U.S. Food and Drug Administration - Center for Devices and Radiological Health

Code of Federal Regulations
Title 21 - Food and Drugs
Revised as of April 1, 2001

21CFR58.1

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.1]

[Page 303]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                      Subpart A--General Provisions
 
Sec. 58.1  Scope.


    (a) This part prescribes good laboratory practices for conducting 
nonclinical laboratory studies that support or are intended to support 
applications for research or marketing permits for products regulated by 
the Food and Drug Administration, including food and color additives, 
animal food additives, human and animal drugs, medical devices for human 
use, biological products, and electronic products. Compliance with this 
part is intended to assure the quality and integrity of the safety data 
filed pursuant to sections 406, 408, 409, 502, 503, 505, 506, 510, 512-
516, 518-520, 721, and 801 of the Federal Food, Drug, and Cosmetic Act 
and sections 351 and 354-360F of the Public Health Service Act.
    (b) References in this part to regulatory sections of the Code of 
Federal Regulations are to chapter I of title 21, unless otherwise 
noted.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33779, Sept. 4, 1987; 
64 FR 399, Jan. 5, 1999]



21CFR58.3

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.3]

[Page 303-305]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                      Subpart A--General Provisions
 
Sec. 58.3  Definitions.

    As used in this part, the following terms shall have the meanings 
specified:
    (a) Act means the Federal Food, Drug, and Cosmetic Act, as amended 
(secs. 201-902, 52 Stat. 1040 et seq., as amended (21 U.S.C. 321-392)).
    (b) Test article means any food additive, color additive, drug, 
biological product, electronic product, medical device for human use, or 
any other article subject to regulation under the act or under sections 
351 and 354-360F of the Public Health Service Act.
    (c) Control article means any food additive, color additive, drug, 
biological product, electronic product, medical device for human use, or 
any article other than a test article, feed, or water that is 
administered to the test system

[[Page 304]]

in the course of a nonclinical laboratory study for the purpose of 
establishing a basis for comparison with the test article.
    (d) Nonclinical laboratory study means in vivo or in vitro 
experiments in which test articles are studied prospectively in test 
systems under laboratory conditions to determine their safety. The term 
does not include studies utilizing human subjects or clinical studies or 
field trials in animals. The term does not include basic exploratory 
studies carried out to determine whether a test article has any 
potential utility or to determine physical or chemical characteristics 
of a test article.
    (e) Application for research or marketing permit includes:
    (1) A color additive petition, described in part 71.
    (2) A food additive petition, described in parts 171 and 571.
    (3) Data and information regarding a substance submitted as part of 
the procedures for establishing that a substance is generally recognized 
as safe for use, which use results or may reasonably be expected to 
result, directly or indirectly, in its becoming a component or otherwise 
affecting the characteristics of any food, described in Secs. 170.35 and 
570.35.
    (4) Data and information regarding a food additive submitted as part 
of the procedures regarding food additives permitted to be used on an 
interim basis pending additional study, described in Sec. 180.1.
    (5) An investigational new drug application, described in part 312 
of this chapter.
    (6) A new drug application, described in part 314.
    (7) Data and information regarding an over-the-counter drug for 
human use, submitted as part of the procedures for classifying such 
drugs as generally recognized as safe and effective and not misbranded, 
described in part 330.
    (8) Data and information about a substance submitted as part of the 
procedures for establishing a tolerance for unavoidable contaminants in 
food and food-packaging materials, described in parts 109 and 509.
    (9) Data and information regarding an antibiotic drug submitted as 
part of the procedures for issuing, amending, or repealing regulations 
for such drugs, described in Sec. 314.300 of this chapter.
    (10) A Notice of Claimed Investigational Exemption for a New Animal 
Drug, described in part 511.
    (11) A new animal drug application, described in part 514.
    (12) [Reserved]
    (13) An application for a biologics license, described in part 601 
of this chapter.
    (14) An application for an investigational device exemption, 
described in part 812.
    (15) An Application for Premarket Approval of a Medical Device, 
described in section 515 of the act.
    (16) A Product Development Protocol for a Medical Device, described 
in section 515 of the act.
    (17) Data and information regarding a medical device submitted as 
part of the procedures for classifying such devices, described in part 
860.
    (18) Data and information regarding a medical device submitted as 
part of the procedures for establishing, amending, or repealing a 
performance standard for such devices, described in part 861.
    (19) Data and information regarding an electronic product submitted 
as part of the procedures for obtaining an exemption from notification 
of a radiation safety defect or failure of compliance with a radiation 
safety performance standard, described in subpart D of part 1003.
    (20) Data and information regarding an electronic product submitted 
as part of the procedures for establishing, amending, or repealing a 
standard for such product, described in section 358 of the Public Health 
Service Act.
    (21) Data and information regarding an electronic product submitted 
as part of the procedures for obtaining a variance from any electronic 
product performance standard as described in Sec. 1010.4.
    (22) Data and information regarding an electronic product submitted 
as part of the procedures for granting, amending, or extending an 
exemption from any electronic product performance standard, as described 
in Sec. 1010.5.
    (f) Sponsor means:

