Code of Federal Regulations]

[Title 40, Volume B, Parts 150 to 189]

[Revised as of July 1, 1996]

From the U.S. Government Printing Office via GPO Access

[CITE: 40CFR160]

 

 

 

TITLE 40--PROTECTION OF ENVIRONMENT

 

PART 160--GOOD LABORATORY PRACTICE STANDARDS

 

                      Subpart A--General Provisions

Sec.

160.1  Scope.

160.3  Definitions.

160.10  Applicability to studies performed under grants and contracts.

160.12  Statement of compliance or non-compliance.

160.15  Inspection of a testing facility.

160.17  Effects of non-compliance.

 

                  Subpart B--Organization and Personnel

160.29  Personnel.

160.31  Testing facility management.

160.33  Study director.

160.35  Quality assurance unit.

 

                          Subpart C--Facilities

160.41  General.

160.43  Test system care facilities.

160.45  Test system supply facilities.

160.47  Facilities for handling test, control, and reference substances.

160.49  Laboratory operation areas.

160.51  Specimen and data storage facilities.

 

                          Subpart D--Equipment

160.61  Equipment design.

160.63  Maintenance and calibration of equipment.

 

                 Subpart E--Testing Facilities Operation

160.81  Standard operating procedures.

160.83  Reagents and solutions.

160.90  Animal and other test system care.

 

           Subpart F--Test, Control, and Reference Substances

160.105  Test, control, and reference substance characterization.

160.107  Test, control, and reference substance handling.

160.113  Mixtures of substances with carriers.

 

             Subpart G--Protocol for and Conduct of a Study

160.120  Protocol.

160.130  Conduct of a study.

160.135  Physical and chemical characterization studies.

 

                        Subparts H--I  [Reserved]

 

                    Subpart J--Records and Reports

160.185  Reporting of study results.

160.190  Storage and retrieval of records and data.

160.195  Retention of records.

 

    Authority: 7 U.S.C. 136a, 136c, 136d, 136f, 136j, 136t, 136v, 136w;
21 U.S.C. 346a, 348, 371, Reorganization Plan No. 3 of 1970.

 

    Source: 54 FR 34067, Aug. 17, 1989, unless otherwise noted.

 

                      Subpart A--General Provisions

 

Sec. 160.1   Scope.

 

    (a) This part prescribes good laboratory practices for conducting
studies that support or are intended to support applications for
research or marketing permits for pesticide products regulated by the

EPA. This part is intended to assure the quality and integrity of data
submitted pursuant to sections 3, 4, 5, 8, 18 and 24(c) of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended (7
U.S.C. 136a, 136c, 136f, 136q and 136v(c)) and sections 408 and 409 of
the Federal Food, Drug and Cosmetic Act (FFDCA) (21 U.S.C. 346a, 348).

    (b) This part applies to any study described by paragraph (a) of
this section which any person conducts, initiates, or supports on or
after October 16, 1989.

 

Sec. 160.3   Definitions.

 

    As used in this part the following terms shall have the meanings
specified:

    Application for research or marketing permit includes:

    (1) An application for registration, amended registration, or
reregistration of a pesticide product under FIFRA sections 3, 4 or

24(c).

    (2) An application for an experimental use permit under FIFRA
section 5.

    (3) An application for an exemption under FIFRA section 18.

    (4) A petition or other request for establishment or modification of
a tolerance, for an exemption for the need for a tolerance, or for other
clearance under FFDCA section 408.

    (5) A petition or other request for establishment or modification of
a food additive regulation or other clearance by EPA under FFDCA section
409.

    (6) A submission of data in response to a notice issued by EPA under
FIFRA section 3(c)(2)(B).

    (7) Any other application, petition, or submission sent to EPA
intended to persuade EPA to grant, modify, or leave unmodified a
registration or other approval required as a condition of sale or
distribution of a pesticide.

    Batch means a specific quantity or lot of a test, control, or
reference substance that has been characterized according to

Sec. 160.105(a).

    Carrier means any material, including but not limited to feed,
water, soil, 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 known

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.

    FFDCA means the Federal Food, Drug and Cosmetic Act, as amended (21

U.S.C. 321 et seq).

