1. Good Laboratory PracticesGood Laboratory Practices
Lori GladneyLori Gladney
Izabella OsakweIzabella Osakwe
Endia FordEndia Ford
2. GLP: GOOD LABORATORYGLP: GOOD LABORATORY
PRACTICEPRACTICE
GLPGLP is an FDA regulation.is an FDA regulation.
DefinitionDefinition: GLP: GLP
embodies a set ofembodies a set of
principles that provides aprinciples that provides a
framework within whichframework within which
laboratory studies arelaboratory studies are
planned performed,planned performed,
monitored, reported andmonitored, reported and
archived.archived.
GLP is sometimesGLP is sometimes
confused with theconfused with the
standards of laboratorystandards of laboratory
safety like wearing safetysafety like wearing safety
goggles.goggles.
3. HISTORYHISTORY
GLP is a formal regulation that was created by theGLP is a formal regulation that was created by the
FDA (United states food and drug administration) inFDA (United states food and drug administration) in
1978.1978.
Although GLP originated in the United States , it hadAlthough GLP originated in the United States , it had
a world wide impact.a world wide impact.
Non-US companies that wanted to do business withNon-US companies that wanted to do business with
the United states or register their pharmacies in thethe United states or register their pharmacies in the
United States had to comply with the United StatesUnited States had to comply with the United States
GLP regulations.GLP regulations.
They eventually started making GLP regulations inThey eventually started making GLP regulations in
their home countries.their home countries.
In 1981 an organization named OECD (organizationIn 1981 an organization named OECD (organization
for economic co-operation and development )for economic co-operation and development )
produced GLP principles that are internationalproduced GLP principles that are international
standard.standard.
4. WHY WAS GLP CREATED?WHY WAS GLP CREATED?
In the early 70’s FDA becameIn the early 70’s FDA became
aware of cases of poor laboratoryaware of cases of poor laboratory
practice all over the United States.practice all over the United States.
FDA decided to do an in-depthFDA decided to do an in-depth
investigation on 40 toxicologyinvestigation on 40 toxicology
labs.labs.
They discovered a lot fraudulentThey discovered a lot fraudulent
activities and a lot of poor labactivities and a lot of poor lab
practices.practices.
Examples of some of these poorExamples of some of these poor
lab practices found werelab practices found were
1.1. Equipment not been calibrated toEquipment not been calibrated to
standard form , therefore givingstandard form , therefore giving
wrong measurements.wrong measurements.
2.2. Incorrect/inaccurate accounts ofIncorrect/inaccurate accounts of
the actual lab studythe actual lab study
3.3. Inadequate test systemsInadequate test systems
5. FAMOUS EXAMPLEFAMOUS EXAMPLE
One of the labs that wentOne of the labs that went
under such an investigationunder such an investigation
made headline news.made headline news.
The name of the Lab wasThe name of the Lab was
Industrial Bio Test. This was aIndustrial Bio Test. This was a
big lab that ran tests for bigbig lab that ran tests for big
companies such as Proctercompanies such as Procter
and Gamble.and Gamble.
It was discovered that miceIt was discovered that mice
that they had used to testthat they had used to test
cosmetics such as lotion andcosmetics such as lotion and
deodorants had developeddeodorants had developed
cancer and died.cancer and died.
Industrial Bio Test lab threwIndustrial Bio Test lab threw
the dead mice and coveredthe dead mice and covered
results deeming the productsresults deeming the products
good for human consumption.good for human consumption.
Those involved in production,Those involved in production,
distribution and sales for thedistribution and sales for the
lab eventually served jail time.lab eventually served jail time.
6. OBJECTIVES OF GLPOBJECTIVES OF GLP
GLP makes sure that the data submittedGLP makes sure that the data submitted
are a true reflection of the results that areare a true reflection of the results that are
obtained during the study.obtained during the study.
GLP also makes sure that data isGLP also makes sure that data is
traceable.traceable.
Promotes international acceptance ofPromotes international acceptance of
tests.tests.
7. MISSION OF GLPMISSION OF GLP
Test systemsTest systems
Archiving of records and materials.Archiving of records and materials.
Apparatus, material and reagent facilities.Apparatus, material and reagent facilities.
Quality assurance programs.Quality assurance programs.
