Good laboratory practice

Rishabh Nagar
M.Pharm (Pharmaceutical
Analysis)
1st year

Department of Pharmaceutical Analysis

I.S.F. College of Pharmacy, Moga
INTRODUCTION ON GLP

Definition-
Good Laboratory Practice (GLP) is
concerned with the organizational process
and the conditions under which laboratory
studies are planned, performed, monitored,
recorded, and reported.

What are GLPs?

In the 1970s, FDA inspections of
nonclinical laboratories revealed that some
HISTORY:-

n GLP is a formal regulation that was created by the FDA (United states
food and drug administration) in 1978.
n Although GLP originated in the United States , it had a world wide
impact.
n Non-US companies that wanted to do business with the United states or
register their pharmacies in the United States had to comply with the
United States GLP regulations.
n They eventually started making GLP regulations in their home countries.
n In 1981 an organization named OECD (organization for economic co-
operation and development ) produced GLP principles that are
international standard.
 WHY WAS GLP CREATED?

In the early 70’s FDA became aware of

Click to edit Master text styles cases of poor laboratory practice all
over the United States.
Second level
● Third level FDA decided to do an in-depth
investigation on 40 toxicology labs.
● Fourth level

● Fifth level They discovered a lot fraudulent activities

and a lot of poor lab practices.

Examples of some of these poor lab

practices found were
1. Equipment not been calibrated to
standard form , therefore giving
wrong measurements.
2. Incorrect/inaccurate accounts of the
actual lab study
3. Inadequate test systems
KEY Dates

1970 1976 FDA GLP proposed

1978 FDA GLP regulations published
1980 1982 OECD GLP published (30 countries
incl. U.S.), UK GLP published, Japanese GLP published
1983 EPA GLP regulations published
1986 FDA GLP revised, European Union GLP Directives
1989 EPA GLP revised
1990 1998 OECD GLPs revised, Canadian PMRA
adopted GLPs
2000 2002 OECD consensus document
2007 EPA may consolidate two parts of EPA GLPs
National Archives and Record
Administration:-

Code of Federal Regulations (CFR)

Title 40 Protection of Environment (laws and regulations of
U.S. EPA)
 Part 160: Good Laboratory Practice Standards, Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA), Subparts A-J
 Part 792: Good Laboratory Practice Standards, Toxic Substances
Control Act (TSCA), Subparts A-J

Note: FIFRA regulates pesticides and TSCA regulates

toxic substances
 The Regulatory Process
of GLPs
Test
Facility Internal audits and inspections (conducted by
Quality Assurance Unit)

Submits Yes!
Data Regulatory Permission to
Sponsor Approve?
Agency Market
(EPA, FDA) Regulated
Product

No!
Permission to
Market Regulated
External audits and
Product Denied
inspections of sponsor and
test facility (conducted by
regulatory agency)
Scope of glp :-

These principles of Good Laboratory Practice

should be applied to testing of chemicals to obtain
data on their properties and/or their safety with
respect to human health or the environment.

These principles of Good Laboratory Practice

should be applied to testing of chemicals to obtain
data on their properties and/or their safety with
respect to human health or the environment.

GLP is a requirement in regulatory non-clinical

Purpose of the glp :-

Improve data quality

Obtain reliable and reproducible data
Obtain comparable quality between countries
Achieve international confidence in study data.
Avoid repetition of studies.
Optimize animal condition.
Shorten the registration time of the drug.
Importance of glp

FDA uses these data to answer questions regarding:-

Ø The toxicity profile of the article.
Ø The observed no adverse effect dose level in the test system.
Ø The risks associated with clinical studies involving humans or animals.
Ø The potential teratogenic, carcinogenic, or other adverse effects of the
article.
Ø The level of use that can be approved.
Type of tests:-

Physico-chemical properties
Toxicological studies designed to evaluate human health effects
Ecotoxicological studies designed to evaluate environmental effects
Ecological studies designed to evaluate environmental chemical fate
(transport, biodegradation, and bioaccumulation)
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; check freezers
FACILITY OPERATION Standard operating procedures

TEST, CONTROL, AND Chemical and sample inventory,

REFERENCE SUBSTANCES track expiration dates, labeling
RECORDS AND REPORTS Timely reporting, storage of raw
data and reports
Elements of glp

1. General provision (58.1)

2. Personnel (58.29)
3. Building and facilities(58.41)
4. Documentation(58.81)
5. Calibration(58.63)
6. Validation of analytical methods
7. Change control
8. Laboratory reagents and solutions(58.83)
9. Control of animal house(58.90)
10. Safety
general provision:-

A drug control laboratory is maintained by the drug regulatory

authority for carrying out the tests & assays required to establish that a
drug conforms to the quality specifications claimed for it.

The contribution of a drug control laboratory to a national drug control

system was described in the twenty-seventh report of WHO expert
committee on specification for pharmaceutical preparations.

A control laboratory can provide effective support for a drug

regulatory agency and its inspection services.