    FIFRA means the Federal Insecticide, Fungicide and Rodenticide Act

as amended (7 U.S.C. 136 et seq).

    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.

    Specimens 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 support of an
application for a research or marketing permit; 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, product performance (efficacy studies only as required by 40
CFR 158.640), environmental and chemical fate, persistence and residue,

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:

    (1) Is the subject of an application for a research or marketing
permit supported by the study, or is the contemplated subject of such an

application; or

    (2) Is an ingredient, impurity, degradation product, metabolite, or
radioactive isotope of a substance described by paragraph (1) of this
definition, or some other substance related to a substance described by
that paragraph, which is used in the study to assist in characterizing
the toxicity, metabolism, or other characteristics of a substance
described by that paragraph.

    Test system means any animal, plant, microorganism, chemical or
physical matrix, including but not limited to soil or water, or subparts
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.

    Vehicle means any agent which facilitates the mixture, dispersion,

or solubilization of a test substance with a carrier.

 

Sec. 160.10  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.

 

Sec. 160.12  Statement of compliance or non-compliance.

 

    Any person who submits to EPA an application for a research or
marketing permit and who, in connection with the application, submits
data from a study to which this part applies shall include in the
application a true and correct statement, signed by the applicant, the
sponsor, and the study director, of one of the following types:    

 (a) A statement that the study was conducted in accordance with this
part; or

    (b) A statement describing in detail all differences between the
practices used in the study and those required by this part; or

    (c) A statement that the person was not a sponsor of the study, did
not conduct the study, and does not know whether the study was conducted
in accordance with this part.

 

Sec. 160.15  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 should not apply to quality
assurance unit records of findings and problems, or to actions
recommended and taken, except that EPA may seek production of these
records in litigation or formal adjudicatory hearings.

    (b) EPA will not consider reliable for purposes of supporting an
application for a research or marketing permit 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 in support of an application for a research or marketing
permit does not, however, relieve the applicant for such a permit of any
obligation under any applicable statute or regulation to submit the
results of the study to EPA.

 

Sec. 160.17  Effects of non-compliance.

 

    (a) EPA may refuse to consider reliable for purposes of supporting
an application for a research or marketing permit any data from a study
which was not conducted in accordance with this part.

    (b) Submission of a statement required by Sec. 160.12 which is false
may form the basis for cancellation, suspension, or modification of the

research or marketing permit, or denial or disapproval of an application
for such a permit, under FIFRA section 3, 5, 6, 18, or 24 or FFDCA
section 406 or 409, or for criminal prosecution under 18 U.S.C. 2 or
1001 or FIFRA section 14, or for imposition of civil penalties under
FIFRA section 14.

 

                  Subpart B--Organization and Personnel

 

Sec. 160.29  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, and test, control, and
reference substances, and any other operation or function that may
adversely affect the study until the condition is corrected. All
personnel shall be instructed to report to their immediate supervisors
any health or medical conditions that may reasonably be considered to
have an adverse effect on a study.

 

Sec. 160.31  Testing facility management.

 

    For each study, testing facility management shall:

    (a) Designate a study director as described in Sec. 160.33 before
the study is initiated.

    (b) Replace the study director promptly if it becomes necessary to
do so during the conduct of a study.

    (c) Assure that there is a quality assurance unit as described in

Sec. 160.35.

    (d) Assure that test, control, and reference substances or mixtures

have been appropriately tested for identity, strength, purity,
stability, and uniformity, as applicable.

    (e) Assure that personnel, resources, facilities, equipment,
materials and methodologies are available as scheduled.

    (f) Assure that personnel clearly understand the functions they are
to perform.

    (g) Assure that any deviations from these regulations reported by
the quality assurance unit are communicated to the study director and
corrective actions are taken and documented.

 

Sec. 160.33  Study director.

 

    For each study, a scientist or other professional of appropriate
education, training, and experience, or combination thereof, shall be
identified as the study director. The study director has overall
responsibility for the technical conduct of the study, as well as for
the interpretation, analysis, documentation, and reporting of results,
and represents the single point of study control. The study director

shall assure that:

    (a) The protocol, including any change, is approved as provided by

Sec. 160.120 and is followed.

