WJPR 6039

www.wjpr.net Vol 5, Issue 4, 2016.
Davinder et al. World Journal of Pharmaceutical Research
GOOD LABORATORY PRACTICE (GLP): AN INCLUSIVE REVIEW
Dr. Kaushal Kishore Chandrul and *Davinder Singh
School of Pharmaceutical Sciences, Shri Venkatashwara University, Ajroula, Utterpardesh,
India.
ABSTRACT
GLP is an official regulation that was created by the FDA in 1978.
The OECD (Organisation for Economic Co-operation and
Development) Principles of Good Laboratory Practice were first
created by an Expert Group on GLP set up in 1978 under the
Special Programme on the Control of Chemicals. The GLP
regulations that are accepted as international standards for non-clinical
laboratory studies published by the US Food and Drug Administration
in 1976 supplied the basis for the work of the Expert Group, which was
guided by the United States and consisted experts from the following
countries and organizations: Australia, Austria, Belgium, Canada,
Denmark, France, the Federal Republic of Germany, Greece, Italy,
Japan, the Netherlands, New Zealand, Norway, Sweden, Switzerland,
the United Kingdom, the United States, the Commission of the European Communities, the
World Health Organization and the International Organization for Standardization.
Good laboratory practice is an FDA regulation. Good laboratory practice constitutes of a set
of principles that provides a framework within which laboratory studies are planned
performed, monitored, reported and archived. Good laboratory practice is a formal
regulation that was created by the FDA (United states food and drug administration) in 1978.
GLP makes sure that the data submitted are a true reflection of the results that are
obtained during the study. It also makes sure that data is traceable and promotes
international acceptance of tests. The Food and Drug Administration (FDA) good
laboratory practice (GLP) inspections in fiscal year 2003 increased significantly at a level of
71% over the previous year. A review and analysis of recently issued FDA warning letters
for nonclinical laboratory studies found that the two major GLP compliance deficiencies
World Journal of Pharmaceutical Research
SJIF Impact Factor 6.805
Volume 5, Issue 4, XXX-XXX. Review Article ISSN 2277– 7105
*Corresponding Author
Davinder Singh
School of Pharmaceutical
Sciences, Shri
Venkatashwara
University, Ajroula,
Utterpardesh, India
davindersingh2996@gmail.com
Article Received on
22 Feb 2016,
Revised on 11 March 2016,
Accepted on 02 April 2016
DOI: 10.20959/wjpr20164-6039

were study director responsibility and authority (21 CFR §58.33) and the quality
assurance unit (21 CFR §58.35). This article reviews the background of the GLP regulations,
the FDA GLP inspection program, the importance of interpreting the GLP regulations, the
use of published FDA references to ensure the correct and effective interpretations of the
regulations and the specific interpretations of the GLP requirements for the study director
and quality assurance unit. Since June 20, 1979, the agency has been asked many questions
on the Good Laboratory Practice regulations (GLPs, 21 CFR 58). In accordance with
agency procedures, responses have been prepared and copies of the associated
correspondence have been filed in the Dockets Management Branch (HFA-305). The
responses have also been provided to the bioresearch monitoring program managers and to
the district offices in order to ensure consistency of interpretation and equity of program
operation. Unfortunately, the numerous filed correspondence contain many repeat questions
that are not categorized to relate to the specific GLP subpart and section. On occasion, the
answers appear to be somewhat cryptic. These disadvantages serve to limit the utility of the
correspondence as advisories. The WHO/TDR effort to promote the development of
therapeutic substances against tropical diseases and the conduct of studies in DECs is a
matter of high priority. For studies to be readily accepted by regulatory authorities
world-wide GLP implementation in laboratories conducting non-clinical safety studies is of
major importance. Part of achieving this goal in regions where there is limited knowledge
of and experience with formal quality concepts like GLP is to promote ―technology‖ or
―knowledge transfer‖, through the training of scientists, thus enabling them to work in
compliance with these standards. Therefore, WHO/TDR is actively promoting training
courses designed to provide an understanding of the concepts of GLP and to facilitate the
practical implementation and application of these principles. The WHO/TDR GLP training
course in GLP is seen as an enabler aiming to assist institutes in Disease Endemic
Countries (DECs) to reach GLP compliance thus allowing them to increase the international
credibility of their data and results. Therefore, this GLP training contributes pertinently to
capacity building in DECs which is one of the specific aims of WHO/TDR.
KEYWORDS: Good Laboratory Practice, Disease Endemic Countries.
INTRODUCTION
Good laboratory practices used for conducting nonclinical laboratory studies that support or
are intended to support applications for research or marketing permits for products regulated
by the Food and Drug Administration, including food and color additives, animal food

