The document discusses Good Laboratory Practices (GLP). It provides definitions and history of GLP. GLP refers to a quality management system for laboratories conducting non-clinical safety studies. It aims to ensure reliability and integrity of test data. Key aspects of GLP include organization, SOPs, facilities, equipment, test systems, study planning and reporting, archiving. Non-compliance can result in disqualification and rejection of study data by regulatory agencies.

1. Good Laboratory Practices (GLP)
Dr Ravi Kant Agrawal, MVSc, PhD
Senior Scientist (Veterinary Microbiology)
Food Microbiology Laboratory
Division of Livestock Products Technology
ICAR-Indian Veterinary Research Institute
Izatnagar 243122 (UP) India

2. GLP: GOOD LABORATORY PRACTICE
• The phrase Good Laboratory Practice or GLP specifically
refers to a quality system of management controls for
research laboratories and organizations to ensure the
uniformity, consistency, reliability, reproducibility,
quality, and integrity of chemical (including
pharmaceuticals) non-clinical safety tests; from physio-
chemical properties through acute to chronic toxicity
tests.
• Medicines and Healthcare products Regulatory Agency-
UK which defines GLP as: “Good Laboratory Practice
(GLP) embodies a set of principles that provides a
framework within which laboratory studies are planned,
performed, monitored, recorded, reported and
archived”.
• GOOD LABORATORY PRACTICE applies to non-clinical
studies conducted for the assessment of the safety or
efficacy of chemicals (including pharmaceuticals).
• GLP, a data quality system, should not be confused
with standards for laboratory safety – appropriate
gloves, glasses & clothing to handle lab materials
safely.

3. GLP
• An internationally recognized definition of GLP:
“Good Laboratory Practice (GLP) embodies a set of principles
that provides a framework within which laboratory studies are
planned, performed, monitored, recorded, reported and
archived”.
 These studies are undertaken to generate data by which the
hazards and risks to users, consumers and third parties,
including the environment, can be assessed for pharmaceuticals
(only preclinical studies), agrochemicals, cosmetics, food
additives, feed additives and contaminants, novel foods,
biocides, detergents etc.
 GLP helps assure regulatory authorities that the data submitted
are a true reflection of the results obtained during the study and
can therefore be relied upon when making risk/safety
assessments.
 GLP is an FDA regulation.

4. HISTORY
• The term GLP was first used in New Zealand in 1972.
• GLP was first introduced in New Zealand and Denmark in 1972, and later
in the US in 1978 in response to the Industrial BioTest Labs scandal.
• GLP is a formal regulation that was created by the US FDA (United states
food and drug administration) in 1978.
• GLP was instituted in US following cases of fraud generated by
toxicology labs in data submitted to the FDA by pharmaceutical
companies. As a result of these findings, FDA promulgated the Good
Laboratory Practice (GLP) Regulations, 21 CFR part 58, on December 22,
1978 (43 FR 59986). The regulations became effective June 1979.
• Assure the quality and integrity of safety Nonclinical laboratory studies
• Although GLP originated in the United States, it had a world wide
impact.
• Non-US companies that wanted to do business with the United states or
register their pharmacies in the United States had to comply with the
United States GLP regulations.
• They eventually started making GLP regulations in their home countries.
• CFR: Code of Federal regulations

5. HISTORY
• In 1981 an organization named OECD (Organization for
Economic Co-operation and Development) produced GLP
principles that are international standard.
• OECD has since helped promulgate GLP to many countries.
• Following Decision C(97),186/Final of the OECD Council, data
generated in the testing of chemicals in one OECD Member
Country, in accordance with OECD Test Guidelines and the
Principles of GLP are accepted in all other OECD Member
Countries. OECD: ENV/MC/CHEM(98)17 part two
• GLP is a quality system concerned with the organizational
process and conditions under which non-clinical health and
environmental safety studies are planned, performed,
monitored, recorded, archived and reported.[5]

6. 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.

7. FAMOUS EXAMPLE
• One of the labs that went under
such an investigation made
headline news.
• The name of the Lab was
Industrial Bio Test. This was a big
lab that ran tests for big
companies such as Procter and
Gamble.
• It was discovered that mice that
they had used to test cosmetics
such as lotion and deodorants
had developed cancer and died.
• Industrial Bio Test lab threw the
dead mice and covered results
deeming the products good for
human consumption.
• Those involved in production,
distribution and sales for the lab
eventually served jail time.

8. 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.