    (b) All experimental data, including observations of unanticipated
responses of the test system are accurately recorded and verified.

    (c) Unforseen circumstances that may affect the quality and
integrity of the study are noted when they occur, and corrective action
is taken and documented.

    (d) Test systems are as specified in the protocol.

    (e) All applicable good laboratory practice regulations are
followed.

    (f) All raw data, documentation, protocols, specimens, and final
reports are transferred to the archives during or at the close of the

study.

 

Sec. 160.35  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
reinspection. Any problems which are likely to affect study integrity
found during the course of an inspection shall be brought to the
attention of the study director and management immediately.

    (4) Periodically submit to management and the study director written
status reports on each study, noting any problems and the corrective
actions taken.

    (5) Determine that no deviations from approved protocols or standard

operating procedures were made without proper authorization and
documentation.

    (6) Review the final study report to assure that such report
accurately describes the methods and standard operating procedures, and
that the reported results accurately reflect the raw data of the study.

    (7) Prepare and sign a statement to be included with the final study
report which shall specify the dates inspections were made and findings
reported to management and to the study director.

    (c) The responsibilities and procedures applicable to the quality
assurance unit, the records maintained by the quality assurance unit,
and the method of indexing such records shall be in writing and shall be
maintained. These items including inspection dates, the study inspected,
the phase or segment of the study inspected, and the name of the
individual performing the inspection shall be made available for
inspection to authorized employees or duly designated representatives of

EPA or FDA.

    (d) An authorized employee or a duly designated representative of
EPA or FDA shall have access to the written procedures established for
the inspection and may request testing facility management to certify
that inspections are being implemented, performed, documented, and
followed up in accordance with this paragraph.

 

                          Subpart C--Facilities

 

Sec. 160.41  General.

 

    Each testing facility shall be of suitable size and construction to
facilitate the proper conduct of studies. Testing facilities which are

not located within an indoor controlled environment shall be of suitable
location to facilitate the proper conduct of studies. Testing facilities

shall be designed so that there is a degree of separation that will
prevent any function or activity from having an adverse effect on the

study.

 

Sec. 160.43  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 paragraph (a) of this
section to ensure isolation of studies being done with test systems or
test, control, and reference substances known to be biohazardous,
including volatile substances, aerosols, radioactive materials, and
infectious agents.

    (c) Separate areas shall be provided, as appropriate, for the
diagnosis, treatment, and control of laboratory test system diseases.
These areas shall provide effective isolation for the housing of test
systems either known or suspected of being diseased, or of being
carriers of disease, from other test systems.

    (d) Facilities shall have proper provisions for collection and
disposal of contaminated water, soil, or other spent materials. When
animals are housed, facilities shall exist for the collection and

disposal of all animal waste and refuse or for safe sanitary storage of
waste before removal from the testing facility. Disposal facilities
shall be so provided and operated as to minimize vermin infestation,
odors, disease hazards, and environmental contamination.

    (e) Facilities shall have provisions to regulate environmental
conditions (e.g., temperature, humidity, photoperiod) as specified in

the protocol.

    (f) For marine test organisms, an adequate supply of clean sea water
or artificial sea water (prepared from deionized or distilled water and
sea salt mixture) shall be available. The ranges of composition shall be
as specified in the protocol.

    (g) For freshwater organisms, an adequate supply of clean water of
the appropriate hardness, pH, and temperature, and which is free of
contaminants capable of interfering with the study, shall be available
as specified in the protocol.

    (h) For plants, an adequate supply of soil of the appropriate
composition, as specified in the protocol, shall be available as needed.

 

Sec. 160.45  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. As
specified in the protocol, these include:

    (1) Facilities for holding, culturing, and maintaining algae and
aquatic plants.

    (2) Facilities for plant growth, including, but not limited to
greenhouses, growth chambers, light banks, and fields.

    (c) When appropriate, facilities for aquatic animal tests shall be

provided. These include, but are not limited to, aquaria, holding tanks,

ponds, and ancillary equipment, as specified in the protocol.

 

Sec. 160.47  Facilities for handling test, control, and reference 
substances.

