163/2012 Coll.
DECREE
Dated May 4, 2012
On Principles of Good Laboratory Practice
Ministry of Environment determined in accordance with § 17 para. 2 and § 20 paragraph
. 6 of the Act no. 350/2011 Coll., On chemical substances and mixtures
and amending some laws (chemical act)
§ 1
Subject Matter
This Decree implements the relevant regulations of the European Union ^ 1), while
follows directly applicable European Union regulations ^ 2) and regulates
A) Principles of Good Laboratory Practice (hereinafter "the Principles")
B) the conduct initial and periodic inspection and study audit
C) the scope of information to be provided at the initial and periodic inspection and audit
study
D) details progress reports and periodic input control and audit
study
E) certification model.
§ 2
Policy
(1) testing the hazardous properties of chemical substances and mixtures for
health and the environment for the Chemicals Act and
directly applicable European Union regulations ^ 2) apply the principles set out in Part A of Annex
to Decree no. 86/2008 Coll., on the principles of good laboratory practice
in pharmaceuticals.
(2) Model certificates issued pursuant to the Chemicals Act is set out in Annex
no. 1 hereto.
Initial and periodic inspection and audit studies
§ 3
(1) Before entry checks each employee
Ministry of the Environment set up a legal entity for validation principles (hereinafter referred
"certifying body") show proof of the employee certifies.
(2) In the initial inspection reveals that the test facility ^ 3)
has implemented a quality assurance program ^ 3) to ensure that studies carried
^ 3) are in compliance with the principles.
(3) Report on during incoming inspection test equipment includes
A) the name, address and identification number of the test device
B) the date on which the check was carried out,
C) the names and surnames of executives who attended
control
D) the subject of control
E) conclusions and recommendations concerning certification,
F) a statement of management of the test facility to report on the progress
input controls.
§ 4
(1) Before periodic inspections verifying each employee
person (hereinafter "the Inspector") show proof of the inspector.
(2) during periodic checks are reviewed and practices
test equipment on site to assess the degree of compliance with the principles.
Periodic inspections carried out at least once every two years; if
can not be serious reasons within this period to carry out inspection, carried out with
control as soon as possible by mutual agreement of the holder
certificate authenticating person.
(3) The audit study comparing primary data ^ 3) and related
records with the interim or final report on the results of a study with the aim
determine whether the raw data have been duly made and that the testing
carried out in accordance with the study plan ^ 3), and the standard operating procedures
^ 3); Audit studies are used to obtain additional information not contained
in the final report of the study results and determine whether they were when
data processing procedures in place, which could reduce their
validity.
(4) Progress report on the periodic inspection of the test facility includes
A) the name, address and identification number of the test device
B) the date on which the check was carried out,
C) the names and surnames of executives test facility who attended
control
D) the subject of control
E) conclusions and recommendations on maintaining or withdrawing the certificate
F) a statement of management of the test facility to report on the conduct periodic inspections
.
(5) Report on the course of study audit includes
A) the title of the study,
B) the name, address and identification number of the test device
C) the date when the audit was conducted,
D) the names and surnames of executives test facility who attended
audit
E) the subject of the audit,
F) conclusions and recommendations regarding the extent of compliance with the principles of the study,
G) a statement of management of the test facility to report on the progress of the audit.
§ 5
Course of introductory and periodic inspection and audit studies, including the extent
information provided is given in Annex no. 2.
§ 6
Efficiency
This Decree shall take effect on the fifteenth day after its publication.
Minister
:
Mgr. Cottage vr
Appendix 1
Model certificate
Appendix 2
Course of introductory and periodic inspection and study audit and the scope of information provided
^ 4)
First
Authenticating person
Authenticating person shall ensure that an adequate number of inspectors
, which depends on:
A) the number of test facilities involved in the compliance program
B) the frequency with which it is to be assessed the degree of conformity of test facilities
principles
C) the number and complexity of the studies undertaken by those test facilities,
D) the number of special inspections or audits requested
Ministry of Environment and Ministry of Health.
