Good laboratory practices as per US FDA, OECD, WHO and Indian GLP. History of GLP GLP guidelines principles of GLP

1. GOOD LABORATORY
PRACTICES
BY
Dr.A.S.CHARAN

2. GOOD PRACTICES (GxP’S)
• GxP is a set of regulations and quality guidelines formulated to ensure
the safety of life sciences products while maintaining the quality of
processes throughout every stage of manufacturing, control, storage,
and distribution.
• The term GxP is a general abbreviation for 'good practice' guidelines
and regulations. The 'x' represents a particular field — clinical (GCP),
manufacturing (GMP), distribution (GDP), laboratory (GLP),
agriculture (GAP), and so on.

4. History of GLP
• The formal, regulatory, concept of “Good Laboratory Practice” (GLP) originated in the USA in the 1970s because of concerns about the
validity of non-clinical safety data submitted to the Food and Drug Administration (FDA) in the context of New Drug Applications (NDA).
• The inspection of studies and test facilities revealed instances of inadequate planning and incompetent execution of studies, insufficient
documentation of methods and results, and even cases of fraud.
• In the chemical and pesticide field, the US Environmental Protection Agency (EPA) had also encountered similar problems with study
quality.
• FDA’s publication of Proposed Regulations on GLP in 1976, with establishment of the Final Rule in June 1979 (21 CFR 58).
• US Environmental Protection Agency (EPA) issued its own draft GLP regulations in 1979 and 1980, publishing the Final Rules in two
separate parts (40 CFR 160 and 40 CFR 792, reflecting their different legal bases) in 1983.
• On the international level, the Organisation for Economic Co-operation and Development (OECD) assembled an expert group to formulate
the first OECD Principles of GLP.
• In 1979 and 1980, an international group of experts established under the Special Programme on the Control of Chemicals developed the
“OECD Principles of Good Laboratory Practice” (GLP).

5. • These Principles of GLP were adopted by the OECD Council in 1981, as an Annex to the
Council Decision on the Mutual Acceptance of Data in the Assessment of Chemicals.
• In 1995 and 1996, a new group of experts was formed to revise and update the Principles.
• Currently OECD PRINCIPLES OF GOOD LABORATORY PRACTICE-1997 are in use.
• The fact that the OECD GLP Principles have acquired wide international acceptance is the
reason why they are used as the reference guide for the WHO/TDR GLP training programme.
• GLP requirements within the European Union (EU) are covered in Section II of the annex to
Council Directive 87/18/EEC, which was amended by Commission Directive 1999/11/EC.
• The UK GLP regulations were published in their latest format as The Good Laboratory Practice
Regulations 1999.
• Indian GLP was framed under Drugs and Cosmetics Act and Rules : Schedule L-I

6. Definition of GLP
• OECD: Good Laboratory Practice (GLP) is a quality system concerned with the
organisational process and the conditions under which non-clinical health and
environmental safety studies are planned, performed, monitored, recorded,
archived and reported.
• US FDA: good laboratory practices for conducting nonclinical laboratory studies
that support or are intended to support applications for research or marketing
permits for products regulated by the Food and Drug Administration, including
food and color additives, animal food additives, human and animal drugs, medical
devices for human use, biological products, and electronic products.

7. Applicability
As far as pharmaceutical development is concerned, the GLP Principles, in their regulatory sense, apply only
to studies which:
• are non-clinical, i.e. mostly studies on animals or in vitro, including the analytical aspects of such studies;
• are designed to obtain data on the properties and/or the safety of items with respect to human health
and/or the environment;
• are intended to be submitted to a national registration authority with the purpose of registering or
licensing the tested substance or any product derived from it.
Depending on national legal situations, the GLP requirements for non-clinical laboratory studies conducted
to evaluate drug safety cover the following classes of studies:
• Single dose toxicity
• Repeated dose toxicity (sub-acute and chronic)
• Reproductive toxicity (fertility, embryo-foetal toxicity and teratogenicity, peri-/post-natal toxicity)
• Mutagenic potential
• Carcinogenic potential
• Toxicokinetics (pharmacokinetic studies which provide systemic exposure data for the above studies)
• Pharmacodynamic studies designed to test the potential for adverse effects (Safety pharmacology)
• Local tolerance studies, including phototoxicity, irritation and sensitisation studies,or testing for suspected
addictive and/or withdrawal effects of drugs