additives, human and animal drugs, medical devices for human use, biological products, and
electronic products. Compliance with this part is intended to ensure the quality and
integrity of the safety data filed pursuant to sections 406, 408, 409, 502, 503, 505, 506,
510, 512-516, 518-520, 721 and 801 of the Federal Food, Drug, and Cosmetic Act and
sections 351 and 354-360F of the Public Health Service Act.
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. Studies covered by Good Laboratory Practice also include work conducted in
field studies. These data would be developed for the purpose of meeting regulatory
requirements. Good Laboratory Practice (GLP) is concerned with the organizational process
and the conditions under which laboratory studies are planned, performed, monitored,
recorded, and reported as well as Test facility of laboratories means the persons, premises,
and operational unit(s) that are necessary for conducting the study and Director has the
individual responsible for the overall conduct of the study conducted Quality Assurance
Programme on internal control system designed to ascertain that the study is in compliance
with these Principles of Good Laboratory Practice. Laboratory have Standard Operating
Procedures (SOPs) written procedures which describe how to perform certain routine
laboratory tests or activities normally not specified in detail in study plans or test guidelines.
Definitions: The quality is the capability to systematically produce the same product to meet
the same specifications and time after time. GLP was altered to protect the integrity and
quality of laboratory data used to back up a product application. The definition of the term
―Good Laboratory Practice‖ itself, which identifies GLP as ―a quality system related with the
organizational process and the conditions under which non-clinical health and
environmental safety studies are planned, performed, monitored, recorded, archived and
reported.‖ can be considered as an example of a brief and accurate definition. GLP
describes good practices for non-clinical lab studies that support research or marketing
approvals for FDA-regulated products.
Applicability to studies performed under grants and contracts: When a sponsor
conducting a nonclinical laboratory study intended to be submitted to or reviewed by the
Food and Drug Administration utilizes the services of a consulting laboratory,
contractor, or gaurantee to perform an analysis or other service, it shall notify the

consulting laboratory, contractor, or guarantee that the service is part of a nonclinical
laboratory study that must be conducted in compliance with the provisions of this part.
Accreditation can be especially useful to suppliers. Often accreditation schemes monitor
members’ implementation of national and international standards thus, a supplier or
manufacturer’s accreditation certificate may signify to the customer the satisfactory
implementation of a standard in addition to other aspects of accreditation. It is recommended
that suppliers seek membership, where feasible and/or appropriate, in national accreditation
schemes. Although accreditation is a useful complementary tool to support compliance
with the GLP Principles, it is not an acceptable alternative to GLP compliance nor will it
lead to international recognition in the context of meeting the requirements for the mutual
acceptance of data as set out in the OECD Council Acts. (OECD, 1998).
The principles of good laboratory practice: Good Laboratory Practice is based the
following described basic principles:
1. The Management
There should be an unique identification for the study and all of its parts. All original
observations in a study should be at once clearly and legibly recorded. The recording should
be permanent and corrections should be made so as not to obscure the original entry; for all
corrections the respective reasons have to be provided. All records should be in the form
of bound notebooks or on continuously numbered sheets. All entries and corrections to
them should be dated and initiated. Records related to the test system itself should be
gathered and preserved. Specimens should be clearly identified so as to allow full
traceability. At the end of a study, all raw data should be assembled, catalogued and
archived. Archiving should support for secure storage of all raw data, samples and
specimens, together with any other documents such as study plan and study report. The
Quality Assurance; The Study Director; and The National Compliance Monitoring
Authority. All of them serve important functions in the concordancy of performing and
monitoring safety studies and it should be kept in mind that all of them are required for GLP
to achieve quality data.
2. Organization and Personnel
Ensure that qualified personnel, appropriate facilities, equipment and materials are
available maintain a record of the qualifications, training, experience and job description for

