Good laboratory practice or GLP specifically refers to a quality system of management controls

for research laboratories and organizations to try to ensure the uniformity, consistency,
reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) non-
clinical safety tests; from physio-chemical properties through acute to chronic toxicity tests. •
Medicines and Healthcare products Regulatory Agency-UK which defines GLP as: “Good
Laboratory Practice (GLP) embodies a set of principles that provides a framework within which
laboratory studies are planned, performed, monitored, recorded, reported and archived”.

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.

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.

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.

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. GLP was first introduced in New Zealand and
Denmark in 1972, and later in the US in 1978 in response to the Industrial Bio Test Labs
scandal. They discovered a lot fraudulent activities and a lot of poor lab practices.  In the
early 70’s FDA became aware of cases of poor laboratory practice all over the United States.

GLP in OECD (Organization for Economic Cooperation and Development) principles is defined
as “a quality system concerned with the organizational process and the conditions under which
non-clinical health and environmental safety studies are planned, performed, monitored,
recorded, archived and reported”.

HISTORY: The term GLP was first used in New Zealand in 1972. GLP was instituted in US
following cases of fraud generated by toxicology labs in data submitted to the FDA by
pharmaceutical companies. As a result of these findings, FDA promulgated the Good Laboratory
Practice (GLP) Regulations, 21 CFR part 58, on December 22, 1978 (43 FR 59986). The
regulations became effective June 1979. Assure the quality and integrity of safety Nonclinical
laboratory studies. In 1981 an organization named OECD (organization for economic co-
operation and development ) produced GLP principles that are international standard.
GLP also makes sure that data is traceable.  GLP makes sure that the data submitted are a true
reflection of the results that are obtained during the study.

Objectives of GLP 1) GLP makes sure that the data submitted are true reflection of the results
obtained from the studies. 2) GLP makes sure that the data is traceable. 3) Promotes international
acceptance of tests.

Advantages of GLP:
Assures that the data are a true reflection of results obtained from studies.
Preclinical safety and residue safety.
Generation of high quality and reliable test data.
Mutual acceptance of data Increases public confidence.
Shortens the time-to-market for new products.
Disadvantages of GLP
More man power is required.
Expensive process.
Time consuming process

GLP Principles:
Testing facility organization and personnel Storage and retention of records and materials
Reporting of study results Quality assurance program Facilities Apparatus, materials ,reagents
Test systems Test and reference substances Standard operating procedures Performance of study

How to practice GLP?

A.General provisions B. Organization and Personnel C. Facilities D. Equipment E. Testing
facilities operation F. Test and control articles G. Protocol for and the conduct of the study H.
Records and Reports.

A. General provisions
1) It prescribes GLP for conducting non-clinical laboratory studies that support research and
marketing permits of products regulated by FDA. 2) Applicability to studies performed under
grants and contracts. 3) Inspection of the testing facility.

B. Organization and Personnel

1) Organization 2) Personnel 3) Testing facility management 4) Study director 5) Quality
assurance unit
Organization-Functions
1) Identification of quality activities. 2) Dividing the jobs among the personnel. 3) Define the
authority and responsibility of each job and relationship of each job with other jobs. 4)
Coordinate the work of internal departments and outside agencies.

Personnel :
Qualification of personnel: The assumptions is that in order to conduct GLP studies with right
quality a couple of things are important; 1) There should be sufficient . 2) The personnel should
be qualified. • Sponsor: Sponsor: person who initiates & supports nonclinical laboratory study, a
person who submits nonclinical study to FDA or testing facility that initiates & conducts the
study. • Facility management: Responsibilities of facility management is well defined. They
designate a study director, as well as assure quality assurance unit is available, test and control
articles are characterized.
• Study director: He has overall responsibilities for technical conduct safety studies, as well as
interpretation, analysis, documentation and reporting of results. • Quality Assurance unit: The
quality assurance unit (QAU) serves an internal control function. It is responsible for monitoring
each study to assure management that facilities, equipment, personnel, methods, practices,
records, controls, SOPs, final reports (for data integrity), and archives are in conformance with
the GLP.
Testing facility management:
1) A sufficient number of qualified personnel, appropriate facilities, equipment and materials are
available for conductance of the study. 2) Maintenance of records of qualifications, training and
experience of personnel and their job description. 3) Appointment of study director. 4) Quality
assurance program with designated personnel.
Quality Assurance Unit:

1) An individual or a group designated by management to assure that the studies are in

compliance with GLP principles. 2) Monitors the study to assure management that the facilities ,
equipment, personnel, methods, practices, records and controls are in conformance with the
regulations. 3) Maintain the copies of master schedule sheet, protocol and SOPs. 4) Access to
updated study plans and SOPs. 5) Documented verification of compliance of the study with GLP
principles.Inspections to determine the compliance of the study with GLP principles and three
type of inspections are: a) Study based inspections b) Process based inspections c) Facility based
inspections 6) Determines any deviation from the approved protocol and report to SD,PI and
management. 7) Prepare statements to be included in the final report containing dates and types
of inspection.

