GOOD LABORATORY

PRACTICE (GLP)

Tri Wibawa
Dept of Microbiology
Faculty of Medicine
Role of Laboratories in Medical Product
Development Process
• Research Laboratories
• Discovery & development of new drugs /
device/therapy
• Fundamental research/mechanisms of
diseases
• Animal Laboratories
• In vivo studies
• Animal models / preclinical studies
• Safety and sensitivity testing
• Calibration Laboratories
• Equipment & device calibration
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• Non clinical Testing & Analytical Laboratories
– Toxicology
– Mutagenicity
– Safety pharmacology
– Bioequivalence / bioavailability
– pharmacokinetics

• Clinical Testing & Analytical Laboratories

– Screening & Diagnosis (Enrolment : inclusion criteria exclusion)
– Quality control
– Trial monitoring : Verify effects of drugs clinical efficacy
– Monitoring of adverse effects safety
– Data analysis
– Verification
• Manufacturing Laboratories
– Production of drugs, cell-based therapy, plasma products, medical
device
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 Why do we need
STANDARDS?
• Laboratories are required to be Accredited or Compliant
to a set of defined STANDARDS

• Standards are documented agreements containing

technical specifications or other precise criteria used
consistently as rules, guidelines and definitions of
characteristics to ensure that material, products, process
and services are fit for its claimed purpose.

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 Standards Available
• International Organisation of Standardisation (ISO)
• Good Clinical Practice (GCP)
• Good Manufacturing Practice (GMP)
• Good Distribution Practice (GDP)
• Good Tissue Practice (GTP)
• Good Clinical Laboratory Practice (GLCP)
• OECD Principle of Good Laboratory Practice (OECD
GLP)

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 What is GLP?
• Organisation for Economic Co-operation and
Development (OECD) Principles:
“a quality system concerned with the
organisational process and the conditions under
which non-clinical health and environmental
safety studies are planned, performed,
monitored, recorded, archived and reported.”
sistem jaminan mutu yang berkaitan dengan proses organisasi dan kondisi
di mana penelitian kesehatan non-klinis dan keamanan lingkungan
direncanakan, dilakukan, dimonitor, dicatat, diarsipkan dan dilaporkan
 The purpose of the Principles of
Good Laboratory Practice
• To promote the development of quality test
data and provide a tool to ensure a sound
approach to the management of laboratory
studies, including conduct, reporting and
archiving
• The Principles may be considered as a set of
standards for ensuring the quality, reliability
and integrity of studies, the reporting of
verifiable conclusions and the traceability of
data.
 DRUG DEVELOPMENT STAGES
QPBR GLP GCP GCP

QPBR=Quality Practices in
Basic Biomedical Research GMP
 The GLP Principles apply only to
studies which :
• are non-clinical, i.e. mostly studies on animals
or in vitro, including the analytical aspects of
such studies;
• are designed to obtain data on the properties
and/or the safety of items with respect to
human health and/or the environment;
• are intended to be submitted to a national
registration authority with the purpose of
registering or licensing the tested substance or
any product derived from it.
 GLP Requirements
• GLP requirements for non-clinical laboratory studies
conducted to evaluate drug safety cover the following
classes of studies:
– Single dose toxicity
– Repeated dose toxicity (sub-acute and chronic)
– Reproductive toxicity (fertility, embryo-foetal toxicity and
teratogenicity, peri-/post natal toxicity)
– Mutagenic potential
– Carcinogenic potential
– Toxicokinetics (pharmacokinetic studies which provide systemic
exposure data for the above studies)
– Pharmacodynamic studies designed to test the potential for
adverse effects (Safety pharmacology)
– Local tolerance studies, including phototoxicity, irritation and
sensitisation studies,
 GLP Implementation
• GLP Principles are independent of the
site where studies are performed. They
apply to studies planned and conducted in
a manufacturer’s laboratory, at a contract
or subcontract facility, or in a university or
public sector laboratory.
• GLP is not directly concerned with the
scientific design of studies
 GLP in Research Institutions.

