[4] Good Laboratory Practice

Good Laboratory Practice (GLP)

quality system concerned with the organizational process and the conditions under which a study is planned, performed, monitored, recorded, archived and reported.

Good Laboratory Practice (GLP)

• First in US after irregularities in pharmaceutical companies

• Other countries followed: To increase trust; To be able to export to US

• OECD (Organization for the Economic Cooperation and Development): First decision in 1981; Binding guidelines in 1989

• Development of quality test data

• Mutual acceptance of data

• Avoid duplication of data

• Avoid technical barriers to trade

• Protection of human health and the environment

Why GLP?

Non-clinical safety testing of test items contained in:

• Pharmaceutical products

• Pesticide products

• Cosmetic products

• Veterinary drugs

• Food and feed additives

• Industrial chemicals

What is the Scope of GLP?

Directive 2004/9/EC of The European Commission

• EU Member States shall verify the compliance with GLP of any testing laboratory within their territory claiming to use GLP in the conduct of tests on chemicals.

• Inspection and Audit: The authorities of the EU Member States shall inspect the laboratory and audit the studies in accordance with the provisions laid down in Annex I.

• Annex I, Part A: Guides for compliance monitoring procedures for good laboratory practice.

• Annex I, Part B: Guidance for the conduct of test facility inspections and study audits.

Directive 2004/9/EC of The European Commission

• ___: Guides for compliance monitoring procedures for good laboratory practice.

• ___: Guidance for the conduct of test facility inspections and study audits.

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 on chemical substances.

10 GLP Principles

• Test facility organization and personnel

• Quality Assurance (QA) program

• Facilities

• Apparatus, materials and reagents

• Test systems

• Test and reference items

• Standard Operating Procedures (SOP's)

• Performance of the study

• Reporting of study results

• Storage and retention of records and materials

10 GLP Principles

• Test ___organization and personnel

• Quality ___(QA) program

• Facilities

• Apparatus, materials and ___

• Test ___

• Test and ___items

• Standard ____(SOP's)

• ____of the study

• Reporting of study ____

• ___and ___of records and materials

• Test facility

• Test site

• Test facility management

• Test site management

• Sponsor

• Study director

• Principal investigator

• Quality assurance program

• Standard operating procedures

• Master schedule

• Test facility

• Test site

• Test facility management

• Test site management

• Sponsor

• Study director

• Principal investigator

• Quality assurance program

• Standard operating procedures

• Master schedule

What are the Terms Concerning the Organization of a Test Facility?

• Test ___

• Test ___

• Test ___management

• Test ___management

• ___

• Study ___

• Principal ___

• Quality ___program

• Standard ___

• Master ___

Terms Concerning the Study

• Non-clinical health and environmental safety study

• Short term study

• Study plan

• Study plan amendment

• Study plan deviation

• Test system

• Raw data

• Specimen

• Experimental starting date

• Experimental completion date

• Study initiation date

• Study completion date

Terms Concerning the Study

• ___ health and ____safety study

• ___ term study

• Study ___

• Study plan ___

• Study plan ___

• __system

• __data

• ___

• ___ starting date

• Experimental ___date

• Study ____date

• Study ____date

Test item: the article that is subject of a study

Reference item

Batch

Vehicle

What are the Terms Concerning the Test Item?

The management should ensure that:

• The principles of GLP are complied with

• A sufficient number of qualified personnel, appropriate facilities, equipment and materials are available

• Records of qualifications, job descriptions, training and experience of personnel are maintained

• Personnel understand the functions they are to perform

What are Test Facility Management's Responsibilities? (GLP Principle 1)

The management should ensure that:

• The principles of ___are complied with

• A sufficient number of qualified , appropriate ___, equipment and materials are available

• Records of qualifications, ___descriptions, ___and experience of personnel are maintained