Performance of the study.Performance of the study.
Reporting of study results.Reporting of study results.
Standard operating procedures (SOP)Standard operating procedures (SOP)
Personnel and test facility organizationPersonnel and test facility organization
8. Standard Operating ProceduresStandard Operating Procedures
(SOP)(SOP)
Written procedures for a laboratoriesWritten procedures for a laboratories
program.program.
They define how to carry out protocol-They define how to carry out protocol-
specified activities.specified activities.
Most often written in a chronological listingMost often written in a chronological listing
of action steps.of action steps.
They are written to explain how theThey are written to explain how the
procedures are suppose to workprocedures are suppose to work
9. SOPSOP
Routine inspection, cleaning,Routine inspection, cleaning,
maintenance, testing and calibration.maintenance, testing and calibration.
Actions to be taken in response toActions to be taken in response to
equipment failure.equipment failure.
Analytical methodsAnalytical methods
Definition of raw dataDefinition of raw data
Keeping records, reporting, storage,Keeping records, reporting, storage,
mixing, and retrieval of datamixing, and retrieval of data
10. Statistical Procedures for DataStatistical Procedures for Data
EvaluationEvaluation
Statistical procedures are not simplyStatistical procedures are not simply
chosen from a text bookchosen from a text book
Practitioners in a particular field may adoptPractitioners in a particular field may adopt
certain standards which are deemedcertain standards which are deemed
acceptable within that field.acceptable within that field.
Regulatory agencies often describeRegulatory agencies often describe
acceptable statistical procedures.acceptable statistical procedures.
11. Instrumentation ValidationInstrumentation Validation
This is a process necessary for anyThis is a process necessary for any
analytical laboratory.analytical laboratory.
Data produced by “faulty” instruments mayData produced by “faulty” instruments may
give the appearance of valid data.give the appearance of valid data.
The frequency for calibration, re-validationThe frequency for calibration, re-validation
and testing depends on the instrumentand testing depends on the instrument
and extent of its use in the laboratory.and extent of its use in the laboratory.
Whenever an instrument’s performance isWhenever an instrument’s performance is
outside the “control limits” reports must beoutside the “control limits” reports must be
discontinueddiscontinued
12. Instrument Validation (cont)Instrument Validation (cont)
Equipment records should include:Equipment records should include:
Name of the equipment and manufacturerName of the equipment and manufacturer
Model or type for identificationModel or type for identification
Serial numberSerial number
Date equipment was received in theDate equipment was received in the
laboratorylaboratory
Copy of manufacturers operatingCopy of manufacturers operating
instruction (s)instruction (s)
13. Reagent/ Materials CertificationReagent/ Materials Certification
This policy is to assure that reagents usedThis policy is to assure that reagents used
are specified in the standard operatingare specified in the standard operating
procedure.procedure.
Purchasing and testing should be handledPurchasing and testing should be handled
by a quality assurance program.by a quality assurance program.
14. Reagents and Solutions contReagents and Solutions cont
Requirements:Requirements:
Reagents and solutions shall be labeledReagents and solutions shall be labeled
Deteriorated or outdated reagents andDeteriorated or outdated reagents and
solutions shall not be usedsolutions shall not be used
Include Date openedInclude Date opened
Stored under ambient temperatureStored under ambient temperature
Expiration dateExpiration date
15. Analyst CertificationAnalyst Certification
Some acceptable proof of satisfactorySome acceptable proof of satisfactory
training and/or competence with specifictraining and/or competence with specific
laboratory procedures must belaboratory procedures must be
established for each analyst.established for each analyst.
Qualification can come from education,Qualification can come from education,
experience or additional trainings, but itexperience or additional trainings, but it
should be documentedshould be documented
Sufficient peopleSufficient people
Requirements of certification varyRequirements of certification vary
16. Laboratory CertificationLaboratory Certification
Normally done by an external agencyNormally done by an external agency
Evaluation is concerned with issues such asEvaluation is concerned with issues such as
Adequate spaceAdequate space
VentilationVentilation
StorageStorage
HygieneHygiene
17. Specimen/Sample TrackingSpecimen/Sample Tracking
Vary among laboratoriesVary among laboratories
Must maintain the unmistakableMust maintain the unmistakable
connection between a set of analyticalconnection between a set of analytical
data and the specimen and/or samplesdata and the specimen and/or samples
from which they were obtained.from which they were obtained.
