glp and gcp

8/11/2019 GLP AND GCP

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Good Laboratory Practices&

Good Clinical Practices

Presented by:-

Mr. Swapnil L. PatilM.Pharm (Semester-2)Department of Pharmaceutics

Pad. Dr. D. Y. Patil College of Pharmacy,

Akurdi, Pune, Maharashtra, India, 411018.

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Good Laboratory Practices

.

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Contents:

Introduction

HistoryObjective

Rules and regulation

Noncompliance

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GLP: GOOD LABORATORY

PRACTICE GLP is an FDA regulation.

Definition: GLP embodies a

set of principles thatprovides a framework withinwhich laboratory studies are

planned , performed,monitored, recorded,reported and archived.

GLP is sometimes confusedwith the standards oflaboratory safety likewearing safety goggles.


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GOOD LABORATORY

PRACTICE

GLP applies to nonclinical studies

conducted for the assessment of the safety

or efficacyof chemicals (including

pharmaceuticals).

GLP helps assure regulatory authorities that

the data submitted are a true.5


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HISTORY

The formal regulatory conceptof Good

Laboratory Practice (GLP) originated in the

USA in the 1970s.

The FDAs publication of Proposed Regulations on

GLP in 1976, with establishment of the Final Rule in

June 1979 (21 CFR 58).

In 1981an organization named OECD produced

GLP principles that are international standard.6


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WHY WAS GLP CREATED?In the early 70s FDA became aware

of cases of ( PLP )poor laboratorypractice all over the United States.

FDA decided to do an in-depthinvestigation in 40 toxicology labs.

They discovered a lot fraudulent

activities and a lot of poor labpractices.

Examplesof some of these ( PLP )poor lab practices found were

Equipment not been calibrated to

standard form , therefore givingwrong measurements.

Incorrect/inaccurate accounts of theactual lab study

Inadequate plan


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FAMOUS EXAMPLE

One of the labs that went undersuch an investigation madeheadline news.

The name of the Lab wasIndustrial Bio Test. This was abig lab that ran tests for bigcompanies such as Procter andGamble.

It was discovered that mice thatthey had used to test lotion anddeodorants had developed cancerand died

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Industrial Bio Test lab threw the dead mice and coveredresults deeming the products good for human use.

Those involved in production, distribution and sales for

the IBT lab eventually served jail time.


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OBJECTIVES OF GLP

GLP makes sure that the data submitted are a

true reflectionof the results that are obtained

during the study. GLP also makes sure that data is traceable.

Promotes international acceptance of tests.


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MISSION OF GLP

Test systems

Archiving of records .Apparatus, material and reagent facilities.

Quality assurance programs.

Performance of the study.Reporting of study results.

Standard operating procedures (SOP)


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21 CFR Part 58: Non-Clinical

Laboratory Studies

Subpart A: General Provisions

Subpart B: Organization and Personnel

Subpart C: Facilities

Subpart D: Equipment

Subpart E: Testing Facilities Operation

Subpart F: Test and Control ArticlesSubpart G: Protocol for and Conduct of a Non-Clinical

Laboratory Study

Subpart J: Records and Reports

Subpart K: Disqualification of Testing Facilities 12


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GLP Regulations: Rules and Tools

Chemical and sample inventory,

expiration dates

TEST, CONTROL, AND

REFERENCE SUBSTANCES

Timely reporting, storage of raw

data and reports

RECORDS AND REPORTS

Standard operating proceduresFACILITY OPERATION

Calibration, logbooks of use, repair,

and maintenance

EQUIPMENT

Maintain adequate space/separationof chemicals from office areasFACILITIES

Training records, CVs, GLP trainingORGANIZATION AND

PERSONNEL

Documentation (Tools)GLP Regulations (Rules)

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Organization and Personnel

58.29 Personnel

(a)Each individual engaged in the conduct of or responsible

for the supervision of a nonclinical laboratory study shallhave education, training, and experience, or combination

thereof, to enable that individual to perform the assigned

functions.

