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.
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.ll3 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-1-[Reserved]
Subpart J-Records and Reports
792.185 Reporting of study results.
792.190 Storage and retrieval of and data.
792.195 Retention of records.
(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.
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
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 biological 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 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.
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.
792.12 Statement of compliance or noncompliance.
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.
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.
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 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 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.
Subpart B - Organization and Personnel
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.
792.31 Testing facility management.
For each study, testing facility management shall:
(a) Designate a study director as described in 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 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.
729.33 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 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.
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 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
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.
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 same
chamber, aquarium, or housing unit.
(2) Aquatictoxicity 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.
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.
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.
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.
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
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.
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 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
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.
792.83 Reagents and solutions.
All reagents and solutions in the laboratory areas shall be
labeled to indicate identity, titer or concentration, storage
requirements, and expiration date. Deteriorated or outdated
reagents and solutions shall not be used.
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 Environmental Protection Agency 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.). AH 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
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, 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 792.195.
(e) The stability of test, control, and reference
substances under storage conditions at the test site shall be
known for all studies.
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.
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
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.
(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.
(g) 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) A changes in or revisions of an approved protocol and
the reasons there for shall be documented, signed by the study
director, dated, and maintained with the protocol.
792.130 Conduct of a study.
(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. An 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.
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)
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
792.185 Reporting of study results.
(a) A final report shall be prepared conduct of a study,
except those that 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 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.
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 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.
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) 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. Secimens obtained from
mutagenicity tests, specimens (if 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
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 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 792.63 (b) and
(c), shall be retained for the length of nine 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 faculty 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.