• ___understand the functions they are to perform

• Appropriate and valid SOP's are established and followed

• A Quality Assurance Program is in place

• A Study Director and a Principal Investigator, if needed, is designated

• Documented approval of the study plan

• The study plan is available to quality assurance personnel

What are Test Facility Management's Responsibilities? (GLP Principle 1)

• Appropriate and valid ___are established and followed

• A Quality ___Program is in place

• A Study ___and a Principal ___, if needed, is designated

• Documented approval of the study ___

• The study plan is available to quality ___personnel

• A document control system is in place

• Purchased materials meet specified requirements

• Test and reference items are appropriately characterized

• Clear lines of communication exist

• Computerized systems are suitable for their intended purpose

What are Test Facility Management's Responsibilities? (GLP Principle 1)

• A document ___ system is in place

• Purchased materials meet specified requirements

• Test and ___items are appropriately characterized

• Clear lines of ___exist

• ___ systems are suitable for their intended purpose

• Has the responsibility for the overall performance of the study and the final report

• Approves the study plan and amendments and communicate them to the QA personnel

• Ensures that SOPs, study plans and their amendments are available to study personnel

Study Director's Responsibilities? (GLP Principle 1)

• Has the responsibility for the overall ____of the study and the final report

• Approves the ___plan and amendments and communicate them to the __personnel

• Ensures that ___, study plans and their amendments are available to study personnel

• Ensures that the SOPs are followed, assess the impact of any deviations and takes appropriate corrective and preventive action

• Ensures that: raw data are documented and recorded; computerized systems are validated; SOPs are followed; deviations are acknowledged; records and data are archived

• Sign and date the final report to indicate acceptance of responsibility

Study Director's Responsibilities? (GLP Principle 1)

• Ensures that the ___are followed, assess the impact of any __and takes appropriate corrective and preventive action

• Ensures that: ___ data are documented and recorded; computerized systems are validated; are followed; __ are acknowledged; records and data are archived

• Sign and date the final ___to indicate acceptance of ___

What are Study Personnel Responsibilities? (GLP Principle 1)

• Knowledge of the GLP principals

• Access to the study plan and appropriate SOPs

• Comply with the instructions of the SOPs

• Record raw data

• Study personnel are responsible for the quality of their data

• Exercise health precautions to minimize risk

• Ensure the integrity of the study

What are Study Personnel Responsibilities? (GLP Principle 1)

• Knowledge of the ___principals

• Access to the ___plan and appropriate SOPs

• Comply with the ___of the SOPs

• Record __data

• Study personnel are responsible for the __of their data

• Exercise health ___to minimize risk

• Ensure the __of the study

General Requirements and Responsibilities of the QA Personnel? (GLP Principle 2)

• Documented Quality Assurance (QA) Program

• Designated individuals as members of the QA team directly responsible to the management

• QA members not to be involved in the conduct of the study being assured

• Access to the updated study plans and SOPs

General Requirements and Responsibilities of the QA Personnel? (GLP Principle 2)

• Documented Quality ____ Program

• Designated individuals as members of the QA team directly responsible to the ___

• QA members not to be involved in the conduct of the ___being assured

• Access to the updated study plans and ___

• Documented verification of the compliance of study plan to the GLP principals

• Inspections to determine compliance of the study with GLP principles (Study-based, Facility-based, Process-based)

• Inspection of the final reports for accurate and full description

• Report the inspection results to the management

• Statement

General Requirements and Responsibilities of the QA Personnel? (GLP Principle 2)

• Documented ___of the ___of study plan to the GLP principals

• ___to determine compliance of the study with GLP principles (___-based, ___-based, ___-based)

• Inspection of the final ___for accurate and full description

• Report the inspection results to the ___

• Statement

• Suitable size, construction and location

• Adequate degree of separation of the different activities

• Isolation of test systems and individual projects to protect from biological hazards

• Suitable rooms for the diagnosis, treatment and control of diseases

• Storage rooms for supplies and equipment

Requirements for Facilities? (GLP Principle 3)