Authenticating person shall ensure the training of inspectors, taking into account their
individual qualifications and experience and participate
mutual consultation, including possible training to employees who certifies
in other OECD member countries.
Second
Compliance program
The compliance program is a detailed plan for monitoring compliance with the principles
test facilities through inspections and study audits.
Purpose of monitoring compliance with the principles is to determine whether the test facility
introduced in implementing the principles of studies and are capable of assuring that the resulting data should
adequate quality.
Third
Checking test equipment
Checks carried out on the land, the buildings and sites used for
testing to determine compliance with the principles may take place in any test
device that receives data on safety for health and the environment
for regulation, and has a certificate or they are requested.
Inspector may conduct an audit of data relating to physical,
chemical, toxicological and ecotoxicological properties of substances and mixtures
. During the inspection, reviewing the management structure and standard operating procedures
test facility with interviews with leaders
technical personnel assesses the quality and integrity of data generated by the facility and
served on them.
03.01 Control procedures
Preliminary checks
Before performing the test facility inspection or study audit, the inspector
familiar with the testing device, which has a visit.
Inspector will examine all reports of previous inspections, plans space
test facility, organization, reports on the results of studies and
list of employees.
Inspector focuses on information
A) the type, size and configuration of the test facility,
B) the scope of the studies, which will be addressed during the inspection,
C) the management structure of the test device.
Inspector focuses specifically on the shortcomings identified during previous inspections
test equipment. If there have been no previous
control serves preliminary review to obtain basic information.
03.02 Introductory meeting
Inspector at the initial meeting
A) outline the purpose and scope of the visit,
B) Description of documentation, such as in particular the lists of ongoing and
completed studies, study plans, standard operating procedures, reports
results of studies that will be required to check
test equipment; also agree on access to relevant documents and, if necessary, by
copying, illustrates the structure of a test
equipment or request information about the structure of the test equipment and
its employees,
C) require information on the studies, which do not apply the principle
carried out in areas of the test facility where the studies conducted under the principles
,
D) preliminarily determined which parts of the test device shall
control
E) describe the documents and specimens that will be needed for the audit of selected
ongoing or completed studies
F) announces that following the completion of the inspection will be held a final meeting.
Inspector before the commencement of the test equipment makes contact with
its quality assurance department.
When performing employee accompanies the inspector
quality assurance department.
03.03 Organization and personnel
Test facility management ^ 3) shall, upon request, these particular documents
A) floor plans,
B) organizational structure and management of specialist departments,
C) a list of employees involved in the studies selected for audit,
stating their qualifications
D) a list of ongoing and completed studies with information on the type
studies, launch dates and ukončení3) test system, 3) the method of application of test items
^ 3) and the name of the study, 3) | ||
E) programs of health surveillance,
F) workload of staff, their training programs and records
them
G) list of standard operating procedures in a test facility
H) specific standard operating procedures related to the studies or
procedures being inspected or audited,
I) a list of studies and leading sponsor of the survey, 3) which are subject
audit.
Inspector inspects especially
A) the conduct of ongoing and completed studies, to determine the level
work undertaken by the test facility,
B) the qualifications of the study director, head of QA
and other employees
C) the existence of standard operating procedures for all relevant areas of testing
.
04.03 Quality assurance program and QA
Director of QA on request illustrates
systems and methods for controlling and monitoring the quality assurance system
studios and recording observations made during the monitoring of the quality assurance
.
Inspector checks
A) the qualifications of the head of QA and all
employees of this department,
B) whether the QA unit functions independently from the staff involved in the
studies
C) how the QA unit schedules and conducts inspections, how
monitors identified critical phases of the study and what means has
available for inspection and monitoring quality assurance
D) whether, in the case of short-term studies, 3) when it is not practical to monitor
each study used random checks,
E) the extent and depth of QA monitoring during the practical phases of the study
,
F) the extent and depth of QA monitoring of routine activities
test device
G) QA procedure when checking reports on the results of the study
to confirm its compliance with the raw data,
H) that management receives from QA reports concerning
problems that may affect the quality or integrity of a study,
I) the measures taken by QA when finding
deviations
J) where QA role in the event that the study
or parts are done in contract laboratories,
K) any QA role in the review, revision or amendment
standard operating procedures.