8. OECD PRINCIPLES OF GLP
1. Test Facility Organisation and Personnel: dealing with the management and personnel
issues including job descriptions and training records
1.1. Test Facility Management’s Responsibilities
1.2. Study Director’s Responsibilities
1.3. Principal Investigator’s Responsibilities
1.4. Study Personnel’s Responsibilities
2. Quality Assurance Programme: dealing with the requirement for an independent QA
programme, with personnel who are not involved in the studies, to ensure that GLP is
complied with.
2.1. General
2.2. Responsibilities of the Quality Assurance Personnel
3. Facilities: ensuring that adequate facilities are available to allow the studies to be
carried out without the results being compromised in any way by lack of space or
cross contamination.
3.1. General
3.2. Test System Facilities
3.3. Facilities for Handling Test and Reference Items
3.4. Archive Facilities
3.5. Waste Disposal

9. 4. Apparatus, Material, and Reagents: covering the validation, maintenance and storage of
equipment and chemicals.
5. Test Systems: covering both physicochemical and biological testing systems
5.1. Physical/Chemical
5.2. Biological
6. Test and Reference Items: dealing with the receipt, handling, sampling and storage of all
test and reference materials.
6.1. Receipt, Handling, Sampling and Storage
6.2. Characterisation
7. Standard Operating Procedures: listing the main areas of activity that should be covered
by SOPs, together with the change control requirements for the system.
8. Performance of the Study : dealing with the development of a study plan and also with
its execution.
8.1. Study Plan
8.2. Content of the Study Plan
8.3. Conduct of the Study
9. Reporting of Study Results: the contents and layout of the study report.
9.1. General
9.2. Content of the Final Report
10. Storage and Retention of Records and Materials: dealing with what should be archived
and how those archives should be kept.

10. GLP FOR NONCLINICAL LABORATORY STUDIES-US FDA 21-CFR-58
Subpart A--General Provisions
• § 58.1 - Scope.
• § 58.3 - Definitions.
• § 58.10 - Applicability to studies performed under grants and contracts.
• § 58.15 - Inspection of a testing facility.
Subpart B--Organization and Personnel
• § 58.29 - Personnel.
• § 58.31 - Testing facility management.
• § 58.33 - Study director.
• § 58.35 - Quality assurance unit.
Subpart C--Facilities
• § 58.41 - General.
• § 58.43 - Animal care facilities.
• § 58.45 - Animal supply facilities.
• § 58.47 - Facilities for handling test and control articles.
• § 58.49 - Laboratory operation areas.
• § 58.51 - Specimen and data storage facilities.

11. Subpart D--Equipment
• § 58.61 - Equipment design.
• § 58.63 - Maintenance and calibration of equipment.
Subpart E--Testing Facilities Operation
• § 58.81 - Standard operating procedures.
• § 58.83 - Reagents and solutions.
• § 58.90 - Animal care.
Subpart F--Test and Control Articles
• § 58.105 - Test and control article characterization.
• § 58.107 - Test and control article handling.
• § 58.113 - Mixtures of articles with carriers.
Subpart G--Protocol for and Conduct of a Nonclinical
Laboratory Study
• § 58.120 - Protocol.
• § 58.130 - Conduct of a nonclinical laboratory study.

