[Title 40 CFR 792]
[Code of Federal Regulations (annual edition) - July 1, 2002 Edition]
[Title 40 - PROTECTION OF ENVIRONMENT]
[Chapter I - ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)]
[Subchapter R - TOXIC SUBSTANCES CONTROL ACT (CONTINUED)]
[Part 792 - GOOD LABORATORY PRACTICE STANDARDS]
[From the U.S. Government Printing Office]
40PROTECTION OF ENVIRONMENT282002-07-012002-07-01falseGOOD LABORATORY PRACTICE STANDARDS792PART 792PROTECTION OF ENVIRONMENTENVIRONMENTAL PROTECTION AGENCY (CONTINUED)TOXIC SUBSTANCES CONTROL ACT (CONTINUED)
PART 792--GOOD LABORATORY PRACTICE STANDARDS--Table of Contents
Subpart A--General Provisions
Sec.
792.1 Scope.
792.3 Definitions.
792.10 Applicability to studies performed under grants and contracts.
792.12 Statement of compliance or non-compliance.
792.15 Inspection of a testing facility.
792.17 Effects of non-compliance.
Subpart B--Organization and Personnel
792.29 Personnel.
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792.31 Testing facility management.
792.33 Study director.
792.35 Quality assurance unit.
Subpart C--Facilities
792.41 General.
792.43 Test system care facilities.
792.45 Test system supply facilities.
792.47 Facilities for handling test, control, and reference substances.
792.49 Laboratory operation areas.
792.51 Specimen and data storage facilities.
Subpart D--Equipment
792.61 Equipment design.
792.63 Maintenance and calibration of equipment.
Subpart E--Testing Facilities Operation
792.81 Standard operating procedures.
792.83 Reagents and solutions.
792.90 Animal and other test system care.
Subpart F--Test, Control, and Reference Substances
792.105 Test, control, and reference substance characterization.
792.107 Test, control, and reference substance handling.
792.113 Mixtures of substances with carriers.
Subpart G--Protocol for and Conduct of A Study
792.120 Protocol.
792.130 Conduct of a study.
792.135 Physical and chemical characterization studies.
Subparts H-I [Reserved]
Subpart J--Records and Reports
792.185 Reporting of study results.
792.190 Storage and retrieval of records and data.
792.195 Retention of records.
Authority: 15 U.S.C. 2603.
Source: 54 FR 34043, Aug. 17, 1989, unless otherwise noted.
Subpart A--General Provisions
Sec. 792.1 Scope.
(a) This part prescribes good laboratory practices for conducting
studies relating to health effects, environmental effects, and chemical
fate testing. This part is intended to ensure the quality and integrity
of data submitted pursuant to testing consent agreements and test rules
issued under section 4 of the Toxic Substances Control Act (TSCA) (Pub.
L. 94-469, 90 Stat. 2006, 15 U.S.C. 2603 et seq.).
(b) This part applies to any study described by paragraph (a) of
this section which any person conducts, initiates, or supports on or
after September 18, 1989.
(c) It is EPA's policy that all data developed under section 5 of
TSCA be in accordance with provisions of this part. If data are not
developed in accordance with the provisions of this part, EPA will
consider such data insufficient to evaluate the health and environmental
effects of the chemical substances unless the submitter provides
additional information demonstrating that the data are reliable and
adequate.
Sec. 792.3 Definitions.
As used in this part the following terms shall have the meanings
specified:
Batch means a specific quantity or lot of a test, control, or
reference substance that has been characterized according to
Sec. 792.105(a).
Carrier means any material, including but not limited to, feed,
water, soil, and nutrient media, with which the test substance is
combined for administration to a test system.
Control substance means any chemical substance or mixture, or any
other material other than a test substance, feed, or water, that is
administered to the test system in the course of a study for the purpose
of establishing a basis for comparison with the test substance for
chemical or biologicaI measurements.
EPA means the U.S. Environmental Protection Agency.
Experimental start date means the first date the test substance is
applied to the test system.
Experimental termination date means the last date on which data are
collected directly from the study.
FDA means the U.S. Food and Drug Administration.
Person includes an individual, partnership, corporation,
association, scientific or academic establishment, government agency, or
organizational unit thereof, and any other legal entity.
