the beginning, during and at the end of the study;

(d) the treatment of subjects of the test system found dying or dead during the study;

(e) collection, identification and handling of samples of the test system, including autopsy and histopathology;

(f) the location of the test systems in the testing equipment space plan.

7.4.5. Quality assurance procedures

Quality assurance staff procedures for planning, layout, implementation, documentation and method of recording inspections.

8. Performing the Study

8.1. Study Plan

8.1.1. There is a written study plan for each study before it is initiated. The study plan shall be approved by signature of the study manager, indicating the date of signature, and shall verify compliance with these principles by the quality assurance staff as set out in paragraph 2.2.1. (b).

Citation	Decree of the Ministry of Health and the Ministry of Agriculture No. 504 / 2000 Coll., establishing good laboratory practice in the field of pharmaceuticals
Regulation Type	Order
Author	-
Collection	Code of Laws

Date of Promulgation	30.12.2000
Effective from	01.01.2001
Effective until	-
Status	Valid

Decree of the Ministry of Health and the Ministry of Agriculture establishing good laboratory practice in the field of pharmaceuticals

Contents

§ 1

§ 2

§ 3

§ 4

§ 5

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