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(Last update November 15, 1995)
TOXIC SUBSTANCES CONTROL ACT
40 CFR Part 792-GOOD LABORATORY PRACTICE STANDARDS
Environmental Protection Agency
Thursday, August 17, 1989
- Subpart A-General Provisions
- Section
- 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
-
- 792.31 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.
- 792.49
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
HI-[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.
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Before
initiating a
study
requiring
compliance
with
the
GLPs,
please
contact Dr.
Michael
Mispagel,
UGA's Quality
Assurance Unit,
at
2-5875 to
assist
you
in
meeting
these
standards.
TOXIC SUBSTANCES
CONTROL ACT
40 CFR Part 792-GOOD LABORATORY PRACTICE STANDARDS
Environmental Protection Agency
Thursday, August 17, 1989
Subpart A-General Provisions
- Paragraph 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.
-
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-
- Paragraph 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 Paragraph 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 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.
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-
-
- Section 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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-
-
-
- Section 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.
-
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-
-
- Section 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.
-
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-
- Section 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 Section 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 Section 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
-
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Section 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.
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Section 792.31 Testing facility management.
For each study, testing facility management shall:
(a) Designate a study director as described in Section 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 Section 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.
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Section 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 Section 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.
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Section 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 Section.
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Subpart
C-Facilities
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Section 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.
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Section 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) 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
Section (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.
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Section 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.
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Section 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.
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Section 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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Section 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.
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- Section 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.
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-
- Section 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
Section 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.
-
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Subpart E-Testing Facilities Operation
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- Section 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.
-
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-
- Section 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.
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-
- Section 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 Section (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.
-
-
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Subpart F-Test, Control, and Reference Substances
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Section 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 Section 792.195.
(e) The stability of test, control, and reference substances
under storage conditions at the test site shall be known for
all studies.
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Section 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.
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Section 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.
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Subpart G-Protocol for and Conduct of A Study
Section 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.
- (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.
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Section 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.
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Section 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)
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Subparts HI-[Reserved]
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Subpart J-Records and Reports
Section 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 Section 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.
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Section 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.
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Section 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
Section 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 Section 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 Section 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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