[[Page 305]]

    (1) A person who initiates and supports, by provision of financial 
or other resources, a nonclinical laboratory study;
    (2) A person who submits a nonclinical study to the Food and Drug 
Administration 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.
    (g) Testing facility means a person who actually conducts a 
nonclinical laboratory study, i.e., actually uses the test article in a 
test system. Testing facility includes any establishment required to 
register under section 510 of the act that conducts nonclinical 
laboratory studies and any consulting laboratory described in section 
704 of the act that conducts such studies. Testing facility encompasses 
only those operational units that are being or have been used to conduct 
nonclinical laboratory studies.
    (h) Person includes an individual, partnership, corporation, 
association, scientific or academic establishment, government agency, or 
organizational unit thereof, and any other legal entity.
    (i) Test system means any animal, plant, microorganism, or subparts 
thereof to which the test or control article is administered or added 
for study. Test system also includes appropriate groups or components of 
the system not treated with the test or control articles.
    (j) Specimen means any material derived from a test system for 
examination or analysis.
    (k) Raw data means any laboratory worksheets, records, memoranda, 
notes, or exact copies thereof, that are the result of original 
observations and activities of a nonclinical laboratory 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.
    (l) 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 
nonclinical laboratory studies.
    (m) Study director means the individual responsible for the overall 
conduct of a nonclinical laboratory study.
    (n) Batch means a specific quantity or lot of a test or control 
article that has been characterized according to Sec. 58.105(a).
    (o) Study initiation date means the date the protocol is signed by 
the study director.
    (p) Study completion date means the date the final report is signed 
by the study director.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33779, Sept. 4, 1987; 
54 FR 9039, Mar. 3, 1989; 64 FR 56448, Oct. 20, 1999]



21CFR58.10

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.10]

[Page 305]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                      Subpart A--General Provisions
 
Sec. 58.10  Applicability to studies performed under grants and contracts.

    When a sponsor conducting a nonclinical laboratory study intended to 
be submitted to or reviewed by the Food and Drug Administration utilizes 
the services of a consulting laboratory, contractor, or grantee to 
perform an analysis or other service, it shall notify the consulting 
laboratory, contractor, or grantee that the service is part of a 
nonclinical laboratory study that must be conducted in compliance with 
the provisions of this part.



21CFR58.15

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.15]

[Page 305-306]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                      Subpart A--General Provisions
 
Sec. 58.15  Inspection of a testing facility.

    (a) A testing facility shall permit an authorized employee of the 
Food and Drug Administration, 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 within the scope of this part. The records 
inspection and copying requirements shall not apply to quality assurance 
unit records of findings and problems, or to actions recommended and 
taken.

[[Page 306]]

    (b) The Food and Drug Administration will not consider a nonclinical 
laboratory study in support of an application for a research or 
marketing permit if the testing facility refuses to permit inspection. 
The determination that a nonclinical laboratory 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 the Food and Drug Administration.



21CFR58.29

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.29]

[Page 306]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart B--Organization and Personnel
 
Sec. 58.29  Personnel.


    (a) Each individual engaged in the conduct of or responsible for the 
supervision of a nonclinical laboratory 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 nonclinical laboratory 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 and control articles 
and test systems.
    (e) Personnel engaged in a nonclinical laboratory 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 and control articles.
    (f) Any individual found at any time to have an illness that may 
adversely affect the quality and integrity of the nonclinical laboratory 
study shall be excluded from direct contact with test systems, test and 
control articles 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 nonclinical laboratory study.



21CFR58.31

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.31]

[Page 306]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart B--Organization and Personnel
 
Sec. 58.31  Testing facility management.

    For each nonclinical laboratory study, testing facility management 
shall:
    (a) Designate a study director as described in Sec. 58.33, 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. 58.35.
    (d) Assure that test and control articles 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.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]



21CFR58.33

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.33]

[Page 306-307]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart B--Organization and Personnel
 
Sec. 58.33  Study director.

    For each nonclinical laboratory 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. 58.120 and is followed.
    (b) All experimental data, including observations of unanticipated 
responses of the test system are accurately recorded and verified.

[[Page 307]]

    (c) Unforeseen circumstances that may affect the quality and 
integrity of the nonclinical laboratory 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.

[43 FR 60013, Dec. 22, 1978; 44 FR 17657, Mar. 23, 1979]



21CFR58.35

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.35]

[Page 307]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart B--Organization and Personnel
 
Sec. 58.35  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.
    (b) The quality assurance unit shall:
    (1) Maintain a copy of a master schedule sheet of all nonclinical 
laboratory studies conducted at the testing facility indexed by test 
article and containing the test system, nature of study, date study was 
initiated, current status of each study, identity of the sponsor, and 
name of the study director.
    (2) Maintain copies of all protocols pertaining to all nonclinical 
laboratory studies for which the unit is responsible.
    (3) Inspect each nonclinical laboratory study at intervals adequate 
to assure the integrity of the study and maintain written and properly 
signed records of each periodic inspection showing the date of the 
inspection, the study inspected, the phase or segment of the study 
inspected, the person performing the inspection, findings and problems, 
action recommended and taken to resolve existing problems, and any 
scheduled date for reinspection. Any problems found during the course of 
an inspection which are likely to affect study integrity 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 
nonclinical laboratory 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 of the Food and Drug Administration.
    (d) A designated representative of the Food and Drug Administration 
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.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]



21CFR58.41

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.41]

[Page 307-308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart C--Facilities
 
Sec. 58.41  General.


