Good Laboratory Practices

&

Good Clinical Practices

Presented by:-

Mr. Swapnil L. Patil

M.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
History
Objective
Rules and regulation
Noncompliance

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 GLP: GOOD LABORATORY
PRACTICE
 GLP is an FDA regulation.

 Definition: GLP embodies a

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

 GLP is sometimes confused

with the standards of
laboratory safety like
wearing safety goggles. 4
 GOOD LABORATORY
PRACTICE

GLP applies to nonclinical studies conducted

for the assessment of the safety or efficacy of
chemicals (including pharmaceuticals).

GLP helps assure regulatory authorities that

the data submitted are a true.

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 HISTORY
The formal regulatory concept of “Good
Laboratory Practice” (GLP) originated in the
USA in the 1970’s.

The FDA’s publication of Proposed Regulations on

GLP in 1976, with establishment of the Final Rule in
June 1979 (21 CFR 58).

In 1981 an organization named OECD produced

GLP principles that are international standard. 6
WHY WAS GLP CREATED?
In the early 70’s FDA became
aware of cases of ( PLP ) poor
laboratory practice all over the
United States.
FDA decided to do an in-depth
investigation in 40 toxicology labs.
They discovered a lot fraudulent
activities and a lot of poor lab
practices.
Examples of some of these ( PLP )
poor lab practices found were
 Equipment not been calibrated to
standard form , therefore giving
wrong measurements.
 Incorrect/inaccurate accounts of the
actual lab study
 Inadequate plan 7
FAMOUS EXAMPLE
 One of the labs that went under
such an investigation made
headline news.
 The name of the Lab was
Industrial Bio Test. This was a
big lab that ran tests for big
companies such as Procter and
Gamble.
 It was discovered that mice that
they had used to test lotion and
deodorants had developed cancer
and died
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 Industrial Bio Test lab threw the dead mice and covered
results deeming the products good for human use.

Those involved in production, distribution and sales for

the IBT lab eventually served jail time. 9
 OBJECTIVES OF GLP
 GLP makes sure that the data submitted are a
true reflection of 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 Articles
Subpart G: Protocol for and Conduct of a Non-Clinical
Laboratory Study
Subpart J: Records and Reports
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Subpart K: Disqualification of Testing Facilities
 GLP Regulations: Rules and Tools
GLP Regulations (Rules) Documentation (Tools)

ORGANIZATION AND Training records, CVs, GLP training

PERSONNEL
FACILITIES Maintain adequate space/separation
of chemicals from office areas
EQUIPMENT Calibration, logbooks of use, repair,
and maintenance
FACILITY OPERATION Standard operating procedures

TEST, CONTROL, AND Chemical and sample inventory,

REFERENCE SUBSTANCES expiration dates
RECORDS AND REPORTS Timely reporting, storage of raw
data and reports
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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 shall have
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.”

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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, and
experience, or combination thereof,
shall be identified as the study
director. The study director has
overall responsibility for the
technical conduct of the study, as
well 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.”
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 Facilities
58.41 General

“Each testing facility shall be of suitable size and

construction to facilitate the proper conduct of
nonclinical laboratory studies. It shall be designed so
that there is a degree of separation that will prevent
any function or activity from having an adverse effect
on the study.”

 Animal care facilities

 Animal supply facilities
 Facilities for handling test and control articles
 Laboratory operation areas
 Specimen and data storage facilities 16
 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 GLP use. 17
 • Verification (Testing):

Equipment external check of

equipment accuracy (e.g.
check balance accuracy
against weights at
laboratory- no adjustment)
Verification?? ??
• Calibration: equipment is
adjusted based on
comparison to certified or
known reference materials
(e.g. balance adjusted after
Calibration ? Standardization? comparison to certified
weights by trained
professional)
• Standardization:
comparison with similar
equipment (e.g. use two
thermometers of similar
design to compare readings)
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 Protocol , Reports and Records

58.120 Protocol
“Each study shall have an approved written protocol that clearly indicates the
objectives 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 the
protocol”
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 ... shall
be retained.” 19
 Raw Data

Definitions. “’Raw data’ means any

laboratory worksheets, records,
memoranda, notes, or exact copies
thereof, that are the result of original
observations and activities of a study and
are necessary for the reconstruction and
evaluation 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 Data
examples of raw data:-

• Logbooks (to record Question:

temperatures or equipment
use, repair, and maintenance) What happens if you
• Field or laboratory make a mistake?
notebooks
• Forms (for field or laboratory
observations, chain-of-
custody, sample or chemical
receipt)
• Training reports
• Computer printouts
• Recorded data from
automated instruments

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 Standard Operating Procedures (SOP)

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 are
adequate 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
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Standard Operating Procedures
(SOP)
SOPs should
accurately reflect how
routine tasks are
performed
Routine inspection,
cleaning, maintenance,
testing and calibration.
Actions to be taken in
response to equipment
failure.
Reviewed on regular
basis.

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

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 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.