05.03 Facilities
Inspector verifies whether
A) arrangement allows the particular test items, animal feed and
pathological specimens are sufficiently separated so that they do not
confused with those objects from another study
B) procedures exist maintenance and monitoring of environmental conditions and operating
effectively in critical areas, such as rooms for animals and
other biological systems in the premises for storing test
items and laboratories,
C) general cleaning in different areas sufficient, and that there are in
if necessary performs pest control.
06.03 Care of biological test systems, their location and isolation
Inspector checked by test systems that
A) the areas corresponding to the test systems used and needs
testing
B) conditions are created for the quarantine of animals and plants that have been
admitted to the testing facility, and whether these conditions are properly
argue
C) conditions are created for the isolation of animals, or other elements
test system, which are known or suspected of being sick or
transmitted diseases
D) there is adequate monitoring and registration of health, behavior or other aspects
test system
E) is adequate, well-maintained and efficient device for
maintaining the environmental conditions required for each test system
F) animal cages, nets, tanks and other containers and their accessories
Are kept sufficiently clean,
G) analyzes to check environmental conditions and support systems are
conducted in accordance with standard operating procedures,
H) facilities exist for removal of animal waste and waste
test systems, and whether they are treated so as to minimize
vermin infestation, odors, disease hazard and environmental contamination,
I) are storage areas for animal feed or equivalent
materials for all test systems; that these areas
not used for the storage of other materials such as test
items, chemicals, pesticides or disinfectants, and that
are separated from areas in which animals are housed or other biological
test systems,
J) stored feed and bedding are protected from deterioration
caused by adverse environmental conditions, infestation or contamination
.
07.03 Apparatus, materials, reagents and samples
Inspector verifies whether
A) the devices are clean and serviceable,
B) records are kept of operation, maintenance, verification, calibration and validation
measuring equipment and apparatus, including computer systems,
C) materials and chemical reagents are properly labeled and stored at appropriate temperatures
, and whether it complied with expiration date; whether labels
reagents should indicate their source, identity and concentration or other
relevant information
D) the specimens are well identified by test system, study,
origin and data collection,
E) the equipment and materials significantly affect the test
systems.
08.03 Test systems
3.8.1. Physical and chemical systems
Inspector verifies whether
A) was determined by the stability of test and reference položek3)
if required by the study plan, and whether they were used
reference items listed in the study plan,
B) data from automated systems, obtained in the form of graphs, recordings or
output from the computer are documented as raw data and are
archived.
3.8.2. Biological test systems
Taking account of aspects relating to care, placement
isolation and biological testing systems checks whether
A) test systems are in compliance with the specifications
study plans,
B) during the study test systems are adequately identified
way, if necessary, clearly, and that records exist regarding receipt
test systems and document fully the number of received,
used, replaced and discarded test systems
C) housing or containers for test systems are properly identified with all the necessary data
,
D) adequate separation of studies conducted on the same
animal species or the same biological test system but with different
substances
E) adequate separation of animal species
or other biological test systems in space and time
F) the biological test system environment in accordance with the plan
studies, or standard operating procedures, for example in terms
temperature or light mode,
G) records on the receipt, handling, housing or containment, care and health evaluation
apply to the relevant test systems,
H) are kept written records of examination, quarantine, morbidity, mortality
, behavior, diagnosis and treatment of animal and plant
test systems or other similar aspects as appropriate to each biological test
system || |
I) appropriate measures are taken for the removal of test systems
after completion of tests.