9. GLP Principles
1. Organization and Personnel
 Management-Responsibilities
 Sponsor-Responsibilities
 Study Director-Responsibilities
 Principal Investigator-Responsibilities
 Study Personnel-Responsibilities
2. Quality assurance program
 Quality Assurance Personnel
3. Facilities
 Test System Facilities
 Facilities for Test and Reference Items
4. Equipment, reagents and Materials
5. Test systems
 Physical/Chemical
 Biological
6. Test & Reference items
7. Standard operating procedures
8. Performance of Study
 Study Plan
 Conduct of Study
9. Reporting of results
10. Archival - Storage of Records and Reports

10. Basic elements in GLP
• Personnel
 Sponsor
 Management
 Study director
 Quality Assurance
• Facility
 Laboratory
Operation
 Animal care
 Equipment
 Reagents
 Storage
10
• Documents
 Standard Operating Protocols
 Reports
 Archiving
• Test and Control Articles
 Characterization
 Handling
 Storage

11. Personnel
• Qualification of personnel:
The assumptions is that in order to conduct GLP studies with right
quality a couple of things are important;
1)There should be sufficient number.
2)The personnel should be qualified.
• Sponsor:
Sponsor: person who initiates and supports non-clinical laboratory
study, a person who submits non-clinical study to FDA or testing
facility that initiates and conducts the study.
• Facility management:
Responsibilities of facility management is well defined. They
designate a study director, as well as assure quality assurance unit
is available, test and control articles are characterized.
12/10/18 11

12. • Study director:
He has overall responsibilities for technical conduct
safety studies, as well as interpretation, analysis,
documentation and reporting of results.
• Quality Assurance unit:
The quality assurance unit (QAU) serves an internal
control function. It is responsible for monitoring each
study to assure management that facilities, equipment,
personnel, methods, practices, records, controls, SOPs,
final reports (for data integrity), and archives are in
conformance with the GLP/GALP
12/10/18 12

13. Instrumentation Validation
• This is a process necessary for any analytical laboratory.
• Data produced by “faulty” instruments may give the
appearance of valid data.
• Equipment shall be adequately inspected, cleaned & maintained
• Equipment used for assessment of data shall be tested,
calibrated and/or standardized
• Scales & balances should be calibrated at regular intervals
(usually ranging from 1-12 months)
• The frequency for calibration, re-validation and testing depends
on the instrument and extent of its use in the laboratory.
• Whenever an instrument’s performance is outside the “control
limits” reports must be discontinued.
• Equipment records should include:
Name of the equipment and manufacturer
Model or type for identification
Serial number
Date equipment was received in the laboratory
Copy of manufacturers operating instruction (s)

14. Important questions to be answered for any
analytical instrument
• What is the equipment being used for?
• Is the instrument within specification and is the
documentation to prove this available?
• If the instrument is not within specifications, how much
does it deviate by?
• If the instrument is not within specifications what action
has been taken to overcome the defect?
• Can the standards used to test and calibrate the
instrument be traced back to national standards?

15. Reagent/ Materials Certification
 This policy is to assure that reagents used are specified
in the standard operating procedure.
 Purchasing and testing should be handled by a quality
assurance program.
Requirements:
 Reagents and solutions shall be labeled
 Deteriorated or outdated reagents and solutions shall
not be used
 Include Date opened
 Stored under ambient temperature
 Expiration date
12/10/18 15

16. Documents: Standard Operating Procedures
(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
12/10/18 16

17. Statistical Procedures for Data
Evaluation Statistical procedures are not simply chosen from a text
book
 Practitioners in a particular field may adopt certain
standards which are deemed acceptable within that
field.
 Regulatory agencies often describe acceptable
statistical procedures.
12/10/18 17

18. Test and control articles
• Control articles or reference substances as they re-
called in the OECD principles are of utmost importance
as they are commonly used to calibrate the instrument.
• Main requirements for control articles are: the identity,
strength, purity, composition and other characteristics
should be determined for each batch and documented.
• The stability of each test and articles should also be
determined.
• Certified reference standards can be purchased from
appropriate suppliers. If standards are not available , the
recommendation is to take a lot of your own material and
analyze, certify and use it as the standard.
12/10/18 18

19. Analyst Certification
 Some acceptable proof of satisfactory training and/or
competence with specific laboratory procedures must be
established for each analyst.
 Qualification can come from education, experience or
additional trainings, but it should be documented
 Sufficient people
 Requirements of certification vary
12/10/18 19

20. Laboratory Certification
 Normally done by an external agency
 Evaluation is concerned with issues such as
 Adequate space
 Ventilation
 Storage
 Hygiene
12/10/18 20

21. Documentation and Maintenance of
Records
 Maintenance of all records provide documentation
which may be required in the event of legal challenges
due to repercussions of decisions based on the original
analytical results.
 General guidelines followed in regulated laboratories is
to maintain records for at least five years
 Length of time over which laboratory records should be
maintained will vary with the situation
12/10/18 21

22. Specimen/Sample Tracking
• Vary among laboratories
• Must maintain the un-mistakable connection between a
set of analytical data and the specimen and/or samples
from which they were obtained.
• Original source of specimen/sample(s) must be recorded
and unmistakably connected with the set of analytical
data.