Quality assurance unit means any person or organizational element,
except
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the study director, designated by testing facility management to perform
the duties relating to quality assurance of the studies.
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. In the event that exact
transcripts of raw data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by signature), the
exact copy or exact transcript may be substituted for the original
source as raw data. ``Raw data'' may include photographs, microfilm or
microfiche copies, computer printouts, magnetic media, including
dictated observations, and recorded data from automated instruments.
Reference substance means any chemical substance or mixture, or
analytical standard, or material other than a test substance, feed, or
water, that is administered to or used in analyzing the test system in
the course of a study for the purposes of establishing a basis for
comparison with the test substance for known chemical or biological
measurements.
Specimen means any material derived from a test system for
examination or analysis.
Sponsor means:
(1) A person who initiates and supports, by provision of financial
or other resources, a study;
(2) A person who submits a study to the EPA in response to a TSCA
section 4(a) test rule and/or a person who submits a study under a TSCA
section 4 testing consent agreement or a TSCA section 5 rule or order to
the extent the agreement, rule or order references this part; or
(3) A testing facility, if it both initiates and actually conducts
the study.
Study means any experiment at one or more test sites, in which a
test substance is studied in a test system under laboratory conditions
or in the environment to determine or help predict its effects,
metabolism, environmental and chemical fate, persistence, or other
characteristics in humans, other living organisms, or media. The term
``study'' does not include basic exploratory studies carried out to
determine whether a test substance or a test method has any potential
utility.
Study completion date means the date the final report is signed by
the study director.
Study director means the individual responsible for the overall
conduct of a study.
Study initiation date means the date the protocol is signed by the
study director.
Test substance means a substance or mixture administered or added to
a test system in a study, which substance or mixture is used to develop
data to meet the requirements of a TSCA section 4(a) test rule and/or is
developed under a TSCA section 4 testing consent agreement or section 5
rule or order to the extent the agreement, rule or order references this
part.
Test system means any animal, plant, microorganism, chemical or
physical matrix, including but not limited to, soil or water, or
components thereof, to which the test, control, or reference substance
is administered or added for study. ``Test system'' also includes
appropriate groups or components of the system not treated with the
test, control, or reference substance.
Testing facility means a person who actually conducts a study, i.e.,
actually uses the test substance in a test system. ``Testing facility''
encompasses only those operational units that are being or have been
used to conduct studies.
TSCA means the Toxic Substances Control Act (15 U.S.C, 2601 et seq.)
Vehicle means any agent which facilitates the mixture, dispersion,
or solubilization of a test substance with a carrier.
Sec. 792.10 Applicability to studies performed under grants and contracts.
When a sponsor or other person utilizes the services of a consulting
laboratory, contractor, or grantee to perform all or a part of a study
to which this part applies, it shall notify the consulting laboratory,
contractor, or grantee that the service is, or is part of, a study that
must be conducted in compliance with the provisions of this part.
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Sec. 792.12 Statement of compliance or non-compliance.
Any person who submits to EPA a test required by a testing consent
agreement or a test rule issued under section 4 of TSCA shall include in
the submission a true and correct statement, signed by the sponsor and
the study director, of one of the following types:
(a) A statement that the study was conducted in accordance with this
part; or
(b) A statement describing in detail all differences between the
practices used in the study and those required by this part; or
(c) A statement that the person was not a sponsor of the study, did
not conduct the study, and does not know whether the study was conducted
in accordance with this part.
Sec. 792.15 Inspection of a testing facility.
(a) A testing facility shall permit an authorized employee or duly
designated representative of EPA or FDA, at reasonable times and in a
reasonable manner, to inspect the facility and to inspect (and in the
case of records also to copy) all records and specimens required to be
maintained regarding studies to which this part applies. The records
inspection and copying requirements shall not apply to quality assurance
unit records of findings and problems, or to actions recommended and
taken, except the EPA may seek production of these records in litigation
or formal adjudicatory hearings.
(b) EPA will not consider reliable for purposes of showing that a
chemical substance or mixture does not present a risk of injury to
health or the environment any data developed by a testing facility or
sponsor that refuses to permit inspection in accordance with this part.
