good laboratory practice - 195.134.76.37
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In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
Good Laboratory Practice
Evsevios Hadjicostas
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
1
Good Laboratory Practice
Good Laboratory Practice (GLP) is a quality system concerned with the organizational process and the conditions under which a study is planned, performed, monitored, recorded, archived and reported.
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
2
History of GLP
First in US after irregularities in pharmaceutical companiesOther countries followed
To increase trustTo be able to export to US
OECD (Organization for the Economic Cooperation and Development)
First decision in 1981Binding guidelines in 1989
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
3
Why GLP?
Development of quality test data Mutual acceptance of dataAvoid duplication of dataAvoid technical barriers to tradeProtection of human health and the environment
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
4
Scope
Non-clinical safety testing of test items contained in
Pharmaceutical productsPesticide productsCosmetic productsVeterinary drugsFood and feed additivesIndustrial chemicals
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
5
The European Commission Directive 2004/9/EC
EU Member States shall verify the compliance with GLP of any testinglaboratory within their territory claiming to use GLP in the conduct of tests on chemicals
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
6
Inspection and Audit
The authorities of the EU Member States shall inspect the laboratory and audit the studies in accordance with theprovisions laid down in Annex I of the Directive 2004/9/EC
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
7
Directive 2004/9/EC Annex I, Part A
Guides for compliance monitoring procedures for good laboratory practice
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
8
Directive 2004/9/ECAnnex I, Part B
Guidance for the conduct of test facility inspections and study audits
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
9
The Commission Directive 2004/10/EC
The harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests onchemical substances
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
10
The GLP Principles
1. Test facility organization and personnel2. Quality Assurance (QA) program3. Facilities4. Apparatus, materials and reagents5. Test systems6. Test and reference items7. Standard Operating Procedures (SOP’s)8. Performance of the study9. Reporting of study results10. Storage and retention of records and materials
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
11
Terms Concerning the Organization of a Test Facility
Test facilityTest siteTest facility managementTest site managementSponsorStudy directorPrincipal investigatorQuality assurance programStandard operating proceduresMaster schedule
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
12
Terms Concerning the StudyNon-clinical health and environmental safety studyShort term studyStudy planStudy plan amendmentStudy plan deviationTest systemRaw dataSpecimenExperimental starting dateExperimental completion dateStudy initiation dateStudy completion date
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
13
Terms Concerning the Test Item
Test item: the article that is subject of a studyReference itemBatch Vehicle
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
14
1. Test Facility Organization and Personnel
Test facility management’s responsibilitiesStudy director’s responsibilitiesPrincipal investigator’s responsibilitiesStudy personnel’s responsibilities
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
15
The management should ensure that The principles of GLP are complied withA sufficient number of qualified personnel, appropriate facilities, equipment and materials are availableRecords of qualifications, job descriptions, training and experience of personnel are maintainedPersonnel understand the functions they are to perform
1. Test Facility Organization and PersonnelTest Facility Management’s Responsibilities
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
16
1. Test Facility Organization and PersonnelTest facility Management’s Responsibilities
Appropriate and valid SOP’s are established and followed A Quality Assurance Program is in placeA Study Director and a Principal Investigator, if needed, is designatedDocumented approval of the study planThe study plan is available to quality assurance personnel
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
17
1. Test Facility Organization and PersonnelTest Facility Management’s Responsibilities
A document control system is in placePurchased materials meet specified requirementsTest and reference items are appropriately characterizedClear lines of communication existComputerized systems are suitable for their intended purpose
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
18
1. Test Facility Organization and PersonnelStudy Director’s Responsibilities
Has the responsibility for the overall performance of the study and the final reportApproves the study plan and amendments and communicate them to the QA personnel Ensures that SOPs, study plans and their amendments are available to study personnelEnsures that the SOPs are followed, assess the impact of any deviations and takes appropriate corrective and preventive action
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
19
1. Test Facility Organization and PersonnelStudy Director’s Responsibilities
Ensures thatRaw data are documented and recordedComputerized systems are validatedSOPs are followedDeviations are acknowledgedRecords and data are archived
Sign and date the final report to indicate acceptance of responsibility
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
20
1. Test Facility Organization and PersonnelStudy Personnel Responsibilities
Knowledge of the GLP principalsAccess to the study plan and appropriate SOPsComply with the instructions of the SOPsRecord raw dataStudy personnel are responsible for the quality of their dataExercise health precautions to minimize riskEnsure the integrity of the study
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
21
2. Quality Assurance ProgramGeneral
Documented Quality Assurance (QA) ProgramDesignated individuals as members of the QA team directly responsible to the managementQA members not to be involved in the conduct of the study being assured
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
22
2. Quality Assurance ProgramResponsibilities of the QA Personnel
Access to the updated study plans and SOPsDocumented verification of the compliance of study plan to the GLP principalsInspections to determine compliance of the study with GLP principles. Three types of inspection
Study-based inspectionsFacility-based inspectionsProcess-based inspections
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
23
2. Quality Assurance ProgramResponsibilities of the QA Personnel
Inspection of the final reports for accurate and full descriptionReport the inspection results to the managementStatement
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
24
3. FacilitiesSuitable size, construction and locationAdequate degree of separation of the different activitiesIsolation of test systems and individual projects to protect from biological hazardsSuitable rooms for the diagnosis, treatment and control of diseasesStorage rooms for supplies and equipment
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
25
3. FacilitiesSeparate areas for receipts and storage of the test and reference itemsSeparation of test items from test systemsArchive facilities for easy retrieval of study plans, raw data, final reports, samples of test items and specimenHandling and disposal of waste in such a way not to jeopardize the integrity of the study
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
26
4. Apparatus, Materials and ReagentsApparatus of appropriate design and adequate capacityDocumented inspection, cleaning, maintenance and calibration of apparatus. Calibration to be traceable to national or international standardsApparatus and materials not to interfere with the test systemsChemicals, reagent and solutions should be labeled to indicate identity, expiry and specific storage instructions.
