Good laboratory practices (GLP) himanshu

Good Laboratory Practices (GLP)
History
Reason behind GLP created
Advantages and disadvantages of GLP
Objectives of GLP
Practice of GLP
b pharma 6th sem
pharmaceutical quality assurance

1. Good Laboratory Practices
(GLP)
Himanshu Kamboj
Assistant Professor

2. Contents
Good Laboratory Practices (GLP)
History
Reason behind GLP created
Advantages and disadvantages of GLP
Objectives of GLP
Practice of GLP

3. GLP: GOOD LABORATORY
PRACTICE
GLPisanFDAregulation.
Definition:GLPembodiesasetofprinciplesthat
providesaframeworkwithinwhichlaboratorystudiesare
plannedperformed,monitored,reportedandarchived.
GLPissometimesconfusedwiththestandardsof
laboratorysafetylikewearingsafetygoggles.
GLPhelpassureregulatoryauthoritiesthatthedatasubmittedarea
truereflectionoftheresultsobtainedduringthestudyandcan
thereforebeconfidenceuponwhenmarkingrisk/safetyassessment.

4. HISTORY
GLPisaformalregulationthatwascreatedbytheFDA(Unitedstatesfood
anddrugadministration)in1978.
AlthoughGLPoriginatedintheUnitedStates,ithadaworldwideimpact.
Non-UScompaniesthatwantedtodobusinesswiththeUnitedstatesor
registertheirpharmaciesintheUnitedStateshadtocomplywiththeUnited
StatesGLPregulations.
TheyeventuallystartedmakingGLPregulationsintheirhomecountries.
In1981anorganizationnamedOECD(organizationforeconomicco-
operationanddevelopment)producedGLPprinciplesthatareinternational
standard.
GLPinOECDprinciplesisdefinedas“aqualitysystemconcernedwiththe
organizationalprocessandtheconditionsunderwhichnon-clinicalhealth
andenvironmentalsafetystudiesareplanned,performed,monitored,
recorded,archivedandreported”.

5. REASON BEHIND GLP CREATED
Intheearly70’sFDAbecameawareofcasesofpoorlaboratory
practiceallovertheUnitedStates.
FDAdecidedtodoanin-depthinvestigationon40toxicology
labs.
Theydiscoveredalotfraudulentactivitiesandalotofpoorlab
practices.
Examplesofsomeofthesepoorlabpracticesfoundwere
1.Equipmentnotbeencalibratedtostandardform,therefore
givingwrongmeasurements.
2.Incorrect/inaccurateaccountsoftheactuallabstudy
3.Inadequatetestsystems

6. FAMOUS EXAMPLE
Oneofthelabsthatwentundersuchaninvestigationmade
headlinenews.
ThenameoftheLabwasIndustrialBioTest.Thiswasabiglab
thatrantestsforbigcompaniessuchasProcterandGamble.
Itwasdiscoveredthatmicethattheyhadusedtotestcosmetics
suchaslotionanddeodorantshaddevelopedcanceranddied.
IndustrialBioTestlabthrewthedeadmiceandcoveredresults
deemingtheproductsgoodforhumanconsumption.
Thoseinvolvedinproduction,distributionandsalesforthelab
eventuallyservedjailtime.

7. ADVANTAGESOFGLP
Assuresthatthedataareatruereflectionofresultsobtained
fromstudies.
Preclinicalsafetyandresiduesafety.
Generationofhighqualityandreliabletestdata.
Mutualacceptanceofdata
Increasespublicconfidence.
Shortensthetime-to-marketfornewproducts.
DISADVANTAGESOFGLP
Moremanpowerisrequired.
Expensiveprocess.
Timeconsumingprocess.

8. OBJECTIVES OF GLP
GLPmakessurethatthedatasubmittedareatruereflectionofthe
resultsthatareobtainedduringthestudy.
GLPalsomakessurethatdataistraceable.
Promotesinternationalacceptanceoftests.

