GOOD LABORATORY PRACTICE, GOOD LABORATORY PRACTICE

PPT GLP

1. Good Laboratory PracticesGood Laboratory Practices

2. GLP: GOOD LABORATORY GLP: GOOD LABORATORY
PRACTICEPRACTICE

GLP GLP is an FDA regulation.is an FDA regulation.

DefinitionDefinition: GLP embodies a : GLP embodies a
set of principles that set of principles that
provides a framework within provides a framework within
which laboratory studies are which laboratory studies are
planned performed, planned performed,
monitored, reported and monitored, reported and
archived.archived.

GLP is sometimes confused GLP is sometimes confused
with the standards of with the standards of
laboratory safety like laboratory safety like
wearing safety goggles.wearing safety goggles.

3. HISTORYHISTORY

GLP is a formal regulation that was created by the FDA GLP is a formal regulation that was created by the FDA
(United states food and drug administration) in 1978.(United states food and drug administration) in 1978.

Although GLP originated in the United States , it had a world Although GLP originated in the United States , it had a world
wide impact.wide impact.

Non-US companies that wanted to do business with the Non-US companies that wanted to do business with the
United states or register their pharmacies in the United United states or register their pharmacies in the United
States had to comply with the United States GLP regulations.States had to comply with the United States GLP regulations.

They eventually started making GLP regulations in their They eventually started making GLP regulations in their
home countries.home countries.

In 1981 an organization named OECD (organization for In 1981 an organization named OECD (organization for
economic co-operation and development ) produced GLP economic co-operation and development ) produced GLP
principles that are international standard.principles that are international standard.

4. WHY WAS GLP CREATED?WHY WAS GLP CREATED?

In the early 70’s FDA became In the early 70’s FDA became
aware of cases of poor aware of cases of poor
laboratory practice all over the laboratory practice all over the
United States.United States.

FDA decided to do an in-depth FDA decided to do an in-depth
investigation on 40 toxicology investigation on 40 toxicology
labs.labs.

They discovered a lot fraudulent They discovered a lot fraudulent
activities and a lot of poor lab activities and a lot of poor lab
practices.practices.

Examples of some of these poor Examples of some of these poor
lab practices found were lab practices found were
1.1.Equipment not been calibrated Equipment not been calibrated
to standard form , therefore to standard form , therefore
giving wrong measurements.giving wrong measurements.
2.2.Incorrect/inaccurate accounts of Incorrect/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 went One of the labs that went
under such an investigation under such an investigation
made headline news.made headline news.

The name of the Lab was The name of the Lab was
Industrial Bio Test. This was a Industrial Bio Test. This was a
big lab that ran tests for big big lab that ran tests for big
companies such as Procter companies such as Procter
and Gamble.and Gamble.

It was discovered that mice It was discovered that mice
that they had used to test that they had used to test
cosmetics such as lotion and cosmetics such as lotion and
deodorants had developed deodorants had developed
cancer and died.cancer and died.

Industrial Bio Test lab threw Industrial Bio Test lab threw
the dead mice and covered the dead mice and covered
results deeming the products results deeming the products
good for human consumption.good for human consumption.

Those involved in production, Those involved in production,
distribution and sales for the distribution 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 submitted GLP makes sure that the data submitted
are a true reflection of the results that are a true reflection of the results that
are obtained during the study.are obtained during the study.

GLP also makes sure that data is GLP also makes sure that data is
traceable.traceable.

Promotes international acceptance of Promotes 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 Procedures Standard Operating Procedures
(SOP)(SOP)

Written procedures for a laboratories Written 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 Most often written in a chronological
listing of action steps.listing of action steps.

They are written to explain how the They 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 to Actions 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 Data Statistical Procedures for Data
EvaluationEvaluation

Statistical procedures are not simply Statistical procedures are not simply
chosen from a text bookchosen from a text book

Practitioners in a particular field may Practitioners in a particular field may
adopt certain standards which are adopt certain standards which are
deemed acceptable within that field.deemed acceptable within that field.

Regulatory agencies often describe Regulatory agencies often describe
acceptable statistical procedures.acceptable statistical procedures.

11. Instrumentation ValidationInstrumentation Validation

This is a process necessary for any This is a process necessary for any
analytical laboratory.analytical laboratory.

Data produced by “faulty” instruments Data produced by “faulty” instruments
may give the appearance of valid data.may give the appearance of valid data.

The frequency for calibration, re-validation The frequency for calibration, re-validation
and testing depends on the instrument and 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 is Whenever an instrument’s performance is
outside the “control limits” reports must outside the “control limits” reports must
be discontinued be discontinued

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 the Date equipment was received in the
laboratorylaboratory

Copy of manufacturers operating Copy of manufacturers operating
instruction (s)instruction (s)

13. Reagent/ Materials Reagent/ Materials
CertificationCertification

This policy is to assure that reagents This policy is to assure that reagents
used are specified in the standard used are specified in the standard
operating procedure.operating procedure.