Original source of specimen/sample (s)Original source of specimen/sample (s)
must be recorded and unmistakablymust be recorded and unmistakably
connected with the set of analytical data.connected with the set of analytical data.
18. Documentation and Maintenance ofDocumentation and Maintenance of
RecordsRecords
Maintenance of all records provideMaintenance of all records provide
documentation which may be required in thedocumentation which may be required in the
event of legal challenges due to repercussionsevent of legal challenges due to repercussions
of decisions based on the original analyticalof decisions based on the original analytical
results.results.
General guidelines followed in regulatedGeneral guidelines followed in regulated
laboratories is to maintain records for at leastlaboratories is to maintain records for at least
five yearsfive years
Length of time over which laboratory recordsLength of time over which laboratory records
should be maintained will vary with the situationshould be maintained will vary with the situation
19. Important questions to be answered for anyImportant questions to be answered for any
analytical instrumentanalytical instrument
What is the equipment being used for?What is the equipment being used for?
Is the instrument within specification and is theIs the instrument within specification and is the
documentation to prove this available?documentation to prove this available?
If the instrument is not within specifications, howIf the instrument is not within specifications, how
much does it deviate by?much does it deviate by?
If the instrument is not within specifications whatIf the instrument is not within specifications what
action has been taken to overcome the defect?action has been taken to overcome the defect?
Can the standards used to test and calibrate theCan the standards used to test and calibrate the
instrument be traced back to national standards?instrument be traced back to national standards?
20. What happens if a workplaceWhat happens if a workplace
does not comply with federaldoes not comply with federal
Good Laboratory PracticeGood Laboratory Practice
standards?standards?
21. Disqualification of a FacilityDisqualification of a Facility
Before a workplace can experience theBefore a workplace can experience the
consequences of noncompliance, anconsequences of noncompliance, an
explanation of disqualification is neededexplanation of disqualification is needed
The FDA states the purpose ofThe FDA states the purpose of
disqualification as the exclusion of adisqualification as the exclusion of a
testing facility from completing laboratorytesting facility from completing laboratory
studies or starting any new studies due tostudies or starting any new studies due to
not following the standards of compliancenot following the standards of compliance
set by the Good Laboratory Practiceset by the Good Laboratory Practice
manualmanual
22. Possible ViolationsPossible Violations
Falsifying information for permit,Falsifying information for permit,
registration or any required recordsregistration or any required records
Falsifying information related to testing~Falsifying information related to testing~
protocols, ingredients, observations, dataprotocols, ingredients, observations, data
equipment, ect.equipment, ect.
Failure to prepare, retain, or submit writtenFailure to prepare, retain, or submit written
records required by lawrecords required by law
23. Grounds for DisqualificationGrounds for Disqualification
The testing facility failed to comply withThe testing facility failed to comply with
one or more regulations implemented byone or more regulations implemented by
the GLP manualthe GLP manual
The failure to comply led to adverseThe failure to comply led to adverse
outcomes in the data; in other words, itoutcomes in the data; in other words, it
affected the validity of the studyaffected the validity of the study
Warnings or rejection of previous studiesWarnings or rejection of previous studies
have not been adequate to improve thehave not been adequate to improve the
facility’s compliancefacility’s compliance
24. Consequences of NoncomplianceConsequences of Noncompliance
The FDA states the following consequences ofThe FDA states the following consequences of
noncompliance:noncompliance:
The commissioner will send a written proposal ofThe commissioner will send a written proposal of
disqualification to the testing facilitydisqualification to the testing facility
A regulatory hearing on the disqualification will beA regulatory hearing on the disqualification will be
scheduledscheduled
If the commissioner finds that after the hearing, theIf the commissioner finds that after the hearing, the
facility has complied, then a written statement with anfacility has complied, then a written statement with an
explanation of termination of disqualification will beexplanation of termination of disqualification will be
sent to the facilitysent to the facility
Thus, if it can be shown that such disqualifications didThus, if it can be shown that such disqualifications did
not affect the integrity and outcome of the study itself,not affect the integrity and outcome of the study itself,
or did not occur at all, then the study may beor did not occur at all, then the study may be
reinstated at the will of the commissionerreinstated at the will of the commissioner
25. Upon Disqualification…Upon Disqualification…
If the commissioner finds that the facility wasIf the commissioner finds that the facility was
noncompliant on any of the grounds after the hearing,noncompliant on any of the grounds after the hearing,
then a final order of noncompliance will be sent to thethen a final order of noncompliance will be sent to the
facility with explanationsfacility with explanations
If a testing facility has been disqualified, any studiesIf a testing facility has been disqualified, any studies
done before of after the disqualification will need to bedone before of after the disqualification will need to be
determined as essential to a decision (acceptable or not)determined as essential to a decision (acceptable or not)
If the study is determined unacceptable, then the facilityIf the study is determined unacceptable, then the facility
itself may need to show that the study was not affecteditself may need to show that the study was not affected
by the noncompliance that led to the disqualificationby the noncompliance that led to the disqualification
Once finally disqualified, the facility may not receive orOnce finally disqualified, the facility may not receive or
be considered for a research or marketing permit and thebe considered for a research or marketing permit and the
study is rejected.study is rejected.