• Suitable ___, and _

• Adequate degree of ___of the different activities

• Isolation of test systems and ___projects to protect from ___hazards

• Suitable rooms for the ___, treatment and control of ___

• ___rooms for supplies and equipment

• Separate areas for receipts and storage of the test and reference items

• Separation of test items from test systems

• Archive facilities for easy retrieval of study plans, raw data, final reports, samples of test items and specimen

• Handling and disposal of waste in such a way not to jeopardize the integrity of the study

Requirements for Facilities? (GLP Principle 3)

• Separate areas for ___and storage of the ___and ___items

• Separation of test items from test systems

• Archive ___for easy retrieval of study plans, raw data, final reports, samples of test items and specimen

• ____and disposal of ___in such a way not to jeopardize the integrity of the study

• Apparatus of appropriate design and adequate capacity

• Documented inspection, cleaning, maintenance and calibration of apparatus. Calibration to be traceable to national or international standards

• Apparatus and materials not to interfere with the test systems

• Chemicals, reagent and solutions should be labeled to indicate identity, expiry and specific storage instructions

Requirements for Apparatus, Materials and Reagents? (GLP Principle 4)

• Apparatus of appropriate ___and adequate capacity

• Documented inspection, cleaning, maintenance and calibration of ___. ___to be traceable to national or international standards

• Apparatus and materials not to interfere with the ___systems

• Chemicals, reagent and solutions should be ___to indicate ___, ___and specific storage instructions

• Physical and chemical test systems: Appropriate design and adequate capacity of apparatus used for the generation of data; integrity of physical/chemical test systems

• Biological test systems: Proper conditions for storage, housing, handling and care; isolation of newly received animal and plant test systems until health status is evaluated; humanely destruction of inappropriate test systems

• Records of source, date of arrival, and arrival conditions

Physical/Chemical and Biological Test Systems? (GLP Principle 5)

• _____: Appropriate design and adequate capacity of apparatus used for the generation of data; integrity of physical/chemical test systems

• _____: Proper conditions for storage, housing, handling and care; isolation of newly received animal and plant test systems until health status is evaluated; humanely destruction of inappropriate test systems

• Records of ___, date of ___, and arrival conditions

• Acclimatization of biological systems to the test environment

• Proper identification of test systems in housing/container or when removed

• Cleaning and sanitization of housings or containers

• Pest control agents to be documented; avoid interference from past usage of pesticides

Physical/Chemical and Biological Test Systems? (GLP Principle 5)

• ____of biological systems to the test environment

• Proper ____of test systems in ___ or when removed

• Cleaning and sanitization of ___ or ___

• ___control agents to be documented; avoid ___from past usage of pesticides

• Receipt, handling, sampling and storage: Records for date of receipt, expiry date, quantities received and used; procedures to ensure homogeneity and stability and avoid contamination or mix-up; identification information on storage containers

• Characterization: Identification of each test and reference item (Code, CAS number, name etc.); identification of each batch (Batch number, purity, composition, concentration etc.); cooperation between sponsor and test facility; verification of identity

• Stability: Known stability of test and reference items; stability of the test item in its vehicle (container); experiments to determine stability in tank mixers used in field studies; samples for analytical purposes for each batch

Requirements for Test and Reference Items? (GLP Principle 6)

• ______: Records for date of receipt, expiry date, quantities received and used; procedures to ensure homogeneity and stability and avoid contamination or mix-up; identification information on storage containers

• ______: Identification of each test and reference item (Code, CAS number, name etc.); identification of each batch (Batch number, purity, composition, concentration etc.); cooperation between sponsor and test facility; verification of identity

• ______: Known stability of test and reference items; stability of the test item in its vehicle (container); experiments to determine stability in tank mixers used in field studies; samples for analytical purposes for each batch

• Materials, reagents and solutions: Preparation and labeling

• Record keeping, reporting, storage and retrieval: Coding system, data collection, preparation of reports, indexing system, handling of data