each professional and technical individual ensure that personnel clearly understand the
functions they are to perform and, where necessary, provide training for these functions
guidelines for health and safety precautions are applied according to national and
international regulations used appropriate Standard Operating Procedures are established
and followed ensure that there is a Quality Assurance Programme with designated personnel
where appropriate, agree to the study plan in conjunction with the sponsor ensure that
amendments to the study plan are agreed upon and documented; maintain copies of all study
plans; maintain a historical file of all Standard Operating Procedures; for each study ensure
that a sufficient number of personnel is available for its timely and proper conduct; for
each study designate an individual with the appropriate qualifications, training, and
experience as the Study Director before the study is initiated. If it is necessary to replace a
study director during a study, this should be documented ensure that an individual is
identified as responsible for the management of the archives.
3. 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. The quality
assurance unit shall maintain a copy of a master schedule sheet of all nonclinical
laboratory studies conducted at the testing facility indexed by test article and containing
the test system, nature of study, date study was initiated, current status of each study,
identity of the sponsor, and name of the study director. Maintain copies of all protocols
pertaining to all nonclinical laboratory studies for which the unit is responsible. Inspect each
nonclinical laboratory study at intervals adequate to assure the integrity of the study and
maintain written and properly signed records of each periodic inspection showing the
date of the inspection, the study inspected, the phase or segment of the study inspected,
the person performing the inspection, findings and problems, action recommended and taken
to resolve existing problems, and any scheduled date for re-inspection.
4. Facilities
The minimum required facilities should be of suitable size, construction and location to
meet the requirements of the study and minimize disturbances that would interfere with the

validity of the study. The design of the test facility should provide an adequate degree of
separation of the different activities to assure the proper conduct of each study.
5. Animal care facilities
There shall be storage areas, as needed, for feed, bedding, supplies, and equipment.
Storage areas for feed and bedding shall be separated from areas housing the test systems
and shall be protected against infestation or contamination. Perishable supplies shall be
preserved by appropriate means.
a. A testing facility shall have a sufficient number of animal rooms or areas as needed to
assure proper, Separation of species or test systems, isolation of individual projects,
quarantine of animals, and routine or specialized housing of animals.
b. A testing facility shall have ensure isolation of studies being done with test systems
or test and control articles known to be biohazardous, including volatile substances, aerosols,
radioactive materials, and infectious agents.
c. Separate areas shall be provided, as appropriate, for the diagnosis, treatment, and control
of laboratory animal diseases. These areas shall provide effective isolation for the housing
of animals either known or suspected of being diseased, or of being carriers of disease,
from other animals.
d. When animals are housed, facilities shall exist for the collection and disposal of all
animal waste and refuse or for safe sanitary storage of waste before removal from the testing
facility. Disposal facilities shall be so provided and operated as to minimize vermin
infestation, odours, disease hazards, and environmental contamination.
6. Facilities for handling test and control articles
Prevent contamination there should be separate areas for receipt and storage of the test and
reference substances, and mixing of the test substances with a vehicle. Storage areas for the
test substances should be separate from areas housing the test systems and should be
adequate to preserve identity, concentration, purity, and stability, and ensure safe storage for
hazardous substances.
As necessary to prevent contamination or mixups, there shall be separate areas for:
(1) Receipt and storage of the test and control articles.
(2) Mixing of the test and control articles with a carrier, e.g., feed.
(3) Storage of the test and control article mixtures.