• GLP Principles help

to define and
to
standardize: eliminate
– Planning
– Performance many
– Recording
– Reporting
sources
– Monitoring of error
– Archiving
 Why Were the GLPs
Mandated?
• In the 1970s, numerous cases of
laboratory malpractice surfaced in toxicity
testing of food and drugs in the U.S.
• FDA inspectors found inaccurate, sloppy,
and fraudulent research studies
• Became a public safety issue
 Why Do We Need GLPs?
• Everyone makes mistakes
• Mistakes cost $$$
• Increasing the quality of an
operation is good for business and
science
 GLP Principles
GLP principles are a good idea even if you are
not required to comply with the regulations.
• Say What You Do (with written standard
operating procedures)
• Do What You Say (follow the procedures)
• Be Able to Prove It (with good record keeping)
 The Regulatory Process
Before GLPs – Few “checks and balances”
Test
Facility Inaccurate, sloppy, and fraudulent science???

Submits Yes!
Sponsor Data Regulatory Permission to
Approve?
Agency Market Regulated
Product

Poor Management No!

Practices ???? Permission to
Market Regulated
Product Denied

Would you want the Regulatory Agencies to issue a permit to

manufacture of a drug based on sloppy research? Probably not!
 The Regulatory Process
After GLPs
Test
Facility
Internal audits and inspections (conducted by
Quality Assurance Unit)

Submits Yes!
Sponsor Data Regulatory Permission to
Approve?
Agency Market Regulated
Product

No!
Permission to
Market Regulated
External audits and Product Denied
inspections of sponsor and
test facility (conducted by
regulatory agency)
 FDA GLP Compliance
Required:
Non-clinical safety studies for the development of
food additives and drugs (before a marketing permit
is issued)
Regulated products: Pharmaceuticals, cosmetics,
food & color additives, human medical devices

Note: “non-clinical” refers to safety testing in animals,

plants, or microorganisms (not humans)
 EPA GLP Compliance
Required:
Field and laboratory studies of pesticides (before a
marketing permit or application for research is
issued)
Regulated products: Pesticides and other
substances that could spread during agricultural
practice
 History
• (GLP) originated in the USA in the 1970s
– Concerns about the validity of non-clinical
safety data submitted to the Food and Drug
Administration (FDA) in the context of New
Drug Applications (NDA).
– The GLP regulations provided the basis for
assurance that reports on studies submitted
to FDA would reflect faithfully and completely
the experimental work carried out.
– US Environmental Protection Agency (EPA)
• The Organisation for Economic Co-
operation and Development (OECD)
principles of GLP:
– To avoid non-tariff barriers to trade in
chemicals
– To promote mutual acceptance of non-clinical
safety test data
– To eliminate unnecessary duplication of
experiments.
• Internationally, compliance with GLP is a
prerequisite for the mutual acceptance of
data;
• Different countries or regulatory authorities
accept laboratory studies from other
countries provided they comply with the
OECD GLP Principles.
THE FUNDAMENTAL POINTS OF
Good Laboratory Practice
• Resources: Organization, personnel, facilities
and equipment;
• Characterization: Test items and test systems;
• Rules: Protocols, standard operating procedures
(SOPs);
• Results: Raw data, final report and archives
• Quality Assurance: Independent monitoring of
research processes.
 RESOURCE
• Organization and Personnel
– The research organisation
– Responsibilities of the research personnel
– The number of personnel available
– The qualifications of staff
– Internal and external training
 RESOURCE
• Facilities and
equipment
– Sufficient and adequate to
perform the studies.
– Spacious enough
– Equipment: working order;
validation/qualification,
calibration, maintenance,
records and history.
 Equipment
• Was the equipment
functioning properly?
Who performed the
work, what was the
date, and what specific
parameters did they
use?
• What was there a
problem? How was the
problem fixed?
 Use Logbooks
AGILENT GAS CHROMATOGRAPH SERIES: 6890n VT#0000322580

DATE NAME PROJECT SAMPLE DETECTO COLUMN OVEN INLET DET GAS mL/min ROUTINE PROBLEM
MATRIX R TYPE TYPE/ SIZE TEMP °c TEMP °c TEMP °c SERVICE (#) (#)