• Test system: Room preparation, environmental conditions, receipt, transfer, identification, preparation, observations

• Quality Assurance Procedures: Operation of QA personnel

Requirements and Categories for Standard Operating Procedures (SOPs)? (GLP Principle 7)

• ____: Preparation and labeling

• ____: Coding system, data collection, preparation of reports, indexing system, handling of data

• ____: Room preparation, environmental conditions, receipt, transfer, identification, preparation, observations

• ____: Operation of QA personnel

• Approved SOPs to ensure quality and integrity of laboratory data; immediately available current SOPs; deviations acknowledged by study director

• Test and reference items: Receipt, identification, labeling, handling, sampling, storage

• Apparatus: Use, maintenance, cleaning, calibration

• Computerized systems: Validation, operation, maintenance, security, change control, back-up

Requirements and Categories for Standard Operating Procedures (SOPs)? (GLP Principle 7)

• Approved ___ to ensure quality and integrity of ____data; immediately available current SOPs; deviations acknowledged by study ___

• ___and ___ items: Receipt, identification, labeling, handling, sampling, storage

• ____: Use, maintenance, cleaning, calibration

• ___ systems: Validation, operation, maintenance, security, change control, back-up

• Study plan: Written plan, verified for GLP compliance, approved by study director and management; approval of amendments by dated signatures; deviations explained and acknowledged

• Content of study plan: Identification of the study (title, nature, purpose, test item, reference item); sponsor and facility info (names and address of sponsor, facility, study director); dates (approval dates, estimated starting/completion dates); reference to test methods; records

• Conduct of the study: Identification of each study; conducted in accordance with study plan; data recorded directly and accurately; changes in raw data not to obscure previous data; identification of electronic data

Required for the Performance of the Study? (GLP Principle 8)

• ____: Written plan, verified for GLP compliance, approved by study director and management; approval of amendments by dated signatures; deviations explained and acknowledged

• ____: Identification of the study (title, nature, purpose, test item, reference item); sponsor and facility info (names and address of sponsor, facility, study director); dates (approval dates, estimated starting/completion dates); reference to test methods; records

• ____: Identification of each study; conducted in accordance with study plan; data recorded directly and accurately; changes in raw data not to obscure previous data; identification of electronic data

• General: Final report for each study; scientists sign and date reports; approval by Study Director; corrections/additions/amendments signed and dated by Study Director

• Content of final report: Identification of study (descriptive title, test/reference item, purity, stability); information on sponsor and facility (names, addresses); experimental starting/completion dates; QA statement; description of materials and test methods; results (uncertainties, level of significance); evaluation discussion and conclusions; storage (samples, reference items, raw data, final reports)

Required for Reporting of Study Results? (GLP Principle 9)

• ___: Final report for each study; scientists sign and date reports; approval by Study Director; corrections/additions/amendments signed and dated by Study Director

• ___: Identification of study (descriptive title, test/reference item, purity, stability); information on sponsor and facility (names, addresses); experimental starting/completion dates; QA statement; description of materials and test methods; results (uncertainties, level of significance); evaluation discussion and conclusions; storage (samples, reference items, raw data, final reports)

• What to retain in archives: Study plan, raw data, samples; inspection data and master schedules; qualification, training experience, job description; maintenance and calibration data; validation data; SOPs; environmental, health & safety monitoring records

• Archive rules: Retention period to be defined; early disposal of study material must be justified and documented; index of materials retained; controlled access

• Laboratory closure: In case the laboratory goes out of business, archives are transferred to the relevant sponsor(s)

Storage and Retention of Records and Materials? (GLP Principle 10)

• ___: Study plan, raw data, samples; inspection data and master schedules; qualification, training experience, job description; maintenance and calibration data; validation data; SOPs; environmental, health & safety monitoring records

• ___: Retention period to be defined; early disposal of study material must be justified and documented; index of materials retained; controlled access

• ___: In case the laboratory goes out of business, archives are transferred to the relevant sponsor(s)