2. GOOD LABORATORY PRACTICE
In the experimental (non-clinical) research arena, Good
laboratory practice or GLP is a quality system of management
controls for research laboratories and organizations to ensure
the uniformity, consistency, reliability, reproducibility, quality, and
integrity of products in development for human or animal health
(including pharmaceuticals) through non-clinical safety tests,
from physio-chemical properties through acute to chronic
toxicity tests.
3. HISTORY
In response to malpractice in research and development activities
by pharmaceutical companies and contract facilities used by
them.
The malpractice included cases of fraud, lack of proper
management and organization of studies performed to generate
data for regulatory dossiers.
GLP first came in to enforce in USA due to some fraud data
generated by toxicology lab to FDA.
Industrial Bio Test Labs (IBT) was the most notable cases,
where thousands of safety test for chemical manufactures were
falsely claimed to have been performed or were so poor. (Test
carried for lotion and deodorant – cancer)
4. WHY WAS GLP CREATED?
In the early 70’s FDA became aware of cases of poor laboratory
practice all over the United States.
FDA decided to do an in-depth investigation on 40 toxicology labs.
They discovered a lot fraudulent activities and a lot of poor lab
practices.
Examples of some of these poor lab practices found were
1. Equipment not been calibrated to standard form , therefore
giving wrong measurements.
2. Incorrect/inaccurate accounts of the actual lab study
3. Inadequate test systems
5. OBJECTIVES OF GLP
GLP makes sure that the data submitted are a true reflection
of the results that are obtained during the study.
GLP also makes sure that data is traceable.
Promotes international acceptance of tests.
To ensure and promote safety, consistency, high quality,
and reliability of chemicals in the process of non-clinical
and laboratory testing.
6. MISSION OF GLP
Archiving of records and
materials.
Apparatus, material and
reagent facilities.
Quality assurance programs.
Performance of the study.
Reporting of study results.
Standard operating procedures
(SOP)
Personnel and test facility
organization
7. GLP MAINLY GIVES STRESS
ON FIVE POINTS:
Resources: organization, personnel, facilities & equipment.
Characterization: Test items and test system.
Rules: Study plans(or protocol) and written procedure.
Results: Raw data, final report and archives.
Quality Assurance.
8. PRINCIPLE OF GLP
Test Facility Organization and Personnel
Quality Assurance of Programme
Facilities
Apparatus, Material, and Reagents
Test Systems
Test and Reference Items
Performance of the study results
Reporting of Study results
Storage and Retention of Records and Materials
9. TEST FACILITY ORGANIZATION
AND PERSONNEL
Test Management’s Responsibilities
Study Director’s Responsibilities
Study Principal Investigator’s Responsibilities
Study Personnel’s Responsibilities
10. A. TEST MANAGEMENT’S
RESPONSIBILITIES
Sufficient number of qualified personnel,
appropriate facilities, equipment, and materials
are available for the timely and proper conduct
of the study.
Ensure the maintenance of a record of the qualifications, training,
experience.
Job description for each professional and technical individual.
Documented approval of the study plan by the study director.
11. B. STUDY DIRECTOR’S
RESPONSIBILITIES
Approve the study plan.
Any amendments to the study plan by dated signature.
Availability of SOPS to the personnel.
Raw data generated are fully documented and recorded.
12. C. PRINCIPAL
INVESTIGATOR’S
RESPONSIBILITIES
The Principal Investigator will ensure that the delegated phases of
the study are conducted in accordance with the applicable
principles of Good Laboratory Practice.
Execute the plan of work as per GLP.
Management of Research: Integrity
Design
Conducting
Reporting
14. 2. QUALITY ASSURANCE
PROGRAM
The purpose of quality assurance program is to assure that all
laboratory testing is performed according to the principles of
current GLP.
This is carried out by the quality assurance department which
has authority to authorize all the quality related
documentation.
The quality assurance department is staffed by individuals
who are knowledgeable of, and familiar with the laboratory
testing.
15. RESPONSIBILITIES OF QUALITY
ASSURANCE PERSONNEL
Maintain all approved study plan & SOPs have access to
up-date copy of Master Schedule.
Verify the study plan contains the information require for
compliance with principle of GLP(Verification should be
documented.)
QA personnel must be independent from scientists
involved in the operational aspects of the study being
performed.
16. 3. FACILITIES
A. TEST SYSTEM FACILITY:
Sufficient number of rooms or areas assure the isolation of test
system & the isolation of individual projects involving substance
or organisms known to be or suspected of being bio-hazardous.
There should be storage rooms or areas as needed for supplies &
equipment.
Area should be available for the diagnosis, treatment & control
of disease, in order to ensure that there is no unacceptable degree
of deterioration of test system.
17. B. ARCHIVE FACILITY:
Archive facilities should be provided for the secure storage &
retrieval of study plans raw data, final report, samples of the test
items and specimens.
Archive design & archive conditions should be protect contents
from untimely deterioration.
C. WASTE DISPOSAL
Handling disposal of wastes should be carried out in such a way as
not to the integrity of studies.
