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GLP or GLP or Good Laboratory Good Laboratory Practices Practices
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GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Dec 26, 2015

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Page 1: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

GLP or GLP or Good Laboratory Good Laboratory

PracticesPractices

Page 2: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

GLP: GOOD LABORATORY GLP: GOOD LABORATORY PRACTICEPRACTICE

GLP GLP is an FDA regulation.is an FDA regulation. DefinitionDefinition: GLP embodies : GLP embodies

a set of principles that a set of principles that provides a framework provides a framework within which laboratory within which laboratory studies are planned studies are planned performed, monitored, performed, monitored, reported and archived.reported and 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.

Page 3: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 Although GLP originated in the United States , it had a

world wide impact.world 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 States had to comply with the United States GLP regulations.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.

Page 4: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 laboratory practice all over the United States.the 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 They discovered a lot fraudulent activities and a lot fraudulent activities and a lot of poor lab practices.of poor lab practices.

Examples of some of these Examples of some of these poor lab practices found were poor lab practices found were

1.1. Equipment not been Equipment not been calibrated to standard form , calibrated to standard form , therefore giving wrong therefore giving wrong measurements.measurements.

2.2. Incorrect/inaccurate accounts Incorrect/inaccurate accounts of the actual lab studyof the actual lab study

3.3. Inadequate test systemsInadequate test systems

Page 5: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 lab eventually served jail time.time.

Page 6: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

OBJECTIVES OF GLPOBJECTIVES OF GLP

GLP makes sure that the data GLP makes sure that the data submitted are a true reflection of the submitted are a true reflection of the results that are obtained during the results that are obtained during the study.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.

Page 7: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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

Page 8: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 They define how to carry out protocol-specified activities.protocol-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

Page 9: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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

Page 10: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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.

Page 11: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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-The frequency for calibration, re-validation and testing depends on the validation and testing depends on the instrument and extent of its use in the instrument and extent of its use in the laboratory.laboratory.

Whenever an instrument’s performance Whenever an instrument’s performance is outside the “control limits” reports is outside the “control limits” reports must be discontinued must be discontinued

Page 12: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Instrument Validation (cont)Instrument Validation (cont)

Equipment records should include:Equipment records should include: Name of the equipment and Name of the equipment and

manufacturermanufacturer 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)

Page 13: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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.

Page 14: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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

Page 15: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Analyst CertificationAnalyst Certification

Some acceptable proof of satisfactory Some acceptable proof of satisfactory training and/or competence with specific training and/or competence with specific laboratory procedures must be established laboratory procedures must be established for each analyst.for each analyst.

Qualification can come from education, Qualification can come from education, experience or additional trainings, but it experience or additional trainings, but it should be documentedshould be documented

Sufficient peopleSufficient people Requirements of certification varyRequirements of certification vary

Page 16: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Laboratory CertificationLaboratory Certification

Normally done by an external agencyNormally done by an external agency Evaluation is concerned with issues such Evaluation is concerned with issues such

as as Adequate spaceAdequate space VentilationVentilation StorageStorage HygieneHygiene

Page 17: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 connected with the set of analytical data.data.

Page 18: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Documentation and Documentation and Maintenance of RecordsMaintenance of 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 event of legal challenges due to repercussions of decisions based on the repercussions of decisions based on the original analytical results.original analytical 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 should be maintained will vary with the situationsituation

Page 19: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Good Documentation Good Documentation PracticePractice

Documentation should permit the Documentation should permit the

complete complete reconstructionreconstruction of a study of a study

Record data directly, promptly and legibly in Record data directly, promptly and legibly in

indelible ink (never pencil)indelible ink (never pencil)

Initial and date all observations and any resulting Initial and date all observations and any resulting changes, but do not obscure original datachanges, but do not obscure original data

Initial and date only work you’ve performedInitial and date only work you’ve performed

Do not document selectively or in advance of Do not document selectively or in advance of performing the activityperforming the activity

Page 20: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Good Documentation Good Documentation PracticePractice

Do not use white-out correction fluid or tapeDo not use white-out correction fluid or tape Do not use ditto marks as raw dataDo not use ditto marks as raw data Copy all heat sensitive paper and stamp Copy all heat sensitive paper and stamp

“exact copy”“exact copy” Explain why any raw data not used was not Explain why any raw data not used was not

usedused Verify critical calculations using a second Verify critical calculations using a second

person and document thisperson and document this Notebook pages requiring a second signature Notebook pages requiring a second signature

shall be completed with that signature shall be completed with that signature

Page 21: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Good Documentation Good Documentation PracticePractice

Properly head all pages, tables, columns; Properly head all pages, tables, columns; identify unitsidentify units

Describe Statistical & Calculation Describe Statistical & Calculation Procedures usedProcedures used

Sign, Date, and File automated printouts Sign, Date, and File automated printouts (e.g., QC forms)(e.g., QC forms)

Retain all Raw Data (original records) in the Retain all Raw Data (original records) in the Study FileStudy File

Do not document by exception. Use positive Do not document by exception. Use positive documentation, even if only a check mark. documentation, even if only a check mark.