(b)Each testing facility shall maintain a current summary of

training and experience and job description for each

individual engaged in or supervising the conduct of a

nonclinical laboratory study.14


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Organization and Personnel

58.33 Study Director

For each nonclinical laboratory

study, a scientist or other

professional of appropriate

education, training, andexperience, or combination

thereof, shall be identified as the

study director. The study director

has overall responsibility for the

technical conduct of the study,aswell as for the interpretation,

analysis, documentation, and

reporting of results, and represents

the single point of study control.

58.35 Quality Assurance

Unit

A testing facility shall have a

quality assurance unit which shall

be responsible for monitoring

each study to assure management

that the facilities, equipment,

personnel, methods, practices,

records, and controls are in

conformance with the regulations

in this part. For any given study,the quality assurance unit shall be

entirely separate from and

independent of the personnel

engaged in the direction and

conduct of that study. 15


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Facilities58.41 General

Each testing facility shall be of suitable size andconstructionto facilitate the proper conduct ofnonclinical laboratory studies. It shall be designed sothat there is a degree of separation that will prevent anyfunction or activity from having an adverse effect on thestudy.

Animal care facilities

Animal supply facilities

Facilities for handling test and control articles

Laboratory operation areas

Specimen and data storage facilities 16


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Equipment

58.61 Equipment Design

Equipment used in ... shall be of appropriate design and adequate capacity...

58.63 Maintenance and Calibration

(a) The written standard operating procedures ...

(b) Written records shall be maintained ...

Log book

Fit for use

Not for

GLPuse.

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Equipment Verification (Testing):

external check of

equipment accuracy (e.g.

check balance accuracy

against weights atlaboratory- no adjustment)

Calibration:equipment is

adjusted based on

comparison to certified or

known reference materials(e.g. balance adjusted after

comparison to certified

weights by trained

professional)

Standardization:

comparison with similar

equipment (e.g. use two

thermometers of similar

design to compare

readings)

Verification??

Calibration ? Standardization?

??

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Protocol , Reports and Records

58.120 Protocol

Each study shall have an approved written protocol that clearly indicates theobjectives and all methods for the conduct of the study.

58.130 Conduct of a Non-clinical Laboratory Study

The nonclinical laboratory study shall be conducted in accordance with theprotocol

58.185 Reporting of Non-clinical Laboratory Study Results

A final report shall be prepared for each nonclinical laboratory study ...

58.190 Storage and Retrieval of Records and Data

All raw data, documentation, protocols, final reports, and specimens ... shallbe retained.

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Raw Data

Definitions. Raw datameansany laboratory worksheets, records,

memoranda, notes, or exact copiesthereof, that are the result of originalobservations and activities of a study andare necessary for the reconstruction andevaluation of the report of that study.

If anyone scribble some notes on a scrap of paper,are those notes considered raw data?

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Raw Dataexamples of raw

data:-

Logbooks(to recordtemperatures or

equipment use, repair,

and maintenance) Field or laboratory

notebooks

Forms(for field orlaboratory

observations, chain-of-custody, sample or

chemical receipt)

Training reports

Computer printouts

Recorded data fromautomated instruments

Question:

What happens if youmake a mistake?

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40 CFR Part 160 (EPA GLP regulations)

Section 160.81 Standard operating procedures. (a) A testing

facility shall have standard operating procedures in writing

setting forth study methods that management is satisfied areadequate to insure the quality and integrity of the data

generated in the course of a study.

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

Standard Operating Procedures (SOP)


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Standard Operating Procedures

(SOP)SOPs shouldaccurately reflecthow routine tasksare performed

Routine inspection,cleaning, maintenance,testing and calibration.

Actions to be taken in

response to equipmentfailure.

Reviewed on regularbasis.


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What happens if a workplace does

not comply with federal GoodLaboratory Practice standards?


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Possible Violations

Falsifying information forpermit, registration

or any required records

Falsifying information related to testing~protocols, ingredients, observations, data

equipment, ect.

Failure to prepare, retain, or submit writtenrecords required by law.


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Consequences of Noncompliance

The FDA states the following consequences ofnoncompliance:

The commissioner will send a written proposalof

disqualification to the testing facility

A regulatory hearing on the disqualification will bescheduled

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 studyitself, or did

not occur at all, then the study may be reinstated at the will

of the commissioner


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Upon Disqualification

If the commissioner finds that the facility showed anoncompliance, any of the grounds after the hearing, then a

final order of noncompliance will be sent to the facility

with explanations

If a testing facility has been disqualified, any studies donebefore of after the disqualification will need to be determinedas essential to a decision (acceptable or not)

If the study is determined unacceptable, then the facility itselfmay need to show that the study was not affected by thenoncompliance 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 isrejected.