The determination that a study will not be considered reliable does not,
however, relieve the sponsor of a required test of any obligation under
any applicable statute or regulation to submit the results of the study
to EPA.
(c) Since a testing facility is a place where chemicals are stored
or held, it is subject to inspection under section 11 of TSCA.
Sec. 792.17 Effects of non-compliance.
(a) The sponsor or any other person who is conducting or has
conducted a test to fulfill the requirements of a testing consent
agreement or a test rule issued under section 4 of TSCA will be in
violation of section 15 of TSCA if:
(1) The test is not being or was not conducted in accordance with
any requirement of this part;
(2) Data or information submitted to EPA under this part (including
the statement required by Sec. 792.12) include information or data that
are false or misleading, contain significant omissions, or otherwise do
not fulfill the requirements of this part; or
(3) Entry in accordance with Sec. 792.15 for the purpose of auditing
test data or inspecting test facilities is denied. Persons who violate
the provisions of this part may be subject to civil or criminal
penalties under section 16 of TSCA, legal action in United States
district court under section 17 of TSCA, or criminal prosecution under
18 U.S.C. 2 or 1001.
(b) EPA, at its discretion, may not consider reliable for purposes
of showing that a chemical substance or mixture does not present a risk
of injury to health or the environment any study which was not conducted
in accordance with this part. EPA, at its discretion, may rely upon such
studies for purposes of showing adverse effects. The determination that
a study will not be considered reliable does not, however, relieve the
sponsor of a required test of the obligation under any applicable
statute or regulation to submit the results of the study to EPA.
(c) If data submitted to fulfill a requirement of a testing consent
agreement or a test rule issued under section 4 of TSCA are not
developed in accordance with this part, EPA may determine that the
sponsor has not fulfilled its obligations under section 4 of TSCA and
may require the sponsor to develop data in accordance with the
requirements of this part in order to satisfy such obligations.
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Subpart B--Organization and Personnel
Sec. 792.29 Personnel.
(a) Each individual engaged in the conduct of or responsible for the
supervision of a 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 study.
(c) There shall be a sufficient number of personnel for the timely
and proper conduct of the study according to the protocol.
(d) Personnel shall take necessary personal sanitation and health
precautions designed to avoid contamination of test, control, and
reference substances and test systems.
(e) Personnel engaged in a study shall wear clothing appropriate for
the duties they perform. Such clothing shall be changed as often as
necessary to prevent microbiological, radiological, or chemical
contamination of test systems and test, control, and reference
substances.
(f) Any individual found at any time to have an illness that may
adversely affect the quality and integrity of the study shall be
excluded from direct contact with test systems, test, control, and
reference substances and any other operation or function that may
adversely affect the study until the condition is corrected. All
personnel shall be instructed to report to their immediate supervisors
any health or medical conditions that may reasonably be considered to
have an adverse effect on a study.
Sec. 792.31 Testing facility management.
For each study, testing facility management shall:
(a) Designate a study director as described in Sec. 792.33 before
the study is initiated.
(b) Replace the study director promptly if it becomes necessary to
do so during the conduct of a study.
(c) Assure that there is a quality assurance unit as described in
Sec. 792.35.
(d) Assure that test, control, and reference substances or mixtures
have been appropriately tested for identity, strength, purity,
stability, and uniformity, as applicable.
(e) Assure that personnel, resources, facilities, equipment,
materials and methodologies are available as scheduled.
(f) Assure that personnel clearly understand the functions they are
to perform.
(g) Assure that any deviations from these regulations reported by
the quality assurance unit are communicated to the study director and
corrective actions are taken and documented.
Sec. 792.33 Study director.
For each 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. The study director
shall assure that:
(a) The protocol, including any change, is approved as provided by
Sec. 792.120 and is followed.
(b) All experimental data, including observations of unanticipated
responses of the test system are accurately recorded and verified.
(c) Unforeseen circumstances that may affect the quality and
integrity of the study are noted when they occur, and corrective action
is taken and documented.
(d) Test systems are as specified in the protocol.
(e) All applicable good laboratory practice regulations are
followed.