(b) Storage areas for the test and/or control article and test and control mixtures shall be
separate from areas housing the test systems and shall be adequate to preserve the identity,
strength, purity, and stability of the articles and mixtures.
7. Laboratory operation areas: Facilities: Buildings and Equipment
Test facilities should be of suitable size, construction and location to meet the requirements
of the study and to minimise disturbances that could interfere with the study. They should
be designed to provide an adequate degree of separation of the diverse elements of the study.
The purpose of these requirements is to ensure that the study is not compromised because of
inadequate facilities. It is important to remember that fulfilling the requirements of the study
does not necessarily mean providing ―state of the art‖ constructions,but carefully considering
whether the objectives of the study can be achieved using the facilities available.Separation
ensures that disturbances are minimised and that different activities do not interfere with one
another or adversely affect the study. This can be achieved by: Physical Separation;
e.g.walls, doors, filters or separate cabinets or isolators. In new buildings, or those recently
renovated, separation will be part of the design.
8. Specimen and data storage facilities
Test items must be stored under closely controlled environmental conditions. Only
designated staff should have access to the material. The stores should be kept locked when
not in use. Separate areas should be available for storage at different temperatures such as at
ambient temperature, at +4°C and at -20°C. The storage of test items is arranged to
minimise the risk of any cross contamination between items and containers. Where possible,
the primary containers are housed within an outer container (secondary packaging) in case of
breakage or spillage within the store. On arrival at the test facility, a sample of the batch of
test item is taken and stored in a separate container.
9. Equipment design
Equipment used in the generation, measurement, or assessment of data and equipment
used for facility environmental control shall be of appropriate design and adequate capacity
to function according to the protocol and shall be suitably located for operation, inspection,
cleaning, and maintenance. Equipment, including validated computerised systems, used for
the generation, storage and recovery of data, and for controlling environmental factors
relevant to the study should be suitably located and of appropriate design and adequate
capacity. Equipment records should include: name of the equipment and manufacturer,

model or type for identification, serial number, date equipment was received in the
laboratory, copy of manufacturers operating instruction(s). Equipment used in a study should
be periodically inspected, cleaned, maintained, and calibrated according to Standard
Operating Procedures. Records of these activities should be maintained. Calibration should
be traceable to national or international standards of measurement. Instrumentation
validation is a process necessary for any analytical laboratory. Data produced by ―faulty‖
instruments may give the appearance of valid data. The frequency for calibration,
re-validation and testing depends on the instrument and extent of its use in the laboratory.
Chemicals, reagents, and solutions should be labelled to indicate identity, expiry date and
specific storage instructions. Information concerning source, preparation date and stability
should be available. The expiry date may be extended on the basis of documented evaluation
or analysis. If a mistake is made, original data should not be obscured. Instead of this, a
single strike out should be drawn and a reason code should be added, later the date should
be changed. Whenever an instrument’s performance is outside the ―control limits‖ reports
must be discontinued. Equipment used for the generation of physical/chemical data should
be suitably located and of proper design and adequate capacity. The integrity of the
physical/chemical test systems should be ensured. Appropriate conditions should be
established and maintained for the storage, housing, handling and care of biological test
systems, in order to ensure the quality of the data. Standardization, calibration, and
verification are the definitions which have particular importance for the equipments. The
difference between those should be well understood and performed by the laboratory
personnel: Verification is the external check of equipment accuracy. It is the check balance
accuracy against weights at laboratory. There is no adjustment. In calibration equipment is
adjusted based on comparison to certified or known reference materials. The balance is
adjusted after comparison to certified weights by trained professional. Standardization is
made by comparison with similar equipments, such as using two thermometers of similar
design to compare readings. While monitorizing the study laboratory staff should always
have the following questions on mind: Was the equipment functioning properly? Who
performed the work, what was the date, and what specific parameters did they use? Was
there a problem? How was the problem fixed? Were there any problems with the reagents
and solutions? Laboratory equipment should routinely be maintained and calibrated. The
GLP Principles do not suggest or require any specific time intervals for such activities.
Cleaning and maintenance intervals may be different from one type of equipment to the
other, and such intervals may as well depend on the frequency of use or the workload