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Upon Disqualification The commissioner may notify the public and all interested

persons, including other federal agencies the facility may havecontacted

The FDA may ask the other agencies to consider whether tosupport the facility or not under the disqualification

Civil or criminal proceedings may occur at the discretion ofthe commissioner Fines of up to $50,000 if one knowingly commits crime

and/or 1 year imprisonment~ for registration applicants andproducers

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

Those involved in the distribution or sales will be assessedmore heavy penalties, such as criminal penalties


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Upon Disqualification

The FDA may turn it over to the federal, state or locallaw enforcement

The facilitys sponsor may terminate or suspend thefacility from doing any nonclinical study for a

permit

The sponsor is required to notify the FDA in writing

within 15 working days that the facility is to besuspended or terminated and why


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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


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Good Clinical Practice


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Contents

Glossary

Principles of GCP

IEC/IRB Responsibilities Investigator Responsibilities

Sponsor Responsibilities

Protocols and Amendments

Investigators Brochure

Essential Documents32


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Glossary

Adverse drug reaction (ADR)

Serious Adverse Event (SAE)

Audit

Blinding/masking

Investigator

Protocol

Sponsor

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History of Good Clinical Practice Prior to an actual set of guidelines to follow for good clinical

practice, clinical studies were dangerous and could result in

serous disease, or possibly death.

The Nuremburg Code of 1947 Experiments performed in Germany during WWII opened the eyes of

the world for guidance for clinical testing on humans.

The code did set ethical guidelines, but it lacked legislation to back it

up.

Declaration of Helsinki

In 1964, the World Medical Association established

recommendations guiding medical doctors in biomedical research

involving human subjects. These guidelines influenced national

legislation, but there was no set standard between nations.34

GOOD CLINICAL


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GOOD CLINICAL

PRACTICE

FDA ICH

21 CFR InternationalElectronic Docs.

Inf. Consent

Financial Disclosure

IRBs

IND regs.

glossary

principles

IRBs

Investigator

SponsorEssential Docs


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ICH Guidelines ICH Guidelines are divided into 4 main topics:

Quality Topicsrelate to chemical and pharmaceutical quality

assurance

e.g. Q1 Stability Testing

Safety Topicsrelate to preclinical studies

e.g. S1 Carcinogenicity Testing

Multidisciplinary Topicscross-cutting topics

which dont fit into one of the other categoriese.g. M1 Medical Terminology

Efficacy Topicsrelate to clinical studies in human subjects

e.g. E6 Good Clinical Practice;

e.g. E2A Clinical Safety Data Management:

e.g. E9 Statistical Principles for Clinical Trials 36


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FDA Regulations

21 C.F.R. Part 312, Subpart D (Duties of

Sponsors, Investigators)

21 C.F.R. Part 50 (Informed Consent)21 C.F.R. Part 56 (Institutional Review

Boards)

21 C.F.R. Part 54 (Investigator Financial

Disclosure)

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What is

Good Clinical Practice (GCP) is defined as a

standard for the design, conduct,

performance, monitoring, auditing,recording, analyses and reportingof clinical

trials that provides assurance that the data

and reported results are credible andaccurate, and that the rights, integrity and

confidentiality of trial subjects are

protected38


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Good Clinical Practice (GCP) is aninternational ethical and scientific quality

standard for designing, conducting,recording, and reporting trials that involvethe participation of human patients.

Compliance with this standard providespublic assurance that the rights, safety andwell-being of trial patients are protected and

clinical trial data are credible. 39


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Are mainly focused on the protection of human rightsin clinical trial.

Provide assurance of the safety of the newly

developed compounds. Provide standards on how clinical trials should be

conducted. Define the roles and responsibilities of - Clinical Sponsors, Clinical Research Investigators, Clinical Research Associates, And Monitors.