Page 22: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Good Documentation Good Documentation PracticePractice

Documentation must allow another Documentation must allow another person to be able to accurately person to be able to accurately reconstruct what you have done reconstruct what you have done

Keep all Keep all originaloriginal observations observations including including those observations recorded directly those observations recorded directly into a computerinto a computer

Sign and date all computer printoutsSign and date all computer printouts Never back-date anythingNever back-date anything

Follow SOPs and ProtocolFollow SOPs and Protocol

Page 23: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Good Documentation Good Documentation PracticePractice

Document all deviations with Document all deviations with accompanying explanationsaccompanying explanations

Indicate in the record all applicable units Indicate in the record all applicable units and equipment usedand equipment used

Page 24: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Important questions to be answered Important questions to be answered for any analytical instrumentfor any 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, If the instrument is not within specifications, how much does it deviate by?how much does it deviate by?

If the instrument is not within specifications If the instrument is not within specifications what action has been taken to overcome the what action has been taken to overcome the defect?defect?

Can the standards used to test and calibrate Can the standards used to test and calibrate the instrument be traced back to national the instrument be traced back to national standards?standards?

Page 25: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

What happens if a What happens if a workplace does not comply workplace does not comply

with federal Good with federal Good Laboratory Practice Laboratory Practice

standards?standards?

Page 26: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Disqualification of a Facility Disqualification of a Facility Before a workplace can experience Before a workplace can experience

the consequences of noncompliance, the consequences of noncompliance, an explanation of disqualification is an 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 laboratory studies or starting any new studies due to not following the new 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

Page 27: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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

Page 28: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Grounds for DisqualificationGrounds for Disqualification

The testing facility failed to comply The testing facility failed to comply with one or more regulations with one or more regulations implemented by the GLP manualimplemented by the GLP manual

The failure to comply led to adverse The failure to comply led to adverse outcomes in the data; in other words, outcomes in the data; in other words, it affected the validity of the studyit affected 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

Page 29: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Consequences of Consequences of NoncomplianceNoncompliance

The FDA states the following consequences of The FDA states the following consequences of noncompliance:noncompliance: The commissioner will send a written proposal The commissioner will send a written proposal

of disqualification to the testing facilityof disqualification to the testing facility A regulatory hearing on the disqualification will A regulatory hearing on the disqualification will

be scheduledbe scheduled If the commissioner finds that after the hearing, If the commissioner finds that after the hearing,

the facility has complied, then a written the facility has complied, then a written statement with an explanation of termination of statement 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 Thus, if it can be shown that such disqualifications did not affect the integrity and disqualifications did not affect the integrity and outcome of the study itself, or did not occur at outcome of the study itself, or did not occur at all, then the study may be reinstated at the will all, then the study may be reinstated at the will of the commissionerof the commissioner

Page 30: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 hearing, then a final order of noncompliance will be sent to the facility with explanations will be sent to the facility with explanations

If a testing facility has been disqualified, any If a testing facility has been disqualified, any studies done before of after the disqualification studies done before of after the disqualification will need to be determined as essential to a will need to be determined as essential to a decision (acceptable or not)decision (acceptable 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 facility itself may need to show that the study was not affected by the noncompliance that led was not affected by the noncompliance that led to the disqualificationto the disqualification

Once finally disqualified, the facility may not Once finally disqualified, the facility may not receive or be considered for a research or receive or be considered for a research or marketing permit and the study is rejected.marketing permit and the study is rejected.

Page 31: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 interested persons, including other federal agencies the facility may have contactedagencies the 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 Fines of up to $50,000 if one knowingly commits

crime and/or 1 year imprisonment~ for registration crime and/or 1 year imprisonment~ for registration applicants and producersapplicants and producers

Fines up to $5,000 all others~ civil penalty after Fines up to $5,000 all others~ civil penalty after failing to improve after a minor violation warning was failing to improve after a minor violation warning was issued~ only those involved in testing will be given issued~ only those involved in testing will be given civil penaltiescivil penalties

Those involved in the distribution or sales will be Those involved in the distribution or sales will be assessed more heavy penalties, such as criminal assessed more heavy penalties, such as criminal penaltiespenalties

Page 32: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

Upon Disqualification…Upon Disqualification…

The FDA may turn it over to the The FDA may turn it over to the federal, state or local law enforcementfederal, state or local law enforcement

The facility’s sponsor may terminate The facility’s sponsor may terminate or suspend the facility from doing any or suspend the facility from doing any non- clinical study for a permitnon- clinical study for a permit

The sponsor is required to notify the The sponsor is required to notify the FDA in writing within 15 working days FDA in writing within 15 working days that the facility is to be suspended or that the facility is to be suspended or terminated and whyterminated and why

Page 33: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 the FDA if the commissioner can be certain that future studies will be conducted in that future studies will be conducted in compliance with the Good Laboratory Practice compliance with the Good Laboratory Practice standards and that any current studies standards and that any current studies integrity have not been severely harmed by integrity have not been severely harmed by the disqualificationthe disqualification

The disqualified facility will be required to put The disqualified facility will be required to put in writing to the commissioner reasons why it in writing to the commissioner reasons why it should be reinstated and any actions the should be reinstated and any actions the facility will take or have taken to assure any facility will take or have taken to assure any disqualification problems will not happen disqualification problems will not happen againagain

Page 34: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

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 required to notify all persons that were notified of the disqualification were notified of the disqualification including the facility itself including the facility itself

Page 35: GLP or Good Laboratory Practices. GLP: GOOD LABORATORY PRACTICE GLP is an FDA regulation. GLP is an FDA regulation. Definition: GLP embodies a set of.

ReferencesReferences

http://www.sjsu.edu/faculty/chem55/55glpout.htm

http://www.labcompliance.com/tutorial/glp/default.aspx?sm=d_a

WikipediaWikipedia