imposed on the respective equipment. On the other hand the question of the correct
frequency of such activities should be considered as a scientific one, calling for the expert
judgement of the responsible scientists.
10. Maintenance and calibration of equipment
(a) Equipment shall be adequately inspected, cleaned, and maintained. Equipment used for
the generation, measurement, or assessment of data shall be adequately tested, calibrated
and/or standardized.
(b) The written standard operating procedures required under 58.81(b)(11) shall set forth
in sufficient detail the methods, materials, and schedules to be used in the routine inspection,
cleaning, maintenance, testing, calibration, and/or standardization of equipment, and shall
specify, when appropriate, remedial action to be taken in the event of failure or
malfunction of equipment. The written standard operating procedures shall designate the
person responsible for the performance of each operation.
(c) Written records shall be maintained of all inspection, maintenance, testing, calibrating
and/or standardizing operations. These records, containing the date of the operation, shall
describe whether the maintenance operations were routine and followed the written standard
operating procedures. Written records shall be kept of nonroutine repairs performed on
equipment as a result of failure and malfunction. Such records shall document the nature of
the defect, how and when the defect was discovered, and any remedial action taken in
response to the defect.
1 0 . Testing Facilities Operation
Sample tracking vary among laboratories. Receipt, handling, sampling and storage should
be prepared appropriately. Records including test item and reference item characterisation,
date of receipt, expiry date, quantities received and used in studies should be maintained.
Handling, sampling, and storage procedures should be identified in order that the
homogeneity and stability are assured to the degree possible and contamination or mixup are
precluded. They should maintain the unmistakable connection between a set of analytical
data and the samples from which they were obtained. Original source of samples must be
recorded and unmistakably connected with the set of analytical data. Records including test
item and reference item characterization, date of receipt, expiry date, quantities received and
used in studies should be maintained. Handling, sampling, and storage procedures should
be identified in order that the homogeneity and stability are assured to the degree

possible and contamination or mix-up are precluded. Storage container(s) should carry
identification information, expiry date, and specific storage instructions. Receipt and storage
areas for specimens must be separate from storage areas for pesticide formulations and other
test or reference items. Areas used for specimen and sample preparation, instrumentation,
calibration of sprays, reference Standard preparation, and for washing glassware should be
adequately isolated from each other and from other functions of the laboratory which might
introduce contamination. Storage areas for test and reference items at all test sites
should be environmentally monitored, if required, to assure conformance with
established stability limits for these materials. Test and reference items should not be placed
in the same storage containers with collected test system specimens and other materials of
low concentrations which are being stored for shipment to the analytical laboratory or to
off-site archives. There should be adequate storage and disposal facilities available for
pesticide and related wastes such that there is no potential for crosscontamination
of test systems, of test or reference items or of collected specimens. (OECD, 1998). Storage
container(s) should carry identification information, expiry date, and specific storage
instructions Each test and reference item should be properly identified. For each study, the
identity, including batch number, purity, composition, concentrations, or other
characteristics to appropriately define each batch of the test or reference items should be
known. In cases where the test item is supplied by the sponsor, there should be a mechanism,
developed in co-operation between the sponsor and the test facility, to verify the identity of
the test item subject to the study. The stability of test and reference items under storage and
test conditions should be known for all studies. If the test item is administered or applied in a
vehicle, the homogeneity, concentration and stability of the test item in that vehicle should
be determined. A sample for analytical purposes from each batch of test item should be
retained for all studies except short-term studies. A well thought-out concept of logistics is
needed for receiving, storing, handling and disposing test items, together with provisions
for the adequate documentation of all procedures connected with test item handling. One
aspect in this area of test item logistics is the physical location of these activities, and
the GLP Principles underline the importance of identifying adequate facilities for them.
Laboratory records of receipt, handling and storing should be carefully maintained. While
receipt and storage involves mainly the handling of closed containers, the opening of such a
container exposes the test item to the facility environment and leads consequently to the
possibility of contamination of either the test item or the environment. Moreover, the greater
the number of different test items to be performed, the greater the danger that somebody