It describes accurately properties of the samples to permit the correct

quality of each drug, and to serve as an adequate basis for any
subsequent administrative and legal action.
Correct assessment of quality of a drug sample is dependent on:-

Ø The submission of a representative sample to the laboratory,

together with a precise indication of why the test is requested.
Ø A correctly planed and meticulously executed analysis; and
Ø A competent evelutoion of the results to determine whether the
sample complies with the specification.
 ● PERSONNEL:-

Medical check up
Health & hygiene
Training of personnel
Job description
Building & facilities

Maintain building & Facilities

Clean Epoxy Flooring and

wall coving - effective
cleaning and no Dirt
accumulation
Arrange to have Sufficient Space
for Storage
Lay out of laboratory:-

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Documentation:-

The availability of a complete set of SOP necessary to govern all the pertinent activities
and procedures in the test facility is an absolute prerequisite.
They define how to carry out protocol specificities.
Some of the key SOPs which need to be addressed include:-
Ø The samples handling and accountability.
Ø Receipt, identification, storage, method of sampling of test articles.
Ø Record keeping, reporting, storage and retrieval of data.
Ø Operating of technical audit personnel in conducting and reporting audits , inspection,
reports, reviews.
Ø Routine inspection of cleaning maintenance, testing, calibration of equipment.
Ø Calibration management.
Ø Validation of analytical methods.
Change control procedure.
Animal room preparation & animal care.
Storage, maintenance and traceability of microbial cultures.
Storage, use of reference standards and reagents.
Laboratory waste handling.
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)
Calibration :-

 Calibration: equipment is adjusted based on

comparison to certified or known reference materials
(balance adjusted after comparison to certified weights
by trained professional)

 Verification (Testing): external check of equipment

accuracy (check balance accuracy against weights at
laboratory- no adjustment
Validation of analytical methods:-

o All analytical methods, particularly none –standard &

in-house test method must be validated by a procedure
given below.
o All analytical equipment must be appropriately
qualified before method validation.
o The validation methodology must clearly documented
& should include:-
ü Selectivity & specificity.
ü Range.
ü Linearity.
ü Robustness
ü
 and appropriate data to verify that results are as accurate and reliable as the
established method.

CHANGE CONTROL

All changes in equipment, test environment, test method, services, system

or location that may affect reproducibility, accuracy or standards must be
formally requested, documented and accepted.
Laboratory reagents and solutions :-

о Their must be written procedures in place for the

handling of reagents and preparation of standards
solutions.
о All reagents and solutions in the laboratory areas shall be
labeled to indicate identity,concentration, storage
requirements, expiration date.
о Deteriorated or outdate reagents and solutions shall not
be used. Good laboratory technique has always included
proper labeling of reagents & solutions .
о SOP should be maintained for the storage at ambient
room temperature unless otherwise indicated on the label.
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
CONTROL ON ANIMAL HOUSE :-

o SOPs for housing, feeding, care, handling.

o Newly-received animals; isolated and health status determined
animals free of disease before and during study.
o If diseased during study, treatment should not interfere with study
and be documented.
o Warm-blooded animals if removed from home cage; identified (ID
on outside of housing unit)
o Different species in separate rooms when necessary. Same
species/different studies; ideally separate rooms
o Cages, racks; cleaned/sanitized(appropriate interval.)
o Feed and water analyzed periodically for contaminants that may
affect study should be documented.
o Bedding should not interfere with study.
o Pest control materials should not interfere with study.
SAFETY:-

o People who work in scientific laboratories are exposed to many

kind of hazards so safety of people should be considered.
o The design and construction is the first instance of building safety
features in the laboratory.
o Laboratory must be equipped with:-
Ø Adequate fire extinguishers.
Ø Personnel protecting equipment.
Ø Eye wash fountains & first aid kits.
o The design should facilitate the change of street clothes and
footwear by the specific laboratory personnel.
o No food, beverage or cosmetic product should be allowed in the
laboratory or chemical storage area at any time.
TRAINING :-

Test facility management must provide training for all personnel whose
duties involve the conducting of tests and analysis.
Training appropriate to the duties assigned to them.
A particular SOP should be documented for a training program.
The records of their educational and professional qualification, training
undergone, skills and experience shall also be maintained.
Quality audit:-

The QA program or self audit should be carried out by an individual or

by individuals who are designated by & directly responsible to the
facility manager and who are thoroughly familiar with the test
procedures
These individual must not be involved in the conduct of the study/ test
being assured.
The responsibilities of these QA / audit personnel include:-
o Maintain a copy of all approved test method / study plan/ SOP use
in test facilities.
o Verify that test methods/study plans contain the information
required for compliance with the principles of GLP.
Conduct audits/ inspections to assure that tests are conducted in
accordance with these principles of GLP.
Inspections can be of three types :-
A. Study / test based inspections
B. Facility based inspection
C. Process based inspection
Ø. Document and retain records of all inspections
Ø. Inspect the final repots to confirm accurately and completely
described method procedures.
Management review:-

Management of a test facility as the ultimate

responsibility for ensuring that the facility as a
whole operate in compliance with the GLP
principles.
Quality audit and Quality assurance program
which is independent of the actual conduct of
test/ study and is designed to assure the test
facility management of compliance with these
principles of GLP.
references:-

§ http://www.sjsu.edu/faculty/chem55/55glpou
t.htm
§ http://www.labcompliance.com/tutorial/glp/d
efaul
§ UGA Office of the Vice President for Research
§ Wikipedia
§ Code of Federal Regulations (CFR)
•
EPA GLP Regulations
• FDA GLP Regulations
• USDA- Pesticide Data Program (PDP) Standard
Operating Procedures
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