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Principles of ICH GCP

1. Clinical trials should be conducted in accordance with the ethical

principles that have their origin in the Declaration of Helsinki, and

that are consistent with GCP and the applicable regulatory

requirements.

2. Before a trial is initiated, foreseeable

risks and inconveniences should be

weighed against the anticipated benefitfor the individual trial subject & society.

A trial should be initiated and continued only if the anticipated

benefits justify the risks.

Benefits RISKS

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Principles of ICH GCP Continued

3. The rights, safety, and well-being of the trial subjects arethe most important considerations and should prevailover interests of science & society.

4. The available non-clinical & clinical information on aninvestigational product should be adequate to support the

proposed clinical trial.

5. Clinical trials should be scientifically sound, anddescribe in a clear, detailed protocol.

6. A trial should be conducted in compliance with the

protocol that has received prior IRB (or IEC) approval. 42


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7. The medical care given to, and medical decisions made

on behalf of, subjects should always be the responsibility

of a qualified physician or, when appropriate, of a

qualified dentist.

8. Each individual involved in conducting a trial should be

qualified by education, training and experience to

perform his or her respective tasks.

9. Freely given informed consent should be obtained from

every subject prior to clinical trial participation.43


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10. All clinical trial information should be recorded, handled,

and stored in a way that allows its accurate reporting,

interpretation, and verification.

11. The confidentiality of records that

could identify subjects should be

protected, respecting the privacy

and confidentiality rules in accordance

with the applicable regulatory

compliance.

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12. Investigational products should be manufactured, handled,

and stored in accordance with applicable good

manufacturing practice (GMP). They should be used inaccordance with the approved protocol

13.Systems with procedures that assure the quality of every

aspects of the trial should be implemented.

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Institutional Review Board (IRB),

Independent Ethics Committee (IEC)

A formally designated group that oversees research

involving human subjects.

Approves and disapproves human subject research.

According to the standards of the community or theinstitution, the IRB/IEC may require modifications to a

protocol to ensure patient safety.

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IRB Function

The primary function of an IRB/IEC is to safe guard the

rights ,safety ,and well being of all trial subjects. This isaccomplished by initial, continuing and annual review.

An IRB should consist of members who collectively have

the qualifications and experience to review and evaluatethe science , medical aspects, and ethics of the proposed

trial.

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IRB Members

1.A minimum of five (5) members.

2.One member whose concern is not scientific.

3.One member who has no personal or familial

relationship to the institution or trial site.

4.Any member with a conflict of interest may not

participate in any part of the review or vote (except to

provide requested information).

5.Individuals with special expertise may be invited to assist

with areas of unique or complex nature. These will not be

voting members.

6.A list of IRB/IEC members and their qualifications

should be maintained.48


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IRB/Ethics Committee

All studies must be approved prior to recruiting

participants

IRB must review all documents given to participants

Reporting AEs and Deviations from protocol to the IRB

Maintenance of Records

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Investigator Responsibilities

Adequate Resources

Recruitment

TimeQualified Staff

Facilities

Training

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Medical Care

A qualified MD (or dentist) responsible for

trial-related medical decisionsProvide adequate medical care for AEs or other

significant medical condition

Inform PCP about participation in trial

Make a reasonable effort to ascertain why

participant withdrawals from study

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Compliance with Protocol

Investigator should sign off on protocol

Investigator should not implement deviationsfrom protocol

If deviations occur, they should be documented

and reported at once to the sponsor, the IRB

and other regulatory authorities

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Progress Reports

Written summary of trial

status to the IRB

Written reports to thesponsor or regulatory

authority of any changes

affecting the trial

Safety Monitoring

SAEs should be reported

immediately

AEs should be reportedaccording to sponsor

guidelines

Supply sponsor & IRB

with requested materialson participant deaths

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Premature Termination

or Suspension

Promptly inform trial

subjectsAssure appropriate

therapy & follow-up

Inform sponsor,

regulatory authorities &IRB

Final Reporting

Inform IRB of study

completion & a summary

of the trials outcomeProvide sponsor &

regulatory authorities

with all required reports

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Investigators Brochure

Defined as a compilation of the

clinical and nonclinical data on

the investigational product(s)

that are relevant to the study of

the product(s) in human

subjects.