would. Therefore, work in the special area where test items are prepared for application
has to be carefully organised. For weighing of the test item and its mixing with the
vehicle, it should be made compulsory that only one test item would be present in that
area at any one time. Special attention has to be given to such areas where test, control and
reference items are prepared for in vitro studies. In such studies, the term ―contamination‖
does not only mean ―contamination by traces of other items‖ but also contamination by
microorganisms, etc., hence necessitating areas where the preparation of these items for the
application in the study could be performed under aseptic conditions. By the same reason,
GLP mandates that the available test item storage locations should be separate from the
rooms or areas containing test systems in order to prevent excessive exposure of the systems
to test items other than the intended one.
12. Standard Operating Procedures (SOP)
According to EPA (Environmental Protection Agency) GLP regulations, ―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. Logbooks for recording
temperatures or equipment use, repair, and maintenance, field or laboratory notebooks, forms
for field or laboratory observations, training reports, computer printouts, recorded data from
automated instrument are examples of raw data. It’s so hard and not necessary for anyone
remember all these details and that’s one of the functions of the Standard Operating
Procedures (SOPs). In FDA it is said that ―If it is not documented..., it did not happen!‖ or,
it’s a rumor!‖ GLPs SOPs Can’t do Guarantee ―good science‖, guarantee good
documentation, replace common sense, prevent all mistakes. SOPs are written procedures
for a laboratories program. They are approved protocols indicating test objectives and
methods. Standard Operating Procedures are intended to ensure the quality and
integrity of the data generated by the test facility. Revisions to Standard Operating
Procedures should be approved by test facility management (OECD, 1998). They define
how to carry out protocol-specified activities. SOPs are most often written in a
chronological listing of action steps. They are written to explain how the procedures are
supposed to work SOP of routine inspection, cleaning, maintenance, testing and calibration,
actions to be taken in response to equipment failure, analytical methods, definition of raw
data, keeping records, reporting, storage, mixing, and recovery of data. (Standard Operating
Procedures should have been written and approved by test facility management that are

intended to ensure the quality and integrity of the data generated by that test facility.
Revisions to Standard Operating Procedures should be approved by test facility management.
Each separate test facility unit or area should have at once available current Standard
Operating Procedures relevant to the activities being performed therein. Published text
books, analytical methods, articles and manuals may be used as supplements to these
Standard Operating Procedures. Deviations from Standard Operating Procedures related to
the study should be documented and should be acknowledged by the Study Director and the
Principal Investigator(s). SOPs are written, approved procedures that describe routine
activities that are specific for daily operations at each facility. SOPs should allow
appropriately qualified personnel to perform a procedure once trained. The details given
under each heading are to be considered as illustrative examples. Room preparation and
environmental room conditions for the test system, procedures for receipt, transfer, proper
placement, characterisation, identification and care of the test system, test system
preparation, observations and examinations, before, during and at the conclusion of the study,
handling of test system individuals found in a severe position or dead during the study,
collection, identification and handling of specimens ,siting and placement of test systems in
test conspiracy should be reviewed. And also operation of Quality Assurance personnel in
planning, scheduling, performing, documenting and reporting inspections should be
examined. Personnel should perform the same tasks using the same procedures. SOPs should
accurately reflect how routine tasks are performed written by each facility based on their
specific field and/or laboratory operations. Laboratory management must be sure that the
SOPs used in the laboratory are useful in daily operations. They should be scientifically
sound. And they should always be updated as necessary, rewrites should be the part of the
routine process. While writing SOP guidelines there must be some precautions such as
avoiding restrictive language such as ―vortex for exactly 1 minute‖ but include clear
instructions such as ―vortex until homogenized‖ if that satisfies the purpose. Unnecessary
steps should not be added such as ―consult the manual‖ unless personnel are required to
follow this step. Study personnel should easily access to the study plan and appropriate
Standard Operating Procedures should be applicable to their involvement in the study. It is
their responsibility to comply with the instructions given in these documents. Study
personnel should exercise health precautions to minimise risk to themselves and to ensure the
integrity of the study.