9. PRACTICE OF GLP
Generalprovisions
OrganizationandPersonnel
Facilities
Equipment
Testingfacilitiesoperation
Testandcontrolarticles
Protocolforandtheconductofthestudy
RecordsandReports

10. Generalprovisions
1)ItprescribesGLPforconductingnon-clinicallaboratorystudies
thatsupportresearchandmarketingpermitsofproductsregulated
byFDA.
2)Applicabilitytostudiesperformedundergrantsandcontracts.
3)Inspectionofthetestingfacility.

11. OrganizationandPersonnel
1)Organization
2)Personnel
3)Testingfacilitymanagement
4)Studydirector
5)Qualityassuranceunit

12. Organization-Functions
1)Identificationofqualityactivities.
2)Dividingthejobsamongthepersonnel.
3)Definetheauthorityandresponsibilityofeachjoband
relationshipofeachjobwithotherjobs.
4)Coordinatetheworkofinternaldepartmentsandoutside
agencies

13. Personnel
Eachindividualengagedintheconductorsupervisionofnonclinical
laboratorystudyshallhave:
1)Education
2)Training
a)Generaltraining
b)Specifictraining
3)Experienceorcombination
4)Personalsanitationandhealthprecautions

14. Testingfacilitymanagement
1)Asufficientnumberofqualifiedpersonnel,appropriatefacilities,
equipmentandmaterialsareavailableforconductanceofthestudy.
2)Maintenanceofrecordsofqualifications,trainingandexperience
ofpersonnelandtheirjobdescription.
3)Appointmentofstudydirector.
4)Qualityassuranceprogramwithdesignatedpersonnel

15. StudyDirector
Ascientistorotherprofessionalofappropriateeducation,trainingand
experience.Responsibilitiesofthestudydirectorare:
1)Approvalofprotocolandstudyplansincludingamendments.
2)Technicalconductofthestudy.
3)EnsurethattheQApersonnelandstudypersonnelareupdated
withthestudyplanandSOPs.
4)Interpretation,analysis,documentationandreportingoftheresults.
5)Alsochecksthatexperimentaldataisaccuratelyrecordedand
verified.
6)Signanddatethefinalreportforacceptanceofdata.

16. QualityAssuranceUnit
1)Anindividualoragroupdesignatedbymanagementtoassure
thatthestudiesareincompliancewithGLPprinciples.
2)Monitorsthestudytoassuremanagementthatthefacilities,
equipment,personnel,methods,practices,recordsandcontrolsare
inconformancewiththeregulations.
3)Maintainthecopiesofmasterschedulesheet,protocolandSOPs.
4)AccesstoupdatedstudyplansandSOPs.
5)DocumentedverificationofcomplianceofthestudywithGLP
principles.

17. QualityAssuranceUnit
6)InspectionstodeterminethecomplianceofthestudywithGLP
principlesandthreetypeofinspectionsare:
a)Studybasedinspections
b)Processbasedinspections
c)Facilitybasedinspections
7)Determinesanydeviationfromtheapprovedprotocolandreport
toSD,PIandmanagement.
8)Preparestatementstobeincludedinthefinalreportcontaining
datesandtypesofinspection.

18. C.Facilities
1)Generalfacilities:
a)Testingsystemfacilities
b)Archivefacilities
c)Wastedisposal
2)Animalcarefacilities

19. Generalfacilities
Testingsystemfacilities
Suitablesize,constructionandlocation.
Adequatedegreeofseparationofdifferentactivities.
Laboratoriesshouldbewellventilated,freeofdust,draftsand
extremetemperatures.
Minimum150sq.feetoffloorspaceandminimum6linearfeetof
usablebenchspaceshouldbeprovideforeachanalyst.
Archivefacilities-Securestorageandretrievalofstudyplans,raw
data,finalreportandspecimenstopreventuntimelydeterioration.
Wastedisposal-Appropriatecollection,storageanddisposal
facilitiesanddecontaminationprocedures.