(f) All raw data, documentation, protocols, specimens, and final
reports are transferred to the archives during or at the close of the
study.
Sec. 792.35 Quality assurance unit.
(a) 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
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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 conduct inspections and maintain records
appropriate to the study.
(b) The quality assurance unit shall:
(1) Maintain a copy of a master schedule sheet of all studies
conducted at the testing facility indexed by test substance 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.
(2) Maintain copies of all protocols pertaining to all studies for
which the unit is responsible.
(3) Inspect each study at intervals adequate to ensure 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. Any problems which are likely to affect study integrity
found during the course of an inspection shall be brought to the
attention of the study director and management immediately.
(4) Periodically submit to management and the study director written
status reports on each study, noting any problems and the corrective
actions taken.
(5) Determine that no deviations from approved protocols or standard
operating procedures were made without proper authorization and
documentation.
(6) Review the final study report to assure that such report
accurately describes the methods and standard operating procedures, and
that the reported results accurately reflect the raw data of the study.
(7) Prepare and sign a statement to be included with the final study
report which shall specify the dates inspections were made and findings
reported to management and to the study director.
(c) The responsibilities and procedures applicable to the quality
assurance unit, the records maintained by the quality assurance unit,
and the method of indexing such records shall be in writing and shall be
maintained. These items including inspection dates, the study inspected,
the phase or segment of the study inspected, and the name of the
individual performing the inspection shall be made available for
inspection to authorized employees or duly designated representatives of
EPA or FDA.
(d) An authorized employee or a duly designated representative of
EPA or FDA shall have access to the written procedures established for
the inspection and may request testing facility management to certify
that inspections are being implemented, performed, documented, and
followed up in accordance with this paragraph.
Subpart C--Facilities
Sec. 792.41 General.
Each testing facility shall be of suitable size and construction to
facilitate the proper conduct of studies. Testing facilities which are
not located within an indoor controlled environment shall be of suitable
location to facilitate the proper conduct of studies. Testing facilities
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.
Sec. 792.43 Test system care facilities.
(a) A testing facility shall have a sufficient number of animal
rooms or other test system areas, as needed, to ensure: proper
separation of species or test systems, isolation of individual projects,
quarantine or isolation of animals or other test systems, and routine or
specialized housing of animals or other test systems.
(1) In tests with plants or aquatic animals, proper separation of
species can be accomplished within a room or area by housing them
separately in different chambers or aquaria. Separation of species is
unnecessary where the protocol specifies the simultaneous exposure of
two or more species in the
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same chamber, aquarium, or housing unit.
(2) Aquatic toxicity tests for individual projects shall be isolated
to the extent necessary to prevent cross-contamination of different
chemicals used in different tests.
(b) A testing facility shall have a number of animal rooms or other
test system areas separate from those described in paragraph (a) of this
section to ensure isolation of studies being done with test systems or
test, control, and reference substances 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 test system diseases.
These areas shall provide effective isolation for the housing of test
systems either known or suspected of being diseased, or of being
carriers of disease, from other test systems.
(d) Facilities shall have proper provisions for collection and
disposal of contaminated water, soil, or other spent materials. 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,
odors, disease hazards, and environmental contamination.
(e) Facilities shall have provisions to regulate environmental
conditions (e.g., temperature, humidity, photoperiod) as specified in
the protocol.
(f) For marine test organisms, an adequate supply of clean sea water
or artificial sea water (prepared from deionized or distilled water and
sea salt mixture) shall be available. The ranges of composition shall be
as specified in the protocol.
(g) For freshwater organisms, an adequate supply of clean water of
the appropriate hardness, pH, and temperature, and which is free of
contaminants capable of interfering with the study shall be available as
specified in the protocol.
(h) For plants, an adequate supply of soil of the appropriate
composition, as specified in the protocol, shall be available as needed.
Sec. 792.45 Test system supply facilities.
(a) There shall be storage areas, as needed, for feed, nutrients,
soils, bedding, supplies, and equipment. Storage areas for feed,
nutrients, soils, and bedding shall be separated from areas where the
test systems are located and shall be protected against infestation or
contamination. Perishable supplies shall be preserved by appropriate
means.
(b) When appropriate, plant supply facilities shall be provided.