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
27
5. Test Systems
Physical and chemical test systemsAppropriate design and adequate capacity of apparatus used for the generation of dataIntegrity of physical/chemical test systems
Biological test systemsProper conditions for storage, housing, handling and careIsolation of newly received animal and plant test systems until health status is evaluatedHumanely destruction of inappropriate test systems
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
28
5. Test SystemsRecords of source, date of arrival, and arrival conditions of test systemsAcclimatization of biological systems to the test environmentProper identification of test systems in their housing or container or when removedCleaning and sanitization of housings or containers Pest control agents to be documentedAvoid interference from past usage of pesticides
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
29
6. Test and Reference Items
Receipt, handling, sampling and storageRecords for date of receipt, expiry date, quantities received and used in studies etc.Handling, sampling and storage procedures to ensure homogeneity and stability and avoid contamination or mix-upIdentification information on storage containers
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
30
6. Test and Reference ItemsCharacterization
Identification of each test and reference item
Code, CAS number, name etc.Identification of each batch of the test or reference items
Batch number, purity, composition, concentration etc.
Cooperation between the sponsor and the test facility
Verification of identity of the test item
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
31
6. Test and Reference Items
Known stability of test and reference itemsStability of the test item in its vehicle (container)Experiments to determine stability in tank mixers used in the field studiesSamples for analytical purposes for each batch
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
32
7. Standard Operating Procedures
Approved SOPs to ensure the quality and integrity of the laboratory dataImmediately available current SOPs relevant to the activities being performedDeviations from SOPs to be acknowledged by the study director
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
33
7. Standard Operating Procedures
SOPs forTest and reference items
Receipt, identification, labeling, handling, sampling, storage
ApparatusUse, maintenance, cleaning, calibration
Computerized systemsValidation, operation, maintenance, security, change control, back-up
Materials, reagents and solutionsPreparation and labeling
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
34
7. Standard Operating Procedures
Record keeping, reporting, storage and retrieval
Coding system, data collection, preparation of reports, indexing system, handling of data
Test systemRoom preparation, environmental room conditions, receipt, transfer, identification etc., test system preparation, observations etc.,
Quality Assurance ProceduresOperation of QA personnel
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
35
8. Performance of the StudyStudy plan
Written plan, verified for GLP compliance, approved by the study director and by the managementApproval of amendments by dated signaturesDeviations to be explained and acknowledged
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
36
8. Performance of the Study
Content of the study planIdentification of the study
Title, nature and purpose of the study, test item identity, reference item used etc.
Information concerning the sponsor and facilityNames and address (sponsor, test facility, study director)
DatesApproval dates of the study plan, estimated starting and completion dates etc.
Reference to test methodsRecords
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
37
8. Performance of the Study
Conduct of the studyIdentification of each studyThe study to be conducted in accordance with the study planData generated to be recorded directly and accuratelyChanges in the raw data not to obscure the previous dataIdentification of electronic data
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
38
9. Reporting of Study ResultsGeneral
Final report for each studyScientists to sign and date their reportsApproval by the Study DirectorCorrections, additions, amendments to be signed and dated by the study director
Content of the final reportIdentification of the study
Descriptive title, identification of the test and reference item, purity, stability
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
39
9. Reporting of Study ResultsInformation on sponsor and test facility
Name and addresses of the sponsor, test facility, study director, the scientists involved to the study etc.)
Experimental starting and completion datesA Quality Assurance Program statementDescription of materials and test methodsResults
Including uncertainties, level of significanceEvaluation discussion and conclusions
Storage (of samples, reference items, raw data, final reports etc.)
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
40
10. Storage and Retention of Records and Materials
What to retain in archivesThe study plan, raw data, samplesInspection data and master schedulesQualification, training experience, job descriptionMaintenance and calibration dataValidation dataSOPsEnvironmental, health & safety monitoring records
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
41
10. Storage and Retention of Records and Materials
Retention period to be definedIf any study material is disposed of before expiry the reason to be justified and documentedIndex of materials retained in the archivesControlled access to the archivesIn case that the laboratory goes out of business the archives are transferred to the relevant sponsor(s)
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
42
Summary
GLP v/v ISO 9000 and ISO 17025Non-clinical health and environmental safety studiesPhysical and chemical test systemsBiological test systemsOECDEU Directive 1999/11/EC
In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and Teaching (2nd ed.)
Hadjicostas, E.: Good Laboratory Practice © Springer-Verlag, Berlin Heidelberg 2010
43
Where to Get More InformationCommission Directive 2004/9/EC and Commission Directive 2004/10/EC
http://eur-lex.europa.euhttp://ec.europa.eu/enterprise/chemicals/legislation/glp/index_en.htmhttp://www.oecd.org under environment/chemical safety