20. Animalcarefacilities
1)Locatedawayformtestinglaboratoriespreferablyinaseparate
building.
2)Contaminationriskisreducedby“barrier”system,aswellasby
providing“clean”and“dirty”corridors.
3)Separateareasforanimalsofdifferentspeciesandstudies.
4)Separateareasfordiagnosis,treatmentandcontrolof
laboratoryanimaldiseases.
5)Lighteningshouldbeproperaslightintensityandnoiselevelis
sufficient.
6)Maintainroomtemperature,humidityandairchangesinanimal
quarters.

21. D.Equipment
1)Appropriatedesignandadequatecapacity.
2)Equipmentshallbeadequatelyinspected,cleanedand
maintained.
3)Equipmentusedforgeneration,measurementorassessmentof
datashallbeadequatelytested,calibratedandstandardized.
4)Logbooksforeachequipmentshouldbethere

22. MISSION OF GLP
Test systems
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

23. Standard Operating Procedures (SOP)
Writtenproceduresforalaboratoriesprogram.
Theydefinehowtocarryoutprotocol-specifiedactivities.
Mostoftenwritteninachronologicallistingofactionsteps.
Theyarewrittentoexplainhowtheproceduresaresupposetowork

24. SOP
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. 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.

26. Instrumentation Validation
This is a process necessary for any analytical laboratory.
Data produced by “faulty” instruments may give the appearance of
valid data.
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

27. Instrument Validation (cont)
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)

28. Reagent/ Materials Certification
Thispolicyistoassurethatreagentsusedarespecifiedinthe
standardoperatingprocedure.
Purchasingandtestingshouldbehandledbyaqualityassurance
program.

29. Reagents and Solutions
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

30. Analyst Certification
Someacceptableproofofsatisfactorytrainingand/orcompetence
withspecificlaboratoryproceduresmustbeestablishedforeach
analyst.
Qualificationcancomefromeducation,experienceoradditional
trainings,butitshouldbedocumented
Sufficientpeople
Requirementsofcertificationvary

31. Laboratory Certification
Normally done by an external agency evaluation is
concerned with issues such as
Adequate space
Ventilation
Storage
Hygiene

32. Specimen/Sample Tracking
Vary among laboratories
Must maintain the unmistakable 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.

33. Documentation and Maintenance
of Records
Maintenanceofallrecordsprovidedocumentationwhich
mayberequiredintheeventoflegalchallengesdueto
repercussionsofdecisionsbasedontheoriginalanalytical
results.
Generalguidelinesfollowedinregulatedlaboratoriesisto
maintainrecordsforatleastfiveyears
Lengthoftimeoverwhichlaboratoryrecordsshouldbe
maintainedwillvarywiththesituation

34. Good Documentation
Practice
Documentation should permit the complete
reconstructionof a study
Record data directly, promptly and legibly in indelible
ink (never pencil)
Initial and date all observations and any resulting
changes, but do not obscure original data
Initial and date only work you’ve performed
Do not document selectively or in advance of
performing the activity

35. Good Documentation Practice
Do not use white-out correction fluid or tape
Do not use ditto marks as raw data
Copy all heat sensitive paper and stamp “exact
copy”
Explain why any raw data was not used
Verify critical calculations using a second person
and document this
Notebook pages requiring a second signature
shallbe completed with that signature

36. Good Documentation Practice
Properly head all pages, tables, columns; identify
units
Describe Statistical & Calculation Procedures used
Sign, Date, and File automated printouts (e.g., QC
forms)
Retain all Raw Data (original records) in the Study
File
Do not document by exception. Use positive
documentation, even if only a check mark.