These include:
(1) Facilities, as specified in the protocol, for holding,
culturing, and maintaining algae and aquatic plants.
(2) Facilities, as specified in the protocol, for plant growth,
including but not limited to, greenhouses, growth chambers, light banks,
and fields.
(c) When appropriate, facilities for aquatic animal tests shall be
provided. These include but are not limited to aquaria, holding tanks,
ponds, and ancillary equipment, as specified in the protocol.
Sec. 792.47 Facilities for handling test, control, and reference substances.
(a) As necessary to prevent contamination or mixups, there shall be
separate areas for:
(1) Receipt and storage of the test, control, and reference
substances.
(2) Mixing of the test, control, and reference substances with a
carrier, e.g., feed.
(3) Storage of the test, control, and reference substance mixtures.
(b) Storage areas for test, control, and/or reference substance and
for test, control, and/or reference mixtures shall be separate from
areas housing the test systems and shall be adequate to preserve the
identity, strength, purity, and stability of the substances and
mixtures.
Sec. 792.49 Laboratory operation areas.
Separate laboratory space and other space shall be provided, as
needed, for the performance of the routine and specialized procedures
required by studies.
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Sec. 792.51 Specimen and data storage facilities.
Space shall be provided for archives, limited to access by
authorized personnel only, for the storage and retrieval of all raw data
and specimens from completed studies.
Subpart D--Equipment
Sec. 792.61 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.
Sec. 792.63 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
Sec. 792.81(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.
Subpart E--Testing Facilities Operation
Sec. 792.81 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. All deviations in a study from standard operating
procedures shall be authorized by the study director and shall be
documented in the raw data. Significant changes in established standard
operating procedures shall be properly authorized in writing by
management.
(b) Standard operating procedures shall be established for, but not
limited to, the following:
(1) Test system room preparation.
(2) Test system care.
(3) Receipt, identification, storage, handling, mixing, and method
of sampling of the test, control, and reference substances.
(4) Test system observations.
(5) Laboratory or other tests.
(6) Handling of test systems found moribund or dead during study.
(7) Necropsy of test systems or postmortem examination of test
systems.
(8) Collection and identification of specimens.
(9) Histopathology.
(10) Data handling, storage and retrieval.
(11) Maintenance and calibration of equipment.
(12) Transfer, proper placement, and identification of test systems.
(c) Each laboratory or other study area shall have immediately
available manuals and standard operating procedures relative to the
laboratory or field procedures being performed. Published literature may
be used as a supplement to standard operating procedures.
(d) A historical file of standard operating procedures, and all
revisions thereof, including the dates of such revisions, shall be
maintained.
Sec. 792.83 Reagents and solutions.
All reagents and solutions in the laboratory areas shall be labeled
to indicate identity, titer or concentration,
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storage requirements, and expiration date. Deteriorated or outdated
reagents and solutions shall not be used.
Sec. 792.90 Animal and other test system care.
(a) There shall be standard operating procedures for the housing,
feeding, handling, and care of animals and other test systems.
(b) All newly received test systems from outside sources shall be
isolated and their health status or appropriateness for the study shall
be evaluated. This evaluation shall be in accordance with acceptable
veterinary medical practice or scientific methods.
(c) At the initiation of a study, test systems shall be free of any
disease or condition that might interfere with the purpose or conduct of
the study. If during the course of the study, the test systems contract
such a disease or condition, the diseased test systems should be
isolated, if necessary. These test systems may be treated for disease or
signs of disease provided that such treatment does not interfere with
the study. The diagnosis, authorization of treatment, description of
treatment, and each date of treatment shall be documented and shall be
retained.
(d) Warm-blooded animals, adult reptiles, and adult terrestrial
amphibians used in laboratory procedures that require manipulations and
observations over an extended period of time, or in studies that require
these test systems to be removed from and returned to their test system-
housing units for any reason (e.g., cage cleaning, treatment, etc.),
shall receive appropriate identification (e.g., tattoo, color code, ear
tag, ear punch, etc.). All information needed to specifically identify
each test system within the test system-housing unit shall appear on the
outside of that unit. Suckling mammals and juvenile birds are excluded
from the requirement of individual identification unless otherwise
specified in the protocol.