This includes provision for appropriate collection, storage &
disposal facilities & decontamination & transportation procedures.
18. 4. APPARATUS, MATERIAL,
REAGENTS
A. APPARATUS:
Apparatus, including validated computerized system, used
for the generation, storage & retrieval of data, & for
controlling environmental factors relevant to the study.
Apparatus used in a study should be periodically inspected,
cleaned, maintained, & calibrated acc. to SOP.
Equipment record should be maintained:- Name, Mode,
Serial no., Date of received & Manufacturing Operating
Instructions.
19. APPARATUS, MATERIAL,
REAGENTS CON...
B. MATERIAL & REAGENT:
Chemicals, reagents & solutions should be labelled to indicate Identity
(with conc. if appropriate)
Expiry date & specific storage instructions.
Information concerning source, preparation date & stability shoud be
available.
The expiry date may be extended on the basis of documented
evaluation or analysis.
Date ofopening should be mentioned.
Purchase & testing should be handled by an QA personnel.
21. 6. TEST SYSTEM & REFERENCE ITEMS
The test system could be animal, aplant, a baterium, an isolated
organ, a field or other ecosystem or even analytical equipments, etc.
Physical & Chemical Test Sytems:
Appropriate design and adequate capacity of apparatus used for the
generation of data.
Integrity of physical/chemical test system.
Biological Test System:
Proper conditions for storage, housing, handling, & care.
Isolation of newly received animal & plant test system until health
status is evaluated.
Humanely destruction of inappropriate test system.
22. 7. PERFORMANCE
OF THE STUDY
Study Plan
Content of the Study Plan
Dates
Test Methods
Issues (where applicable)
Records
A lis of records to be retained.
Conduct of the study
23. RULES
Rules for organizing & conducting GLP studies must be defined in
documents approved by management.
Rules defining who does what, how, when, and where, are called
prescriptive document.
2 Main Types of Prescriptive Documents:
1. The Protocol(or study plan): The protocol is a high level
document which defines the study design.
2. Standard Operating Procedures (SOP): SOPs are instructions on
hw to perform the routine procedures that make up a good part of th
study.
24. STANDARD OPERATION
PROCEDURE (SOP)
Written procedures for a laboratories program.
They define how to carry out protocol-specified activities.
Most often written in a chronological listing of action steps.
They are written to explain how the procedures are suppose to
work.
Routine inspection, cleaning, maintenance, testing and
calibration.
Actions to be taken in response to equipment failure.
Analytical methods
Definition of raw data
Keeping records, reporting, storage, mixing, and retrieval of
data
25. 8. REPORTING OF STUDY
RESULTS
Name and address of test facility.
Date of start and finish of the study.
Name of the study Director.
Objectives of the study.
Details of the test system.
Prescription of the test system.
Details of dosing, route, & duration.
Summary of findings.
Discussion.
Conclusion.
References.
26. Final report should be signed by study Director.
Once its been signed, it cannot be changed.
The amendment must indicate what is being changed or added
to the report & why the modification is being made.
The amendment must be signed by the study director and
must be audited by the QAU (Quality Assurance Unit).
27. 9. STORAGE & RETENTION
OF RECORDS & MATERIAL
The study plan, raw data, samples of test & reference items,
specimens and final report of each study.
Records of all inspections prformed by the QA program, as
well a master schedule.
Records of qualifications, training, experience and job
descriptions of personel.
Records & reports of the maintenance & calibration of
apparatus
Validation documentation for computerized systems.
28. ARCHIVES
Archives is not a simple place for storage of old materials.
Safe depository of invaluable information.
What is left at the end of the study is usd to demonstrate the validity
& traceability of the scientific results.
FUNCTION:
Long term, secure storage &
fast retrieval of data
Contains all original scientific
data, master documents reports,
endpoint of regulated work.
SECURITY:
Only authorized entry permited-
as per SOP.
Protection agaist fire, flood and
vandalism if possible.
29. DISQUALIFICATION OF A
FACILITY
Before a workplace can experience the consequences of
noncompliance, an explanation of dis qualification is needed.
The FDA states the purpose of disqualification as the exclusion of a
testing facility from completing laboratory studies or atarting any
new studies due to not following the standards of compiance set by
the GLP manual.
POSSIBLE VIOLATIONS:
Falsifying information for permit, registration, or any required
records.
Falsifying information related to testing protocols, ingredients,
observations, data equipments etc.
Failure to prepare, retain, or submit written records reuired by law.
30. CONSEQUENCES OF NONCOMPLIANCE
The FDA states the following consequences of noncompliance:
The commissioner will send a proposal of disqualification written to
the testing facility.
A regulatory hearing on the disqualification will be scheduled.
If the commisioner finds that after hearing. the facility has complied,
then a written statement with an explation of termination of
disqualification will be sent to the facility.
Oncefinally disqualified, the facility may not recieve or be
considered for a research or marketing
permit and the study is rejected.
The commissioner may notify the public and all intrested person,
including other fedearl agencies the facility may have contacted.