37. Good Documentation
Practice
Documentationmustallowanotherpersonto
beabletoaccuratelyreconstructwhatyou
havedone
Keepalloriginalobservationsincludingthose
observationsrecordeddirectlyintoa
computer
Signanddateallcomputerprintouts
Neverback-dateanything
FollowSOPsandProtocol

38. Good Documentation
Practice
Documentalldeviationswithaccompanying
explanations
Indicateintherecordallapplicableunitsand
equipmentused

39. Important questions to be answered for any
analytical instrument
Whatistheequipmentbeingusedfor?
Istheinstrumentwithinspecificationandisthe
documentationtoprovethisavailable?
Iftheinstrumentisnotwithinspecifications,how
muchdoesitdeviateby?
Iftheinstrumentisnotwithinspecificationswhat
actionhasbeentakentoovercomethedefect?
Canthestandardsusedtotestandcalibratethe
instrumentbetracedbacktonationalstandards?

40. What happens if a workplace
does not comply with federal
Good Laboratory Practice
standards?

41. Disqualification of a Facility
Beforeaworkplacecanexperiencetheconsequencesof
noncompliance,anexplanationofdisqualificationisneeded
TheFDAstatesthepurposeofdisqualificationastheexclusionofa
testingfacilityfromcompletinglaboratorystudiesorstartingany
newstudiesduetonotfollowingthestandardsofcompliancesetby
theGoodLaboratoryPracticemanual

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

43. Grounds for Disqualification
Thetestingfacilityfailedtocomplywithoneormoreregulations
implementedbytheGLPmanual
Thefailuretocomplyledtoadverseoutcomesinthedata;inother
words,itaffectedthevalidityofthestudy
Warningsorrejectionofpreviousstudieshavenotbeenadequate
toimprovethefacility’scompliance

44. 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

45. Upon Disqualification…
Ifthecommissionerfindsthatthefacilitywas
noncompliantonanyofthegroundsafterthehearing,
thenafinalorderofnoncompliancewillbesenttothe
facilitywithexplanations
Ifatestingfacilityhasbeendisqualified,anystudies
donebeforeofafterthedisqualificationwillneedtobe
determinedasessentialtoadecision(acceptableornot)
Ifthestudyisdeterminedunacceptable,thenthefacility
itselfmayneedtoshowthatthestudywasnotaffected
bythenoncompliancethatledtothedisqualification
Oncefinallydisqualified,thefacilitymaynotreceiveor
beconsideredforaresearchormarketingpermitand
thestudyisrejected.

46. Upon Disqualification…
Thecommissionermaynotifythepublicandall
interestedpersons,includingotherfederalagenciesthe
facilitymayhavecontacted
TheFDAmayasktheotheragenciestoconsiderwhether
tosupportthefacilityornotunderthedisqualification
Civilorcriminalproceedingsmayoccuratthediscretion
ofthecommissioner
Finesofupto$50,000ifoneknowinglycommitscrimeand/or
1yearimprisonment~forregistrationapplicantsand
producers
Finesupto$5,000allothers~civilpenaltyafterfailingto
improveafteraminorviolationwarningwasissued~only
thoseinvolvedintestingwillbegivencivilpenalties
Thoseinvolvedinthedistributionorsaleswillbeassessed
moreheavypenalties,suchascriminalpenalties

47. Upon Disqualification…
TheFDAmayturnitovertothefederal,stateorlocallaw
enforcement
Thefacility’ssponsormayterminateorsuspendthefacilityfrom
doinganynon-clinicalstudyforapermit
ThesponsorisrequiredtonotifytheFDAinwritingwithin15
workingdaysthatthefacilityistobesuspendedorterminated
andwhy

48. Reinstatement of a Disqualified
Facility
Thetestingfacilitymaybereinstatedas
acceptablenon-clinicalstudytobeturnedinto
theFDAifthecommissionercanbecertainthat
futurestudieswillbeconductedincompliance
withtheGoodLaboratoryPracticestandardsand
thatanycurrentstudiesintegrityhavenotbeen
severelyharmedbythedisqualification
Thedisqualifiedfacilitywillberequiredtoputin
writingtothecommissionerreasonswhyit
shouldbereinstatedandanyactionsthefacility
willtakeorhavetakentoassureany
disqualificationproblemswillnothappenagain

49. Reinstatement of a Disqualified
Facility
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

50. THANK YOU