26. Upon Disqualification…Upon Disqualification…
The commissioner may notify the public and allThe commissioner may notify the public and all
interested persons, including other federal agencies theinterested persons, including other federal agencies the
facility may have contactedfacility may have contacted
The FDA may ask the other agencies to considerThe FDA may ask the other agencies to consider
whether to support the facility or not under thewhether to support the facility or not under the
disqualificationdisqualification
Civil or criminal proceedings may occur at the discretionCivil or criminal proceedings may occur at the discretion
of the commissionerof the commissioner
Fines of up to $50,000 if one knowingly commits crime and/orFines of up to $50,000 if one knowingly commits crime and/or
1 year imprisonment~ for registration applicants and1 year imprisonment~ for registration applicants and
producersproducers
Fines up to $5,000 all others~ civil penalty after failing toFines up to $5,000 all others~ civil penalty after failing to
improve after a minor violation warning was issued~ onlyimprove after a minor violation warning was issued~ only
those involved in testing will be given civil penaltiesthose involved in testing will be given civil penalties
Those involved in the distribution or sales will be assessedThose involved in the distribution or sales will be assessed
more heavy penalties, such as criminal penaltiesmore heavy penalties, such as criminal penalties
27. Upon Disqualification…Upon Disqualification…
The FDA may turn it over to the federal,The FDA may turn it over to the federal,
state or local law enforcementstate or local law enforcement
The facility’s sponsor may terminate orThe facility’s sponsor may terminate or
suspend the facility from doing any non-suspend the facility from doing any non-
clinical study for a permitclinical study for a permit
The sponsor is required to notify the FDAThe sponsor is required to notify the FDA
in writing within 15 working days that thein writing within 15 working days that the
facility is to be suspended or terminatedfacility is to be suspended or terminated
and whyand why
28. Reinstatement of a DisqualifiedReinstatement of a Disqualified
FacilityFacility
The testing facility may be reinstated asThe testing facility may be reinstated as
acceptable non-clinical study to be turned intoacceptable non-clinical study to be turned into
the FDA if the commissioner can be certain thatthe FDA if the commissioner can be certain that
future studies will be conducted in compliancefuture studies will be conducted in compliance
with the Good Laboratory Practice standardswith the Good Laboratory Practice standards
and that any current studies integrity have notand that any current studies integrity have not
been severely harmed by the disqualificationbeen severely harmed by the disqualification
The disqualified facility will be required to put inThe disqualified facility will be required to put in
writing to the commissioner reasons why itwriting to the commissioner reasons why it
should be reinstated and any actions the facilityshould be reinstated and any actions the facility
will take or have taken to assure anywill take or have taken to assure any
disqualification problems will not happen againdisqualification problems will not happen again
29. Reinstatement of a DisqualifiedReinstatement of a Disqualified
FacilityFacility
The commissioner will inspect the facilityThe commissioner will inspect the facility
and determine if it shall be reinstatedand determine if it shall be reinstated
If it is reinstated, the commissioner isIf it is reinstated, the commissioner is
required to notify all persons that wererequired to notify all persons that were
notified of the disqualification including thenotified of the disqualification including the
facility itselffacility itself