(e) Except as specified in paragraph (e)(1) of this section, test
systems of different species shall be housed in separate rooms when
necessary. Test systems of the same species, but used in different
studies, should not ordinarily be housed in the same room when
inadvertent exposure to test, control, or reference substances or test
system mixup could affect the outcome of either study. If such mixed
housing is necessary, adequate differentiation by space and
identification shall be made.
(1) Plants, invertebrate animals, aquatic vertebrate animals, and
organisms that may be used in multispecies tests need not be housed in
separate rooms, provided that they are adequately segregated to avoid
mixup and cross contamination.
(2) [Reserved]
(f) Cages, racks, pens, enclosures, aquaria, holding tanks, ponds,
growth chambers, and other holding, rearing, and breeding areas, and
accessory equipment, shall be cleaned and sanitized at appropriate
intervals.
(g) Feed, soil, and water used for the test systems shall be
analyzed periodically to ensure that contaminants known to be capable of
interfering with the study and reasonably expected to be present in such
feed, soil, or water are not present at levels above those specified in
the protocol. Documentation of such analyses shall be maintained as raw
data.
(h) Bedding used in animal cages or pens shall not interfere with
the purpose or conduct of the study and shall be changed as often as
necessary to keep the animals dry and clean.
(i) If any pest control materials are used, the use shall be
documented. Cleaning and pest control materials that interfere with the
study shall not be used.
(j) All plant and animal test systems shall be acclimatized to the
environmental conditions of the test, prior to their use in a study.
Subpart F--Test, Control, and Reference Substances
Sec. 792.105 Test, control, and reference substance characterization.
(a) The identity, strength, purity, and composition, or other
characteristics which will appropriately define the test, control, or
reference substance shall be determined for each batch and shall be
documented before its use in a study. Methods of synthesis, fabrication,
or derivation of the test, control,
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or reference substance shall be documented by the sponsor or the testing
facility, and such location of documentation shall be specified.
(b) When relevant to the conduct of the study the solubility of each
test, control, or reference substance shall be determined by the testing
facility or the sponsor before the experimental start date. The
stability of the test, control or reference substance shall be
determined before the experimental start date or concomitantly according
to written standard operating procedures, which provide for periodic
analysis of each batch.
(c) Each storage container for a test, control, or reference
substance shall be labeled by name, chemical abstracts service number
(CAS) or code number, batch number, expiration date, if any, and, where
appropriate, storage conditions necessary to maintain the identity,
strength, purity, and composition of the test, control, or reference
substance. Storage containers shall be assigned to a particular test
substance for the duration of the study.
(d) For studies of more than 4 weeks experimental duration, reserve
samples from each batch of test, control, and reference substances shall
be retained for the period of time provided by Sec. 792.195.
(e) The stability of test, control, and reference substances under
storage conditions at the test site shall be known for all studies.
Sec. 792.107 Test, control, and reference substance handling.
Procedures shall be established for a system for the handling of the
test, control, and reference substances to ensure that:
(a) There is proper storage.
(b) Distribution is made in a manner designed to preclude the
possibility of contamination, deterioration, or damage.
(c) Proper identification is maintained throughout the distribution
process.
(d) The receipt and distribution of each batch is documented. Such
documentation shall include the date and quantity of each batch
distributed or returned.
Sec. 792.113 Mixtures of substances with carriers.
(a) For each test, control, or reference substance that is mixed
with a carrier, tests by appropriate analytical methods shall be
conducted:
(1) To determine the uniformity of the mixture and to determine,
periodically, the concentration of the test, control, or reference
substance in the mixture.
(2) When relevant to the conduct of the experiment, to determine the
solubility of each test, control, or reference substance in the mixture
by the testing facility or the sponsor before the experimental start
date.
(3) To determine the stability of the test, control or reference
substance in the mixture before the experimental start date or
concomitantly according to written standard operating procedures, which
provide for periodic analysis of each batch.
(b) Where any of the components of the test, control, or reference
substance carrier mixture has an expiration date, that date shall be
clearly shown on the container. If more than one component has an
expiration date, the earliest date shall be shown.