12. Subparts H-I [Reserved]
Subpart J--Records and Reports
• § 58.185 - Reporting of nonclinical laboratory study results.
• § 58.190 - Storage and retrieval of records and data.
• § 58.195 - Retention of records.
Subpart K--Disqualification of Testing Facilities
• § 58.200 - Purpose.
• § 58.202 - Grounds for disqualification.
• § 58.204 - Notice of and opportunity for hearing on proposed
disqualification.
• § 58.206 - Final order on disqualification.
• § 58.210 - Actions upon disqualification.
• § 58.213 - Public disclosure of information regarding disqualification.
• § 58.215 - Alternative or additional actions to disqualification.
• § 58.217 - Suspension or termination of a testing facility by a sponsor.
• § 58.219 - Reinstatement of a disqualified testing facility.

13. GLP AS PER WHO
1. Resources: Organisation, personnel, facilities and equipment;
2. Characterisation: Test items and test systems;
3. Rules: Protocols, standard operating procedures (SOPs);
4. Results: Raw data, final report and archives;
5. Quality Assurance: Independent monitoring of research processes.

14. GLP AS PER SCHEDULE L-I OF D&C ACT (INDIAN GLP)
1. General Requirements
2. Premises
3. Personnel
4. Equipments
5. Chemicals and Reagents
6. Good house keeping and safety
7. Maintenance, calibration, and validation of equipments
8. Reference materials

15. 9. Microbiological Cultures
10. Quality system
11. Internal quality system audits
12. Management review
13. Standard Operating Procedures
14. Protocols and specifications archive
15. Raw data
16. Storage and archival

16. SUMMARY OF GLP

17. GLP
Describes good practices for non-clinical lab studies that support
research or marketing approvals for FDA-regulated products.
GLP General Requirements
• Appropriately qualified personnel
• Adequate resources
• Appropriate procedures for:
-Sanitation, health precautions, clothing
-Test protocol development, test methods
• -Data analysis, report development
• Appropriately qualified study director
• Quality assurance function
GLP Facilities Requirements
• Suitable size, construction, segregation
-Animal care
-Animal supplies
-Test & control products maintained in a secure area
-Operating “suite”
-Specimen & data storage

18. Equipment Requirements
• Appropriately designed
• Adequate thru-put capacity
• Appropriately located
• Routinely maintained & calibrated
Standard Operating
Procedures
• Animal room prep
• Animal care
• Receipt, ID, storage, handling, mixing & sampling of test &
• control articles
• Test system observations
• Lab tests
• Handling of moribund or dead animals
• Necropsy or postmortem exams of animals
• Collection & ID of specimens
• Histopathology
• Data handling, storage & retrieval
• Equipment maintenance & calibration
• Transfer, proper placement & ID of animals

19. Reagents & Solutions
• Adequate labeling
-Identity
-Concentration
-Storage requirements
-Expiration date
Test & Control Articles
• Adequate characterization
• Proper receipt, storage, distribution
• When mixed with a carrier, adequate methods to confirm
-Mixture uniformity
-Article concentration
-Article stability
Study Implementation
• Written, approved protocol indicating test objectives & methods
• Study conducted in accordance with protocol Study monitoring to
confirm protocol compliance Appropriate labeling of specimens by test
system, study, nature & collection date
• Records of gross findings from postmortems available to pathologist
for specimen histopathology

20. Standard data
capture/recording
requirements
-Legibility
-Permanence
-Accountability
-Changes
Final report of results
Study records & data
methodically archived to
facilitate expedient
retrieval
-Study documents
-Raw data
-Specimens
-Protocols
-QA inspections
-Personnel training & qualifications
-Calibration & maintenance records

21. Records retention
(shortest of):
-≥ 2 yr after FDA marketing clearance
-≥ 5 yr after data submitted to FDA in support of marketing
application
-≥ 2 yr after Sponsor decision not to proceed with marketing
application
-Wet specimens hold as long as viable
Records transferable with written FDA notification
Facility Disqualification
Grounds for disqualification:
-Failure to comply with regulations &
-Noncompliance adversely affects study validity &
-Previous regulatory actions have been unsuccessful in
modifying facility operations

22. THANK YOU