23. What happens if a workplace does
not comply with federal/National
Good Laboratory Practice
standards?
National Accreditation Board for
Testing and Calibration
Laboratories
(NABL)

24. Disqualification of a Facility
• Before a workplace can experience the consequences of
non-compliance, an explanation of disqualification is
needed
• The FDA states the purpose of disqualification as the
exclusion of a testing facility from completing laboratory
studies or starting any new studies due to not following
the standards of compliance set by the Good Laboratory
Practice manual.

25. Possible Violations
• Falsifying information for permit, registration or any
required records.
• Falsifying information related to testing ~ protocols,
ingredients, observations, data equipment etc.
• Failure to prepare, retain, or submit written records
required by law.

26. Grounds for Disqualification
• The testing facility failed to comply with one or more
regulations implemented by the GLP manual.
• The failure to comply led to adverse outcomes in the
data; in other words, it affected the validity of the
study.
• Warnings or rejection of previous studies have not
been adequate to improve the facility’s compliance.

27. Consequences of Noncompliance
• The FDA states the following consequences of
noncompliance:
– The commissioner will send a written proposal of
disqualification to the testing facility
– A regulatory hearing on the disqualification will be
scheduled
– If the commissioner finds that after the hearing, the
facility has complied, then a written statement with
an explanation of termination of disqualification will
be sent to the facility
– Thus, if it can be shown that such disqualifications
did not affect the integrity and outcome of the study
itself, or did not occur at all, then the study may be
reinstated at the will of the commissioner

28. Upon Disqualification…
• If the commissioner finds that the facility was non-
compliant on any of the grounds after the hearing,
then a final order of non-compliance will be sent to
the facility with explanations
• If a testing facility has been disqualified, any studies
done before of after the disqualification will need to be
determined as essential to a decision (acceptable or
not)
• If the study is determined unacceptable, then the facility
itself may need to show that the study was not affected
by the non-compliance that led to the disqualification
• Once finally disqualified, the facility may not receive or
be considered for a research or marketing permit and
the study is rejected.

29. Upon Disqualification…
• The commissioner may notify the public and all interested persons,
including other federal agencies the facility may have contacted
• The FDA may ask the other agencies to consider whether to
support the facility or not under the disqualification
• Civil or criminal proceedings may occur at the discretion of the
commissioner
– Fines of up to $50,000 if one knowingly commits crime and/or 1
year imprisonment~ for registration applicants and producers
– Fines up to $5,000 all others~ civil penalty after failing to
improve after a minor violation warning was issued~ only those
involved in testing will be given civil penalties
– Those involved in the distribution or sales will be assessed
more heavy penalties, such as criminal penalties
• The FDA may turn it over to the federal, state or local law
enforcement
• The facility’s sponsor may terminate or suspend the facility from
doing any non- clinical study for a permit
• The sponsor is required to notify the FDA in writing within 15
working days that the facility is to be suspended or terminated and
why

30. Reinstatement of a Disqualified Facility
• The testing facility may be reinstated as acceptable non-clinical
study to be turned into the FDA if the commissioner can be certain
that future studies will be conducted in compliance with the Good
Laboratory Practice standards and that any current studies
integrity have not been severely harmed by the disqualification
• The disqualified facility will be required to put in writing to the
commissioner reasons why it should be reinstated and any actions
the facility will take or have taken to assure any disqualification
problems will not happen again.
• The commissioner will inspect the facility and determine if it shall
be reinstated
• If it is reinstated, the commissioner is required to notify all persons
that were notified of the disqualification including the facility itself

31. References
 http://www.sjsu.edu/faculty/chem55/55glpout.htm
 http://www.labcompliance.com/tutorial/glp/default.aspx?
sm=d_a
 UGA Office of the Vice President for Research
 Wikipedia

32. Thanks
Acknowledgement: All the material/presentations available online on
the subject are duly acknowledged.
Disclaimer: The author bear no responsibility with regard to the source
and authenticity of the content.
Questions???