13. Apparatus, Reagents and Solutions
a. Apparatus: Apparatus used for the generation of data, and for controlling environmental
factors relevant to the study should be suitably located and of appropriate design and
adequate capacity. Apparatus used in a study should be periodically inspected, cleaned,
maintained, and calibrated according to Standard Operating Procedures. Records of
procedures should be maintained.
b. Reagents: Reagents should be labelled, as appropriate, to indicate source, identity,
concentration, and stability information and should include the preparation date, earliest
expiration date, specific storage instructions.
c. Test systems: Apparatus used for the generation of physical/chemical data should be
suitably located appropriate design and adequate capacity. Reference substances should be
used to assist in ensuring the integrity of the physical/chemical test systems in case of
biological samples. Proper conditions should be established and maintained for the housing,
handling and care of animals, plants, microbial as well as other cellular and
sub-cellular systems, in order to ensure the quality of the data. In addition, conditions
should comply with appropriate regulatory requirements for the import, collection, care and
use of animals, plants, microbial as well as other cellular and sub-cellular systems. Newly
received animal and plant test systems should be isolated until their health status has been
evaluated. If any unusual mortality or morbidity occurs, this lot should not be used in
studies and, when appropriate, humanely destroyed. Records of source date of arrival, and
arrival condition should be maintained. Animal, plant, microbial, and cellular test systems
should be acclimatized to the test environment for an adequate period before a study is
initiated. All information needed to properly identify the test systems should appear on their
housing or containers. The diagnosis and treatment of any disease before or during a study
should be recorded.
d. Test and reference substances: Receipt, Handling, Sampling and Storage Records
including substance characterization, date of receipt, quantities received, and used in studies
should be maintained. Handling, sampling, and storage procedures should be identified in
order that the homogeneity and stability is assured to the degree possible and contamination
or mix-up are precluded. Storage container(s) should carry identification information, earliest
expiration date, and specific storage instructions. Characterization Each test and reference
substance should be appropriately identified (e.g. code, Chemical abstract number (CAS),
name), batch number, purity,composition, concentrations, or other characterizationsto
appropriately define each batch of the test or reference substances should be known. Stability

of test and reference under conditions of storage should be known for all studies. If the
test substance is administered in a vehicle, Standard Operating Procedures should be
established for testing the homogeneity and stability of the test substance in that
vehicle sample for analytical purposes from each batch of test substance should be retained
for studies in which the test substance is tested longer than four weeks.
14. Test and control article handling
Procedures shall be established for a system for the handling of the test and control articles
to ensure that:
● There is proper storage.
● Distribution is made in a manner designed to preclude the possibility of contamination,
deterioration, or damage.
● Proper identification is maintained throughout the distribution process.
● The receipt and distribution of each batch is documented. Such documentation shall
include the date and quantity of each batch distributed or returned.
15. Protocol for and Conduct of a Nonclinical Laboratory Study
a. Protocol: (a) Each study shall have an approved written protocol that clearly indicates the
objectives and all methods for the conduct of the study. The protocol shall contain, as
applicable, the following information:
i. A descriptive title and statement of the purpose of the study.
ii. Identification of the test and control articles by name, chemical abstract number, or
code number.
iii. The name of the sponsor and the name and address of the testing facility at which the
study is being conducted.
iv. The number, body weight range, sex, source of supply, species, strain, substrain,
and age of the test system.
v. The procedure for identification of the test system.
vi. A description of the experimental design, including the methods for the control of
bias.
vii. A description and/or identification of the diet used in the study as well as solvents,
emulsifiers, and/or other materials used to solubilize or suspend the test or control articles
before mixing with the carrier. The description shall include specifications for acceptable
levels of contaminants that are reasonably expected to be present in the dietary materials