9/13/07 John VCE07- Water µECD RTX-5 (30 60-275°C 250°C 350°C He-carrier, Replaced He N/A
Smith 020 #8128/ m x 0.25 2.3 mL/min, gas - VAC052
(lab µECD mm x 0.25 N2 makeup 9/13/07
tech) #5663 µm) J.E.S.
(dual
column)

9/14/07 Sally VCE07- Plant µECD RTX-5 (30 90-275°C 250°C 350°C He-carrier, N/A Power
Jones 021 Tissue #8128/ m x 0.25 2.3 mL/min, outage
(lab µECD mm x 0.25 N2 makeup caused GC
tech) #5663 µm) shutdown
(dual
column)

9/17/07 Sally Standards N/A NPD RTX-OPP 60-275°C 225°C 300°C He-carrier, New glass N/A
Jones only (30 m x 1.0 mL/min, insert & gold
(lab 0.25 mm x H2/Air det. seal 9/17/07
tech) 0.25 µm) gases S.J.

• Record all pertinent operating parameters

• Take the time to record routine service and how
problems were resolved (it may help if/when the
same problem arises!)
 CHARACTERISATION
• Essential to know as much as possible
about the materials used during the study
• Test item: identity, potency, composition,
stability, impurity profile
• Animal (which is very often the case):
strain, health status, normal biological
values, group assignment, etc.
 Reagents and Solutions
General expiration guidelines:
• Dry reagents: 5 years (unless reevaluated)
• Solvents: 1 year from date opened or 2 years
from date received
• Solutions: Use the earliest date of components
in the solution or no longer than 6 months

Question: Which takes precedence: the

manufacturer’s expiration date or expiration date
as stated in the facility SOPs?
Answer: Whichever is earliest!
 Use Labels
• Clearly label chemicals CHEMICAL LABEL

and solution containers CHEMICAL___ ____________ ________

CHEM ID#______________________________ _
DATE RECEIVED:___________________________
• Make sure that the DATE OPENED: ____________________________

expiration date and EXPIRATION DATE__ _ _______STORAGE______

storage requirements are

included on the label SOLUTION LABEL
CONCENTRATION_____________________

• If a solution, what date SOLUTION____________________________

FROM CHEM ID#_____________________
was it prepared? DATE PREPARED_____________________
EXPIRATION DATE______ STORAGE______
 RULES
• Protocol or study plan
– Protocol outlines the design and conduct of
the study
– The protocol must be approved by the Study
Director, by dated signature, before the study
starts
– Alterations to the study design can only be
made through formal amendment procedures.
 RULES
• Written Procedures
– The details of all routine procedures are
described in Standard Operating Procedures
(SOPs)
– SOPs contribute to reducing bias in studies
– To facilitate comparison of results between
studies
– To be able to exactly reconstruct a study
– Procedures cannot be fixed for all time 
reviewed and revised.
 RESULTS
• Raw Data
– The original data collected during the conduct
of a procedure
– Also document the procedures and
circumstances under which the study was
conducted
– The results of the experiment upon which the
conclusions of the study will be based.
– Some of the raw data will be treated
statistically, while others may be used directly
What happens if you
make a mistake?

Do not obscure original data!! Instead, draw a

single strikeout, then add reason code, initials,
and date of change. (Preserve the original data).
 RESULTS
• Documentation
• Record data using permanent ink (never pencil)
• Date and sign every entry (who is responsible?)
• Keep records in “real time” (no catching up later)
• No rewrites, need original entries (reduces
transcription errors)

Documentation is important in all

sorts of situations!!
 RESULTS
Examples of raw data:
• Logbooks (to record temperatures or equipment use,
repair, and maintenance)
• Field or laboratory notebooks
• Forms (for field or laboratory observations, chain-of-
custody, sample or chemical receipt)
• Training reports
• Computer printouts
• Recorded data from automated instruments
 RESULTS
• Study Report
– Is the responsibility of the Study Director
– He/she must ensure that it describes the
study accurately
• Archives
– Safekeeping for long periods of time without
loss or deterioration
– Allows quick retrieval
– Restricted access
 QUALITY ASSURANCE
• is a team of persons charged with
assuring management that GLP
compliance has been attained in the test
facility as a whole and in each individual
study.
• QA must be independent of the
operational conduct of the studies
• Functions as a “witness” to the whole
preclinical research process.