C. Facilities: 1) General facilities: a) Testing system facilities b) Archive facilities c) Waste

disposal 2) Animal care facilities

General facilities:

Minimum 150sq.feet of floor space and minimum 6 linear feet of usable bench space should be
provide for each analyst. b) Archive facilities- Secure storage and retrieval of study plans, raw
data, final report and specimens to prevent untimely deterioration. c) Waste disposal-
Appropriate collection, storage and disposal facilities and decontamination procedures.
Laboratories should be well ventilated, free of dust, drafts and extreme temperatures.Adequate
degree of separation of different activities. Suitable size, construction and location.
Animal care facilities

1) Located away form testing laboratories preferably in a separate building. 2) Contamination

risk is reduced by “barrier” system ,as well as by providing “clean” and “dirty” corridors . 3)
Separate areas for animals of different species and studies. 4) Separate areas for diagnosis,
treatment and control of laboratory animal diseases. 5) Lightening should be proper as light
intensity and noise level is sufficient. 6) Maintain room temperature, humidity and air changes in
animal quarters.

D. Equipment

1) Appropriate design and adequate capacity. 2) Equipment shall be adequately inspected,

cleaned and maintained. 3) Equipment used for generation, measurement or assessment of data
shall be adequately tested, calibrated and standardized. 4) Log books for each equipment should
be there.

E. Testing Facilities Operation

1) Standard operating procedures(SOPs) 2) Reagents and solutions 3) Animal care

Standard Operating Procedures (SOPs)

1) Written documents specifying procedures for laboratories programs. 2) Testing facility

should have a written SOP approved by management. 3) SOPs should be available
wherever applicable e.g. test and reference items, apparatus, materials and reagents,
record keeping, reporting, storage and retrieval, test systems and quality assurance
procedures. 4) Any deviation from SOP should be authorized by SD and documented in
the raw data. 5) Routine inspection, cleaning, maintenance, testing and calibration. 6)
Actions to be taken in response to routine failure.

Reagents and solutions

1) Reagents used in the operation should be specified in the SOPs. 2) Reagents and
solutions should be labeled. 3) Deteriorated or outdated reagents and solutions should not
be used. 4) Store under ambient temperature.

Animal care

1) SOPs - for housing, feeding, handling and care of animals. 2) Animals should be free of
any disease and if, during the course of study, animals contract a disease then the
diseased animals shall be isolated. 3) Diagnosis, authorization of treatment, description
and date of treatment shall be documented and retained. 4) Animals of different species
shall be housed in separated rooms when necessary. 5) The animal cages, racks and
accessory equipment shall be cleaned and sanitized at appropriate intervals.
F. Test and Control Articles

1) Test and control article characterization 2) Test and control article handling 3) Mixture of
articles with carriers.

Test and control article characterization

1) The identity, strength, purity and composition or other characteristics of test and control
article shall be determined and documented for each batch. 2) Methods of synthesis,
fabrication or derivation shall be documented by the sponsor or the testing facility. 3)
Stability of each test and control article is determined. 4) Storage conditions are maintained
and each storage container shall be labeled by name, chemical abstract number or batch
number.

Test and control article handling

Handling procedures of test and control articles ensures: 1) Proper storage. 2) Minimum risk of
contamination and deterioration or damage. 3) Receipt and distribution of each batch is
documented. 4) Documentation include date and quantity of each batch distributed or returned.

Mixture of articles with carriers

1) Appropriate analytical methods shall be conducted for determination of uniformity of

mixture and concentration of test or control article in mixture. 2) Stability of mixture is
determined. 3) Expiration date should be written on the container.

G. Protocol for and conduct of a nonclinical laboratory study 1) Protocol 2) Conduct of a

nonclinical study

Protocol Contents of protocol 1.Identification 2.Title and statement of purpose 3.Identification

of test(or control) items 4.Names and address of the sponsor, test facility and test site 5.Name of
the study director and other personnel 6.Proposed dates 7.Justification for selection of the test
system 8.Description of the test system 9. Experimental design

Conduct of a nonclinical laboratory study 1) Study shall be conducted in accordance with the
protocol. 2) Information of the specimens should be present on the container to avoid error in
recording and storage of data. 3) All the data generated shall be recorded directly, promptly and
legibly by ink.

H. Records and Reports

1) Reporting of nonclinical laboratory results 2) Storage, retrieval and retention of records and
data
Reporting of nonclinical laboratory study results

Final report shall contain: 1) Information on sponsor and test facility. 2) Experimental starting
and completion dates. 3) Objectives and procedures stated in protocol(including the changes in
protocol). 4) Description of materials and test methods. 5) A Quality Assurance Program
statement. 6) Storage (specimens, reference items, raw data and final report).

Storage, retrieval and retention of records and data

1) Archives should be there for orderly storage and expedient of all raw data,
documentation, protocols, specimens and final reports. 2) Index of materials retained. 3)
Master schedule sheet, copies of protocols and records of Quality Assurance inspections
shall be maintained by QAU. 4) Wet specimens and samples of test and control articles
shall be retained until the quality of preparation affords evaluation. 5) If any study plan is
disposed of before expiry the reason to be justified and documented.

Also it establishes good relationship among the countries. Gives better image of company as a
Quality producer in global market. GLP is a FDA regulation which is accepted and approved as
international standards by OECD to avoid fraud activities of the testing laboratories for
pharmaceuticals to save human and environmental health.

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

If disqualified then:

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.

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

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

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