Purchasing and testing should be Purchasing and testing should be
handled by a quality assurance handled by a quality assurance
program.program.

14. Reagents and Solutions contReagents and Solutions cont

Requirements:Requirements:

Reagents and solutions shall be labeled Reagents and solutions shall be labeled

Deteriorated or outdated reagents and Deteriorated 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 satisfactory training Some acceptable proof of satisfactory training
and/or competence with specific laboratory and/or competence with specific laboratory
procedures must be established for each procedures must be established for each
analyst.analyst.

Qualification can come from education, Qualification can come from education,
experience or additional trainings, but it should experience or additional trainings, but it should
be documentedbe 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 as Evaluation 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 unmistakable Must maintain the unmistakable
connection between a set of analytical connection between a set of analytical
data and the specimen and/or samples data 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 unmistakably must be recorded and unmistakably
connected with the set of analytical data.connected with the set of analytical data.

18. Documentation and Maintenance Documentation and Maintenance
of Recordsof Records

Maintenance of all records provide Maintenance of all records provide
documentation which may be required in the documentation which may be required in the
event of legal challenges due to repercussions event of legal challenges due to repercussions
of decisions based on the original analytical of decisions based on the original analytical
results.results.

General guidelines followed in regulated General guidelines followed in regulated
laboratories is to maintain records for at least laboratories is to maintain records for at least
five yearsfive years

Length of time over which laboratory records Length 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 Important questions to be answered for
any analytical instrumentany analytical instrument

What is the equipment being used for?What is the equipment being used for?

Is the instrument within specification and is the Is the instrument within specification and is the
documentation to prove this available?documentation to prove this available?

If the instrument is not within specifications, how If the instrument is not within specifications, how
much does it deviate by?much does it deviate by?

If the instrument is not within specifications what If 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 the Can 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 workplace What happens if a workplace
does not comply with federal does not comply with federal
Good Laboratory Practice Good Laboratory Practice
standards?standards?

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

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 Falsifying information related to
testing~ protocols, ingredients, testing~ protocols, ingredients,
observations, data equipment, ect.observations, data equipment, ect.

Failure to prepare, retain, or submit Failure to prepare, retain, or submit
written records required by lawwritten records required by law

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

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

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

26. Upon Disqualification…Upon Disqualification…

The commissioner may notify the public and all The commissioner may notify the public and all
interested persons, including other federal agencies interested persons, including other federal agencies
the facility may have contactedthe facility may have contacted

The FDA may ask the other agencies to consider The FDA may ask the other agencies to consider
whether to support the facility or not under the whether to support the facility or not under the
disqualificationdisqualification

Civil or criminal proceedings may occur at the Civil or criminal proceedings may occur at the
discretion of the commissionerdiscretion of the commissioner

Fines of up to $50,000 if one knowingly commits crime Fines of up to $50,000 if one knowingly commits crime
and/or 1 year imprisonment~ for registration applicants and/or 1 year imprisonment~ for registration applicants
and producersand producers

Fines up to $5,000 all others~ civil penalty after failing to Fines up to $5,000 all others~ civil penalty after failing to
improve after a minor violation warning was issued~ only improve 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 assessed Those 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 or The 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 FDA The sponsor is required to notify the FDA
in writing within 15 working days that the in writing within 15 working days that the
facility is to be suspended or terminated facility is to be suspended or terminated
and whyand why

28. Reinstatement of a Disqualified Reinstatement of a Disqualified
FacilityFacility

The testing facility may be reinstated as The testing facility may be reinstated as
acceptable non-clinical study to be turned into acceptable non-clinical study to be turned into
the FDA if the commissioner can be certain that the FDA if the commissioner can be certain that
future studies will be conducted in compliance future studies will be conducted in compliance
with the Good Laboratory Practice standards with the Good Laboratory Practice standards
and that any current studies integrity have not and 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 in The disqualified facility will be required to put in
writing to the commissioner reasons why it writing to the commissioner reasons why it
should be reinstated and any actions the facility should be reinstated and any actions the facility
will take or have taken to assure any will take or have taken to assure any
disqualification problems will not happen againdisqualification problems will not happen again

29. Reinstatement of a Disqualified Reinstatement of a Disqualified
FacilityFacility

The commissioner will inspect the The commissioner will inspect the
facility and determine if it shall be facility and determine if it shall be
reinstatedreinstated

If it is reinstated, the commissioner is If it is reinstated, the commissioner is
required to notify all persons that were required to notify all persons that were
notified of the disqualification including notified of the disqualification including
the facility itself the facility itself

30. ReferencesReferences

http://www.sjsu.edu/faculty/http://www.sjsu.edu/faculty/
chem55/55glpout.htmchem55/55glpout.htm

http://www.labcompliance.com/http://www.labcompliance.com/
tutorial/glp/default.aspx?sm=d_atutorial/glp/default.aspx?sm=d_a

UGA Office of the Vice President for UGA Office of the Vice President for
ResearchResearch

WikipediaWikipedia