and are known to be capable of interfering with the purpose or conduct of the study if
present at levels greater than established by the specifications.
viii. Each dosage level, expressed in milligrams per kilogram of body weight or other
appropriate units, of the test or control article to be administered and the method and
frequency of administration.
b. Conduct of a nonclinical laboratory Study: (a) The nonclinical laboratory study shall be
conducted in accordance with the protocol.
i. The test systems shall be monitored in conformity with the protocol.
ii. Specimens shall be identified by test system, study, nature, and date of collection. This
information shall be located on the specimen container or shall accompany the
specimen in a manner that precludes error in the recording and storage of data.
iii. Records of gross findings for a specimen from postmortem observations should be
available to a pathologist when examining that specimen histopathologically.
iv. All data generated during the conduct of a nonclinical laboratory study, except those that
are generated by automated data collection systems, shall be recorded directly,
promptly, and legibly in ink. All data entries shall be dated on the date of entry and signed
or initialed by the person entering the data. Any change in entries shall be made so as not
to obscure the original entry, shall indicate the reason for such change, and shall be dated
and signed or identified at the time of the change. In automated data collection systems, the
individual responsible for direct data input shall be identified at the time of data input.
Any change in automated data entries shall be made so as not to obscure the original entry,
shall indicate the reason for change, shall be dated, and the responsible individual shall be
identified.
16. Records and Reports
The storage of records must enable their safe keeping for long periods of time without loss or
deterioration. In order to encourage safe storage of data, restricted access is used to archive
facilities and record the documents logged in and out to a limited number of staff. During the
conduct of multi-site studies, the temporary storage of materials should be carefully made.
Such storage facilities should be safe enough and protect the integrity of their contents. When
test site storage facilities are not adequate to satisfy GLP requirements, records and materials
should be transferred to a GLP compliant archive. Test site management should ensure that

adequate records are available to demonstrate test site involvement in the study. OECD,
1998).
17. Reporting of nonclinical laboratory study results
(a) A final report shall be prepared for each nonclinical laboratory study and shall include,but
not necessarily be limited to, the following:
i. Name and address of the facility performing the study and the dates on which the study
was initiated and completed.
ii. Objectives and procedures stated in the approved protocol, including any changes in the
original protocol.
iii. Statistical methods employed for analyzing the data.
iv. The test and control articles identified by name, chemical abstracts number or
code number, strength, purity, and composition or other appropriate characteristics.
v. Stability of the test and control articles under the conditions of administration.
vi. A description of the methods used.
vii. A description of the test system used. Where applicable, the final report shall include
the number of animals used, sex, body weight range, source of supply, species, strain and
substrain, age, and procedure used for identification.
viii. A description of the dosage, dosage regimen, route of administration, and duration.
ix. A description of all cirmcumstances that may have affected the quality or integrity of the
data.
x. The name of the study director, the names of other scientists or professionals, and
the names of all supervisory personnel, involved in the study.
xi. A description of the transformations, calculations, or operations performed on the data, a
summary and analysis of the data, and a statement of the conclusions drawn from the
analysis.
xii. The signed and dated reports of each of the individual scientists or other professionals
involved in the study.
xiii. The locations where all specimens, raw data, and the final report are to be stored.
xiv. The statement prepared and signed by the quality assurance unit as described in
58.35(b)(7).
(b). The final report shall be signed and dated by the study director.

(c). Corrections or additions to a final report shall be in the form of an amendment by the
study director. The amendment shall clearly identify that part of the final report that is being
added to or corrected and the reasons for the correction or addition, and shall be signed and
dated by the person responsible.
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against Industrial Bio-Test Laboratories". Amicus Journal (Natural Resources Defence
Council): 14–26.
12. Staff, World Health Organization (2009) Handbook: Good Laboratory Practice (GLP) 13.
"OECD Principles of Good Laboratory Practice (as revised in 1997)". OECD
Environmental Health and Safety Publications (OECD) 1. 1998.
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the quality of experimental toxicological and eco-toxicological data". Regul Toxicol
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When Implementing Automated Methods into GxP Laboratories". Journal of the
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Available:http://www.olis.oecd.org/olis/1998doc.nsf/LinkTo/NT00000C5A/$FILE/01E88
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22. U.S. EPA (U.S. Environmental Protection Agency) Good Laboratory Practice Standards.
2007a. [accessed 2 April 2009]. 40CFR160. Available:http://www. access.gpo.
gov/nara/ cfr/waisidx_07/40cfr160_07.html.
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40CFR792. Available:http://www.access.gpo.gov/nara/cfr/waisidx_07/40cfr792_07.html.
24. Anderson MA. GLP Quality Audit Manual. CRC Press. 2000; 223 - 224.
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