09.03 Test and reference items
Inspector checks whether
A) there are written records on the receipt of test and reference items
including the designation of the person responsible, and handling of test and reference items
, their sampling, usage and storage
B) the packaging test and reference items are properly labeled,
C) storage conditions are appropriate to preserve the concentration, purity and stability
test and reference items,
D) there are written records on the determination of identity, purity, composition, stability
test and reference items and appropriate records
protect them from contamination
E) if there are procedures for the determination of the homogeneity and stability
mixtures containing test and reference items,
F) if necessary, the container containing mixtures or solutions
test and reference items labeled and that records are kept on
homogeneity and stability of their contents,
G) in the case of a test that lasts longer than four weeks were
for analytical purposes samples from each batch ^ 3)
test and reference items, and whether they were kept for an appropriate time,
H) procedures are designed for mixing substances in order to avoid confusion or contamination
.
3.10 Standard operating procedures
Inspector checks whether
A) each part of the test equipment readily available appropriate
approved version of standard operating procedures
B) procedures exist for revision and updating standard operating procedures
,
C) are all additions and changes to standard operating procedures
authorized and dated,
D) retained the old version of standard operating procedures
E) there are standard operating procedures, especially for those activities
I) income, determination of identity, purity, composition and stability, marking
handling, sampling, usage and storage of test and reference
items
Ii) use, maintenance, cleaning, calibration and validation of measuring apparatus,
computerized systems and environmental control equipment,
Iii) preparation of reagents and dosage forms
Iv) record-keeping, reporting, storage and retrieval of records and reports
results of the study
V) preparation and environmental control in areas where there are
test systems
Vi) receipt, transfer, location, characterization, identification and care
test systems
Vii) handling of the test systems before the study, in its
during and after its completion,
Viii) disposal of test systems
Ix) use of pest control and cleaning
use of resources
X) of the department of quality assurance.
3.11 Conduct studies
Inspector verifies whether
A) the study plan was signed by the study,
B) all amendments to the study plan signed and dated by
study
C) in case of need recorded date with the consent of the contracting
study plan,
D) the measurement, observation and tests in accordance with the study plan and
appropriate standard operating procedures,
E) the results of these measurements, observations and tests were recorded directly
immediately, correctly and legibly and were signed or initialed and dated
,
F) any changes in the raw data, including data stored in computers,
overlap the previous figures are given the reasons for the changes
identification of the person responsible for the change and the date it was made,
G) data have been identified by computer or
therein, whether they are sufficient procedures to protect them against unauthorized changes
or losses
H) are computer systems used in the study reliable, accurate and validated
,
I) were examined and evaluated
any unforeseen events recorded in the raw data,
J) the results are presented in the reports on the results of the study (interim or final
) consistent and complete, and that exactly correspond to the primary
data.
3.12 Reports on the results of the study
When reviewing reports on the results of the study inspector checks whether
A) is signed and dated by the study as proof
assumption of responsibility for the validity of the study and confirming that the study was conducted in accordance with the principles
,
B) is signed and dated by other specialized personnel if they are
it includes reports from cooperating industry
C) a report on the results of the study indicated a statement of assurance
quality, and that it is signed and dated,
D) all changes made to the responsible employees
E) specifies the location of all samples, samples of test System3) and
primary data.
3.13. Storage and retention of messages on the results of the study
Inspector checks
A) whether the designated person responsible for filing,
B) filing space for storage of study plans, raw data
Including data from the interrupted studies carried out in accordance with the principles
reports on the results of the study, samples, samples of test systems and records
education and training of employees,
C) the procedures for retrieval of materials,
D) the procedures for limiting access to only authorized filing
employees and records of employees who have been allowed access to
raw data, Slide accessories and other materials from filing,
E) whether the maintenance of an inventory of materials issued from the registry and returned to
her
F) whether the records and materials retained for the required or appropriate
period of time and are especially protected against loss or damage by fire and
adverse environmental conditions.
Fourth
Study audit
Inspections of test facilities include a study audits, which review
ongoing or completed studies. The objective is
reconstruction study comparing reports on the results of studies with a plan
studies, the appropriate standard operating procedures, primary
data and other stored material. The inspector does not cover professional
design of the study and interpretation of the results of studies with respect
risk for human health and the environment.