 

    (a) As necessary to prevent contamination or mixups, there shall be
separate areas for:

    (1) Receipt and storage of the test, control, and reference
substances.

    (2) Mixing of the test, control, and reference substances with a
carrier, e.g., feed.

    (3) Storage of the test, control, and reference substance mixtures. 
   (b) Storage areas for test, control, and/or reference substance and
for test, control, and/or reference mixtures shall be separate from
areas housing the test systems and shall be adequate to preserve the
identity, strength, purity, and stability of the substances and
mixtures.

 

Sec. 160.49  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.

 

Sec. 160.51  Specimen and data storage facilities.

 

    Space shall be provided for archives, limited to access by
authorized personnel only, for the storage and retrieval of all raw data
and specimens from completed studies.

 

                          Subpart D--Equipment

 

Sec. 160.61   Equipment design.

 

    Equipment used in the generation, measurement, or assessment of data

and equipment used for facility environmental control shall be of
appropriate design and adequate capacity to function according to the
protocol and shall be suitably located for operation, inspection,
cleaning, and maintenance.

 

Sec. 160.63   Maintenance and calibration of equipment.

 

    (a) Equipment shall be adequately inspected, cleaned, and
maintained. Equipment used for the generation, measurement, or
assessment of data shall be adequately tested, calibrated, and/or
standardized.

    (b) The written standard operating procedures required under Sec.
160.81(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 dates of the operations, shall describe
whether the maintenance operations were routine and followed the written
standard operating procedures. Written records shall be kept of
nonroutine repairs performed on equipment as a result of failure and
malfunction. Such records shall document the nature of the defect, how
and when the defect was discovered, and any remedial action taken in
response to the defect.

 

                 Subpart E--Testing Facilities Operation

 

Sec. 160.81   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 area preparation.

    (2) Test system care.

    (3) Receipt, identification, storage, handling, mixing, and method
of sampling of the test, control, and reference substances.

    (4) Test system observations.

    (5) Laboratory or other tests.

    (6) Handling of test systems found moribund or dead during study.

    (7) Necropsy of test systems or postmortem examination of test
systems.

    (8) Collection and identification of specimens.

    (9) Histopathology.

    (10) Data handling, storage and retrieval.

    (11) Maintenance and calibration of equipment.

    (12) Transfer, proper placement, and identification of test systems.

    (c) Each laboratory or other study area shall have immediately

available manuals and standard operating procedures relative to the
laboratory or field procedures being performed. Published literature may
be used as a supplement to standard operating procedures.

    (d) A historical file of standard operating procedures, and all
revisions thereof, including the dates of such revisions, shall be
maintained.

 

Sec. 160.83   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.

 

Sec. 160.90   Animal and other test system care.

 

    (a) There shall be standard operating procedures for the housing,
feeding, handling, and care of animals and other test systems.

    (b) All newly received test systems from outside sources shall be
isolated and their health status or appropriateness for the study shall
be evaluated. This evaluation shall be in accordance with acceptable
veterinary medical practice or scientific methods.

    (c) At the initiation of a study, test systems shall be free of any
disease or condition that might interfere with the purpose or conduct of
the study. If during the course of the study, the test systems contract
such a disease or condition, the diseased test systems should be
isolated, if necessary. These test systems may be treated for disease or
signs of disease provided that such treatment does not interfere with
the study. The diagnosis, authorization of treatment, description of
treatment, and each date of treatment shall be documented and shall be
retained.

    (d) Warm-blooded animals, adult reptiles, and adult terrestrial
amphibians used in laboratory procedures that require manipulations and
observations over an extended period of time or in studies that require
these test systems to be removed from and returned to their test system-
housing units for any reason (e.g., cage cleaning, treatment, etc.),
shall receive appropriate identification (e.g., tattoo, color code, ear
tag, ear punch, etc.). All information needed to specifically identify
each test system within the test system-housing unit shall appear on the
outside of that unit. Suckling mammals and juvenile birds are excluded
from the requirement of individual identification unless otherwise
specified in the protocol.