(c) If a vehicle is used to facilitate the mixing of a test
substance with a carrier, assurance shall be provided that the vehicle
does not interfere with the integrity of the test.
Subpart G--Protocol for and Conduct of A Study
Sec. 792.120 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 but shall not necessarily be limited to the
following information:
(1) A descriptive title and statement of the purpose of the study.
(2) Identification of the test, control, and reference substance by
name, chemical abstracts service (CAS) number or code number.
(3) The name and address of the sponsor and the name and address of
the testing facility at which the study is being conducted.
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(4) The proposed experimental start and termination dates.
(5) Justification for selection of the test system.
(6) Where applicable, the number, body weight, sex, source of
supply, species, strain, substrain, and age of the test system.
(7) The procedure for identification of the test system.
(8) A description of the experimental design, including methods for
the control of bias.
(9) Where applicable, 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, control, or reference
substances 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.
(10) The route of administration and the reason for its choice.
(11) Each dosage level, expressed in milligrams per kilogram of body
or test system weight or other appropriate units, of the test, control,
or reference substance to be administered and the method and frequency
of administration.
(12) The type and frequency of tests, analyses, and measurements to
be made.
(13) The records to be maintained.
(14) The date of approval of the protocol by the sponsor and the
dated signature of the study director.
(15) A statement of the proposed statistical method.
(b) All changes in or revisions of an approved protocol and the
reasons therefor shall be documented, signed by the study director,
dated, and maintained with the protocol.
Sec. 792.130 Conduct of a study.
(a) The study shall be conducted in accordance with the protocol.
(b) The test systems shall be monitored in conformity with the
protocol.
(c) 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.
(d) In animal studies where histopathology is required, records of
gross findings for a specimen from postmortem observations shall be
available to a pathologist when examining that specimen
histopathologically.
(e) All data generated during the conduct of a 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 day 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.
Sec. 792.135 Physical and chemical characterization studies.
(a) All provisions of the GLPs shall apply to physical and chemical
characterization studies designed to determine stability, solubility,
octanol water partition coefficient, volatility, and persistence (such
as biodegradation, photodegradation, and chemical degradation studies).
(b) The following GLP standards shall not apply to studies designed
to determine physical and chemical characteristics of a test, control,
or reference substance:
Section 792.31 (c), (d), and (g)
Section 792.35 (b) and (c)
Section 792.43
Section 792.45
Section 792.47
Section 792.49
Section 792.81(b) (1), (2), (6) through (9), and (12)
Section 792.90
Section 792.105 (a) through (d)
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Section 792.113
Section 792.120(a) (5) through (12), and (15)
Section 792.185(a) (5) through (8), (10), (12), and (14)
Section 792.195 (c) and (d)
Subparts H-I [Reserved]
Subpart J--Records and Reports
Sec. 792.185 Reporting of study results.
(a) A final report shall be prepared for each study and shall
include, but not necessarily be limited to, the following:
(1) Name and address of the facility performing the study and the
dates on which the study was initiated and was completed, terminated, or
discontinued.
(2) Objectives and procedures stated in the approved protocol,
including any changes in the original protocol.
(3) Statistical methods employed for analyzing the data.
(4) The test, control, and reference substances identified by name,
chemical abstracts service (CAS) number or code number, strength,
purity, and composition, or other appropriate characteristics.
(5) Stability, and when relevant to the conduct of the study, the
solubility of the test, control, and reference substances under the
conditions of administration.
(6) A description of the methods used.
(7) A description of the test system used. Where applicable, the
final report shall include the number of animals or other test organisms
used, sex, body weight range, source of supply, species, strain and
substrain, age, and procedure used for identification.
(8) A description of the dosage, dosage regimen, route of
administration, and duration.
(9) A description of all circumstances that may have affected the
quality or integrity of the data.
(10) The name of the study director, the names of other scientists
or professionals and the names of all supervisory personnel, involved in
the study.
(11) 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.
(12) The signed and dated reports of each of the individual
scientists or other professionals involved in the study, including each
person who, at the request or direction of the testing facility or
sponsor, conducted an analysis or evaluation of data or specimens from
the study after data generation was completed.
(13) The locations where all specimens, raw data, and the final
report are to be stored.