When conducting a study audit provides test equipment
A) the names, job descriptions and summaries of training and experience
selected employees who participated in the study, as leading
studies and scientific staff
B) evidence that there is a sufficient number of qualified employees
in areas in which there is a study
C) identification of individual components of apparatus or special
equipment used in the study and records of calibration, maintenance and service
device
D) records of stability of test items, the analyzes of these substances and their
composition, analyzes of feed, etc.,
E) the breakdown of the tasks to be assigned to selected employees who
participating in the study to determine whether these employees have enough
time to accomplish the tasks specified in the study plan or report on the results
study | ||
F) copies of all documentation concerning control procedures or
which forms an integral part of the study, especially
I) the study plan,
Ii) standard operating procedures that were used in the implementation
study
Iii) logbooks, laboratory notebooks, files
, worksheets, outputs from data stored in computers and
other similar data, if necessary, checking calculations,
Iv) report on the results of the study.
In studies on animals, such as rodents and other mammals
monitors inspector sufficiently meaningful percentage of animals from
their arrival at the test facility to autopsy.
Pays particular attention to the records relating
A) animal body weight, food and water intake, preparation
application rates and their administration,
B) clinical observations and autopsy findings,
C) clinical chemistry,
D) pathology.
Fifth
The follow-up test facility inspection or study audit
05.01 If there were no or only very small deviations
verifying person
A) a statement that the test facility has been inspected and
it was found that the test facility is operating in compliance with the principles;
Indicate the date of the test facility inspection and study
or subjected to scrutiny; such declaration shall also provide information
authorities for monitoring compliance with good laboratory practice
in other OECD member countries,
B) impose a test facility to remedy the identified deviations
C) provide the Ministry of the Environment a detailed report on the results
identified.
05.02 If you are serious deviations that can not affect the validity
studies conducted in the test facility, to verify the person
A) notify the Ministry of the Environment
detail of observed inadequacies or faults and recommend suspension of certificates
to remedy the deficiencies
B) impose a test facility to remedy the identified deviations, but not later than six months
. After rectification performed to verify the person
control their removal. During the removal of shortcomings is not
test equipment is out of compliance program
C) provide the Ministry of the Environment a detailed report of findings
results
D) provide the Ministry of the Environment separate report on the removal
control deviations. If there were deviations
satisfactorily removed, proceed to verify the person pursuant to section 5.3.
05.03 If they are serious deviations that may affect
validity of studies conducted in the test facility, to verify the person
A) notify the Ministry of the Environment
detail of observed inadequacies or faults and recommend revocation of the certificate and end
inspections of the test facility or study audits and test facility decommissioning
a compliance program
B) Ministry of the Environment recommends that a study be rejected, or
C) requests that the reports on the results of studies
accompanied by a statement detailing the deviations.
1) Directive of the European Parliament and Council Directive 2004/9 / EC of 11 February
2004 on the inspection and verification of good laboratory practice.
Directive of the European Parliament and Council Directive 2004/10 / EC of 11 February 2004
on the harmonization of the laws and regulations regarding the use
principles of good laboratory practice and the verification of their application for tests on chemical substances
.
2) Regulation of the European Parliament and Council Regulation (EC) no. 1907/2006 of 18
December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals
, establishing a European Chemicals Agency, on
amending Directive 1999/45 / EC and repealing Council Regulation (EEC) no. 793/93
Commission Regulation (EC) no. 1488/94, Council Directive 76/796 / EEC and Directives
Commission 91/155 / EEC, 93/67 / EEC, 93/105 / EC and 2000/21 / EC, as amended.
Regulation of the European Parliament and Council Regulation (EC) no. 1272/2008 of 16
December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives
67/548 / EEC and 1999 / 45 / EC, and amending Regulation (EC) No.
1907/2006, as amended.
3) Decree no. 86/2008 Coll., On the principles of good laboratory practice
in pharmaceuticals.
4) Provisions on the course entrance and periodic inspections and audits and studies
extent of the information contained in this Annex
are in accordance with Annex I of the Directive of the European Parliament and Council Directive 2004/9
/ EC of 11 February 2004 on the inspection and verification of good laboratory practice
(codified version).