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Clinical Trial Protocol

General Information

Background Information

Trial Objectives & PurposeTrial Design

Selection & Withdrawal of Participants

Treatment of SubjectsAssessment of Efficacy

Assessment of Safety56


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Quality Assurance & Quality Control

Provide written SOPs

Secures agreement between all partiesData handling

Contract Research Organization (CRO)

Hired by the sponsor to implement trial-related duties

Medical Expertise

Designated medical personnel to advise on trial-related

medical questions and problems

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Trial DesignDesigns CRFs

Planning analyses

Trial Management, Data Handling,Recordkeeping, & Independent Data MonitoringCommittee (DMC)

Qualified personnel to supervise overall conduct of the

study

DMC assesses the progress of the clinical trial

Maintain SOPs for electronic data processing

Inform Investigator of guidelines for record retention58

E ti l D t f th C d t f


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Essential Documents for the Conduct of a

Clinical Trial

Preclinical trial

commencement

During clinical conduct

of trial

After completion or

termination of trial59


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Storage of Essential Documents

Sponsor Rule: refer to studyprotocol

FDA Rule: 2 options

2 years following marketing ofthe drug or,

2 years after IND applicationis withdrawn if drug was notmarketed

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References

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References

http://www.fda.gov/oc/gcp/guidance.htm

http://www.clinicaltrials.gov/

http://www.fda.gov/oc/ohrt/irbs/websites.htmlhttp://ohrp.osophs.dhhs.gov/

http://privacyruleandresearch.nih.gov/

http://en.wikipedia.org/wiki/ICH-GCPHandbook: good laboratory practice (GLP): quality

practices for regulated non-clinical research and

development -2nd ed., WHO Library Cataloguing-in-

Publication Data, 2nd ed., 7,15-20.62
http://www.fda.gov/oc/gcp/guidance.htmhttp://www.clinicaltrials.gov/http://www.fda.gov/oc/ohrt/irbs/websites.htmlhttp://ohrp.osophs.dhhs.gov/http://privacyruleandresearch.nih.gov/http://en.wikipedia.org/wiki/ICH-GCPhttp://en.wikipedia.org/wiki/ICH-GCPhttp://en.wikipedia.org/wiki/ICH-GCPhttp://en.wikipedia.org/wiki/ICH-GCPhttp://privacyruleandresearch.nih.gov/http://ohrp.osophs.dhhs.gov/http://www.fda.gov/oc/ohrt/irbs/websites.htmlhttp://www.clinicaltrials.gov/http://www.fda.gov/oc/gcp/guidance.htmhttp://www.fda.gov/oc/gcp/guidance.htm


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References

OECD Principles of Good Laboratory Practice (as

revised in 1997)". OECD Environmental Health

and Safety Publications(OECD) 1. 1998.http://www.oecd.org/document/63/0,2340,en_264

9_34381_2346175_1_1_1_37465,00.html.

Schneider, K (1983(Spring)). "Faking it: The case

against Industrial Bio-Test Laboratories".AmicusJournal(Natural Resources Defence Council): 14-

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http://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://en.wikipedia.org/wiki/OECDhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://planetwaves.net/contents/faking_it.htmlhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://en.wikipedia.org/wiki/OECDhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.htmlhttp://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.html


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the safety of bisphenol A".J Epidemiol

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February 2011. doi:10.1136/jech.2010.127761.

Webster, Gregory K. et al.(2005). "JALA

Tutorial: Considerations When ImplementingAutomated Methods into GcP".Journal of the

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10(3): 182191. doi:10.1016/j.jala.2005.03.00364
http://en.wikipedia.org/wiki/Digital_object_identifierhttp://dx.doi.org/10.1136/jech.2010.127761http://en.wikipedia.org/wiki/Elsevierhttp://en.wikipedia.org/wiki/Digital_object_identifierhttp://dx.doi.org/10.1016/j.jala.2005.03.003http://dx.doi.org/10.1016/j.jala.2005.03.003http://en.wikipedia.org/wiki/Digital_object_identifierhttp://en.wikipedia.org/wiki/Elsevierhttp://dx.doi.org/10.1136/jech.2010.127761http://en.wikipedia.org/wiki/Digital_object_identifier


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.

Question????

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hank you.