(14) The statement prepared and signed by the quality assurance unit
as described in Sec. 792.35(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. Modification of a final
report to comply with the submission requirements of EPA does not
constitute a correction, addition, or amendment to a final report.
(d) A copy of the final report and of any amendment to it shall be
maintained by the sponsor and the test facility.
Sec. 792.190 Storage and retrieval of records and data.
(a) All raw data, documentation, records, protocols, specimens, and
final reports generated as a result of a study shall be retained.
Specimens obtained from mutagenicity tests, specimens of soil, water,
and plants, and wet specimens of blood, urine, feces, and biological
fluids, do not need to be retained after quality assurance verification.
Correspondence and other documents relating to interpretation and
evaluation of data, other than those documents contained in the final
report, also shall be retained.
(b) There shall be archives for orderly storage and expedient
retrieval of all raw data, documentation, protocols, specimens, and
interim and final reports. Conditions of storage shall minimize
deterioration of the documents or
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specimens in accordance with the requirements for the time period of
their retention and the nature of the documents of specimens. A testing
facility may contract with commercial archives to provide a repository
for all material to be retained. Raw data and specimens may be retained
elsewhere provided that the archives have specific reference to those
other locations.
(c) An individual shall be identified as responsible for the
archives.
(d) Only authorized personnel shall enter the archives.
(e) Material retained or referred to in the archives shall be
indexed to permit expedient retrieval.
Sec. 792.195 Retention of records.
(a) Record retention requirements set forth in this section do not
supersede the record retention requirements of any other regulations in
this subchapter.
(b)(1) Except as provided in paragraph (c) of this section,
documentation records, raw data, and specimens pertaining to a study and
required to be retained by this part shall be retained in the archive(s)
for a period of at least ten years following the effective date of the
applicable final test rule.
(2) In the case of negotiated testing agreements, each agreement
will contain a provision that, except as provided in paragraph (c) of
this section, documentation records, raw data, and specimens pertaining
to a study and required to be retained by this part shall be retained in
the archive(s) for a period of at least ten years following the
publication date of the acceptance of a negotiated test agreement.
(3) In the case of testing submitted under section 5, except for
those items listed in paragraph (c) of this section, documentation
records, raw data, and specimens pertaining to a study and required to
be retained by this part shall be retained in the archive(s) for a
period of at least five years following the date on which the results of
the study are submitted to the agency.
(c) Wet specimens, samples of test, control, or reference
substances, and specially prepared material which are relatively fragile
and differ markedly in stability and quality during storage, shall be
retained only as long as the quality of the preparation affords
evaluation. Specimens obtained from mutagenicity tests, specimens of
soil, water, and plants, and wet specimens of blood, urine, feces,
biological fluids, do not need to be retained after quality assurance
verification. In no case shall retention be required for longer periods
than those set forth in paragraph (b) of this section.
(d) The master schedule sheet, copies of protocols, and records of
quality assurance inspections, as required by Sec. 792.35(c) shall be
maintained by the quality assurance unit as an easily accessible system
of records for the period of time specified in paragraph (b) of this
section.
(e) Summaries of training and experience and job descriptions
required to be maintained by Sec. 792.29(b) may be retained along with
all other testing facility employment records for the length of time
specified in paragraph (b) of this section.
(f) Records and reports of the maintenance and calibration and
inspection of equipment, as required by Sec. 792.63 (b) and (c), shall
be retained for the length of time specified in paragraph (b) of this
section.
(g) If a facility conducting testing or an archive contracting
facility goes out of business, all raw data, documentation, and other
material specified in this section shall be transferred to the archives
of the sponsor of the study. The EPA shall be notified in writing of
such a transfer.
(h) Specimens, samples, or other non-documentary materials need not
be retained after EPA has notified in writing the sponsor or testing
facility holding the materials that retention is no longer required by
EPA. Such notification normally will be furnished upon request after EPA
or FDA has completed an audit of the particular study to which the
materials relate and EPA has concluded that the study was conducted in
accordance with this part.
(i) Records required by this part may be retained either as original
records or as true copies such as photocopies, microfilm, microfiche, or
other accurate reproductions of the original records.
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