    (e) Except as specified in paragraph (e)(1) of this section, test

systems of different species shall be housed in separate rooms when
necessary. Test systems of the same species, but used in different
studies, should not ordinarily be housed in the same room when

inadvertent exposure to test, control, or reference substances or test
system mixup could affect the outcome of either study. If such mixed
housing is necessary, adequate differentiation by space and
identification shall be made.

    (1) Plants, invertebrate animals, aquatic vertebrate animals, and
may be used in multispecies tests need not be housed in separate

rooms, provided that they are adequately segregated to avoid mixup and
cross contamination.

    (2) [Reserved]

    (f) Cages, racks, pens, enclosures, aquaria, holding tanks, ponds,
growth chambers, and other holding, rearing and breeding areas, and
accessory equipment, shall be cleaned and sanitized at appropriate
intervals.

    (g) Feed, soil, and water used for the test systems shall be
analyzed periodically to ensure that contaminants known to be capable of
interfering with the study and reasonably expected to be present in such
feed, soil, or water are not present at levels above those specified in
the protocol. Documentation of such analyses shall be maintained as raw
data.

    (h) Bedding used in animal cages or pens shall not interfere with
the purpose or conduct of the study and shall be changed as often as
necessary to keep the animals dry and clean.

    (i) If any pest control materials are used, the use shall be
documented. Cleaning and pest control materials that interfere with the
study shall not be used.

    (j) All plant and animal test systems shall be acclimatized to the
environmental conditions of the test, prior to their use in a study.

 

           Subpart F--Test, Control, and Reference Substances

 

Sec. 160.105  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 shal1 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 the location of
such documentation shall be specified.

    (b) When relevant to the conduct of the study the solubility of each
test, control, or reference substance shall be determined by the testing
facility or the sponsor before the experimental start date. The
stability of the test, control, or reference substance shall be
determined before the experimental start date or concomitantly according

to written standard operating procedures, which provide for periodic
analysis of each batch.

    (c) Each storage container for a test, control, or reference

substance shall be labeled by name, chemical abstracts service number
(CAS) or code number, batch number, expiration date, if any, and, where
appropriate, storage conditions necessary to maintain the identity,
strength, purity, and composition of the test, control, or reference
substance. Storage containers shall be assigned to a particular test
substance for the duration of the study.

    (d) For studies of more than 4 weeks experimental duration, reserve
samples from each batch of test, control, and reference substances shall
be retained for the period of time provided by Sec. 160.195.

    (e) The stability of test, control, and reference substances under
storage conditions at the test site shall be known for all studies.

 

Sec. 160.107  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 

    (d) The receipt and distribution of each batch is documented. Such
documentation shall include the date and quantity of each batch
distributed or returned.

 

Sec. 160.113  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 study, to determine the
solubility of each test, control, or reference substance in the mixture

by the testing facility or the sponsor before the experimental start
date.

    (3) To determine the stability of the test, control, or reference
substance in the mixture before the experimental start date or
concomitantly according to written standard operating procedures, which

provide for periodic analysis of each batch.

    (b) Where any of the components of the test, control, or reference
substance carrier mixture has an expiration date, that date shall be
clearly shown on the container. If more than one component has an
expiration date, the earliest date shall be shown.

    (c) If a vehicle is used to facilitate the mixing of a test

substance with a carrier, assurance shall be provided that the vehicle

does not interfere with the integrity of the test.

 

             Subpart G--Protocol for and Conduct of a Study

 

Sec. 160.120  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 range, 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 to be used.    
(b) All changes in or revisions of an approved protocol and the reasons
therefore shall be documented, signed by the study director, dated, and
maintained with the protocol.

 

Sec. 160.130  Conduct of a study.

 

    (a) The study shall be conducted in accordance with the protocol.

    (b) The test systems shall be monitored in conformity with the
protocol.

    (c) Specimens shall be identified by test system, study, nature, and
date of collection. This information shall be located on the specimen
container or shall accompany the specimen in a manner that precludes
error in the recording and storage of data.

    (d) In animal studies where histopathology is required, records of
gross findings for a specimen from postmortem observations shall be

available to a pathologist when examining that specimen
histopathologically.