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 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
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 Upon Disqualification…
If the commissioner finds that the facility showed a
noncompliance, 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 done before

of after the disqualification will need to be determined as
essential to a decision (acceptable or not)

If the study is determined unacceptable, then the facility itself

may need to show that the study was not affected by the
noncompliance 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 is
rejected. 27
 Upon Disqualification…
 The commissioner may notify the public and all interested
persons, including other federal agencies the facility may have
contacted
 The FDA may ask the other agencies to consider whether to
support the facility or not under the disqualification
 Civil or criminal proceedings may occur at the discretion of
the commissioner
 Fines of up to $50,000 if one knowingly commits crime
and/or 1 year imprisonment~ for registration applicants and
producers
 Fines up to $5,000 all others~ civil penalty after failing to
improve after a minor violation warning was issued~ only
those involved in testing will be given civil penalties
 Those involved in the distribution or sales will be assessed
more heavy penalties, such as criminal penalties
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 Upon Disqualification…
The FDA may turn it over to the federal, state or local
law enforcement
The facility’s sponsor may terminate or suspend the
facility from doing any non- clinical study for a
permit
The sponsor is required to notify the FDA in writing
within 15 working days that the facility is to be
suspended 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
 Investigator’s Brochure
 Essential Documents

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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.
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 GOOD CLINICAL
PRACTICE
FDA ICH
21 CFR International
• Electronic Docs. • glossary
• Inf. Consent • principles
• Financial Disclosure • IRBs
• IRBs • Investigator
• IND regs. • Sponsor
• Essential Docs

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 ICH Guidelines
 ICH Guidelines are divided into 4 main topics:

 Quality Topics – relate to chemical and pharmaceutical quality

assurance
e.g. Q1 Stability Testing

 Safety Topics – relate to preclinical studies

e.g. S1 Carcinogenicity Testing

 Multidisciplinary Topics – cross-cutting topics

which don’t fit into one of the other categories
e.g. M1 Medical Terminology

 Efficacy Topics – relate 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
 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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Good Clinical Practice (GCP) is defined as a
‘standard for the design, conduct,
performance, monitoring, auditing, recording,
analyses and reporting of clinical trials that
provides assurance that the data and reported
results are credible and accurate, and that the
rights, integrity and confidentiality of trial
subjects are protected’

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Good Clinical Practice (GCP) is an international
ethical and scientific quality standard for
designing, conducting, recording, and reporting
trials that involve the participation of human
patients.

Compliance with this standard provides public

assurance that the rights, safety and well-being of
trial patients are protected and clinical trial data are
credible.
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 Are mainly focused on the protection of human rights
in 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 benefit Benefits RISKS
for the individual trial subject & society.

A trial should be initiated and continued only if the anticipated

benefits justify the risks.
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 Principles of ICH GCP Continued
3. The rights, safety, and well-being of the trial subjects are the most
important considerations and should prevail over interests of
science & society.

4. The available non-clinical & clinical information on an

investigational product should be adequate to support the proposed
clinical trial.

5. Clinical trials should be scientifically sound, and describe in a clear,

detailed protocol.

6. A trial should be conducted in compliance with the protocol that

has received prior IRB (or IEC) approval.
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 Principles of ICH GCP Continued
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.
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 Principles of ICH GCP Continued
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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 Principles of ICH GCP Continued

12. Investigational products should be manufactured, handled,

and stored in accordance with applicable good
manufacturing practice (GMP). They should be used in
accordance 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 the

institution, 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 is
accomplished by initial, continuing and annual review.

•An IRB should consist of members who collectively have

the qualifications and experience to review and evaluate
the 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.

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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
Time
Qualified Staff
Facilities
Training

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 Investigator Responsibilities
Medical Care
A qualified MD (or dentist) responsible for
trial-related medical decisions
Provide 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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 Investigator Responsibilities
Compliance with Protocol
Investigator should sign off on protocol
Investigator should not implement deviations
from 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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 Investigator Responsibilities
Progress Reports Safety Monitoring
Written summary of trial SAEs should be reported
status to the IRB immediately
Written reports to the AEs should be reported
sponsor or regulatory according to sponsor
authority of any changes guidelines
affecting the trial Supply sponsor & IRB
with requested materials
on participant deaths

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 Investigator Responsibilities
Premature Termination Final Reporting
or Suspension Inform IRB of study
Promptly inform trial completion & a
subjects summary of the trial’s
Assure appropriate outcome
therapy & follow-up Provide sponsor &
Inform sponsor, regulatory authorities
regulatory authorities & with all required reports
IRB

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 Investigator’s 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 & Purpose
Trial Design
Selection & Withdrawal of Participants
Treatment of Subjects
Assessment of Efficacy
Assessment of Safety
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 Sponsor Responsibilities
Quality Assurance & Quality Control
Provide written SOPs
Secures agreement between all parties
Data 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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 Sponsor Responsibilities
Trial Design
Designs CRFs
Planning analyses
Trial Management, Data Handling, Recordkeeping,
& Independent Data Monitoring Committee (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 retention
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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 trial
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 Storage of Essential Documents

Sponsor Rule: refer to study

protocol

FDA Rule: 2 options

2 years following marketing of
the drug or,
2 years after IND application
is withdrawn if drug was not
marketed

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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.html
http://ohrp.osophs.dhhs.gov/
http://privacyruleandresearch.nih.gov/
http://en.wikipedia.org/wiki/ICH-GCP
Handbook: 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.

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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_2649_343
81_2346175_1_1_1_37465,00.html. 
Schneider, K (1983(Spring)). "Faking it: The case
against Industrial Bio-Test Laboratories". Amicus
Journal (Natural Resources Defence Council): 14-26.
http://planetwaves.net/contents/faking_it.html. 
. 
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 References
Tweedale, AC (2011). "Uses of ‘Good Laboratory
Practices’ by regulated industry and agencies, and the
safety of bisphenol A". J Epidemiol Community Health
(BMJ Group) Online First: 15 February 2011.
doi:10.1136/jech.2010.127761. 
Webster, Gregory K. et al. (2005). "JALA Tutorial:
Considerations When Implementing Automated
Methods into GcP". Journal of the Association for
Laboratory Automation (Elsevier) 10 (3): 182–191.
doi:10.1016/j.jala.2005.03.003
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 .
Question????

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Thank you……….

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