    (e) All data generated during the conduct of a study, except those
that are generated by automated data collection systems, shall be
recorded directly, promptly, and legibly in ink. All data entries shall
be dated on the day of entry and signed or initialed by the person
entering the data. Any change in entries shall be made so as not to

obscure the original entry, shall indicate the reason for such change,
and shall be dated and signed or identified at the time of the change.
In automated data collection systems, the individual responsible for
direct data input shall be identified at the time of data input. Any
change in automated data entries shall be made so as not to obscure the
original entry, shall indicate the reason for change, shall be dated,
and the responsible individual shall be identified.

 

Sec. 160.135  Physical and chemical characterization studies.

 

    (a) All provisions of the GLP standards 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) of test, control, or reference substances.

    (b) The following GLP standards shall not apply to studies, other
than those designated in paragraph (a) of this section, designed to
determine physical and chemical characteristics of a test, control, or

reference substance:

 

Sec. 160.31 (c), (d), and (g)

Sec. 160.35 (b) and (c)

Sec. 160.43

Sec. 160.45

Sec. 160.47

Sec. 160.49

Sec. 160.81(b) (1), (2), (6) through (9), and (12)

Sec. 160.90

Sec. 160.105 (a) through (d)

Sec. 160.113

Sec. 160.120(a) (5) through (12), and (15)

Sec. 160.185(a) (5) through (8), (10), (12), and (14)

Sec. 160.195 (c) and (d)

 

                        Subparts H--I  [Reserved]

 

                     Subpart J--Records and Reports

 

Sec. 160.185  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 used, sex, body weight
range, source of supply, species, strain and substrain, age, and
procedure used for identification.

    (8) A description of the dosage, dosage regimen, route of
administration, and duration.

    (9) A description of all circumstances that may have affected the
quality or integrity of the data.

    (10) The name of the study director, the names of other scientists
or professionals and the names of all supervisory personnel, involved in
the study.

    (11) A description of the transformations, calculations, or
operations performed on the data, a summary and analysis of the data,
and a statement of the conclusions drawn from the analysis.

    (12) The signed and dated reports of each of the individual
scientists or other professionals involved in the study, including each
person who, at the request or direction of the testing

facility or sponsor, conducted an analysis or evaluation of data or
specimens from the study after data generation was completed.

    (13) The locations where all specimens, raw data, and the final
report are to be stored.

    (14) The statement prepared and signed by the quality assurance unit
as described in Sec. 160.35(b)(7).

    (b) The final report shall be signed and dated by the study
director.

    (c) Corrections or additions to a final report shall be in the form
of an amendment by the study director. The amendment shall clearly
identify that part of the final report that is being added to or
corrected and the reasons for the correction or addition, and shall be
signed and dated by the person responsible. Modification of a final
report to comply with the submission requirements of EPA does not
constitute a correction, addition, or amendment to a final report.

    (d) A copy of the final report and of any amendment to it shall be
maintained by the sponsor and the test facility.

 

Sec. 160.190  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.

 

Sec. 160.195  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 whichever of the following periods is longest:

    (1) In the case of any study used to support an application for a
research or marketing permit approved by EPA, the period during which
the sponsor holds any research or marketing permit to which the study is
pertinent.

    (2) A period of at least 5 years following the date on which the
results of the study are submitted to the EPA in support of an
application for a research or marketing permit.

    (3) In other situations (e.g., where the study does not result in
the submission of the study in support of an application for a research
or marketing permit), a period of at least 2 years following the date on
which the study is completed, terminated, or discontinued.

    (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, and
biological fluids, do not need to be retained after quality assurance
verification. In no case shall retention be required for longer periods
than those set forth in paragraph (b) of this section.

    (d) The master schedule sheet, copies of protocols, and records of
quality assurance inspections, as required by Sec. 160.35(c) shall be
maintained by the quality assurance unit as an easily accessible system
of records for the period of time specified in paragraph (b) of this
section.

    (e) Summaries of training and experience and job descriptions
required to be maintained by Sec. 160.29(b) may be retained along with
all other testing facility employment records for the length of time
specified in paragraph (b) of this section.

    (f) Records and reports of the maintenance and calibration and
inspection of equipment, as required by Sec. 160.63 (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