    Each testing facility shall be of suitable size and construction to 
facilitate

[[Page 308]]

the proper conduct of nonclinical laboratory studies. It 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.

[52 FR 33780, Sept. 4, 1987]



21CFR58.43

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.43]

[Page 308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart C--Facilities
 
Sec. 58.43  Animal care facilities.

    (a) A testing facility shall have a sufficient number of animal 
rooms or areas, as needed, to assure proper: (1) Separation of species 
or test systems, (2) isolation of individual projects, (3) quarantine of 
animals, and (4) routine or specialized housing of animals.
    (b) A testing facility shall have a number of animal rooms or areas 
separate from those described in paragraph (a) of this section to ensure 
isolation of studies being done with test systems or test and control 
articles known to be biohazardous, including volatile substances, 
aerosols, radioactive materials, and infectious agents.
    (c) Separate areas shall be provided, as appropriate, for the 
diagnosis, treatment, and control of laboratory animal diseases. These 
areas shall provide effective isolation for the housing of animals 
either known or suspected of being diseased, or of being carriers of 
disease, from other animals.
    (d) When animals are housed, facilities shall exist for the 
collection and disposal of all animal waste and refuse or for safe 
sanitary storage of waste before removal from the testing facility. 
Disposal facilities shall be so provided and operated as to minimize 
vermin infestation, odors, disease hazards, and environmental 
contamination.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]



21CFR58.45

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.45]

[Page 308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart C--Facilities
 
Sec. 58.45  Animal supply facilities.

    There shall be storage areas, as needed, for feed, bedding, 
supplies, and equipment. Storage areas for feed and bedding shall be 
separated from areas housing the test systems and shall be protected 
against infestation or contamination. Perishable supplies shall be 
preserved by appropriate means.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]



21CFR58.47

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.47]

[Page 308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart C--Facilities
 
Sec. 58.47  Facilities for handling test and control articles.

    (a) As necessary to prevent contamination or mixups, there shall be 
separate areas for:
    (1) Receipt and storage of the test and control articles.
    (2) Mixing of the test and control articles with a carrier, e.g., 
feed.
    (3) Storage of the test and control article mixtures.
    (b) Storage areas for the test and/or control article and test and 
control mixtures shall be separate from areas housing the test systems 
and shall be adequate to preserve the identity, strength, purity, and 
stability of the articles and mixtures.



21CFR58.49

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.49]

[Page 308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart C--Facilities
 
Sec. 58.49  Laboratory operation areas.

    Separate laboratory space shall be provided, as needed, for the 
performance of the routine and specialized procedures required by 
nonclinical laboratory studies.

[52 FR 33780, Sept. 4, 1987]



21CFR58.51

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.51]

[Page 308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart C--Facilities
 
Sec. 58.51  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.



21CFR58.61

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.61]

[Page 308]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart D--Equipment
 
Sec. 58.61  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.

[52 FR 33780, Sept. 4, 1987]



21CFR58.63

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.63]

[Page 308-309]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                          Subpart D--Equipment
 
Sec. 58.63  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. 58.81(b)(11)

[[Page 309]]

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.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]



21CFR58.81

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.81]

[Page 309]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                 Subpart E--Testing Facilities Operation
 
Sec. 58.81  Standard operating procedures.


    (a) A testing facility shall have standard operating procedures in 
writing setting forth nonclinical laboratory 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) Animal room preparation.
    (2) Animal care.
    (3) Receipt, identification, storage, handling, mixing, and method 
of sampling of the test and control articles.
    (4) Test system observations.
    (5) Laboratory tests.
    (6) Handling of animals found moribund or dead during study.
    (7) Necropsy of animals or postmortem examination of animals.
    (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 animals.
    (c) Each laboratory area shall have immediately available laboratory 
manuals and standard operating procedures relative to the laboratory 
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.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]



21CFR58.83

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.83]

[Page 309]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                 Subpart E--Testing Facilities Operation
 
Sec. 58.83  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.



21CFR58.90

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.90]

[Page 309-310]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                 Subpart E--Testing Facilities Operation
 
Sec. 58.90  Animal care.

    (a) There shall be standard operating procedures for the housing, 
feeding, handling, and care of animals.
    (b) All newly received animals from outside sources shall be 
isolated and their health status shall be evaluated in accordance with 
acceptable veterinary medical practice.
    (c) At the initiation of a nonclinical laboratory study, animals 
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 
animals contract such a disease or condition, the diseased animals shall 
be isolated, if necessary. These animals may be treated for disease or 
signs of disease provided that

[[Page 310]]

such treatment does not interfere with the study. The diagnosis, 
authorizations of treatment, description of treatment, and each date of 
treatment shall be documented and shall be retained.
    (d) Warm-blooded animals, excluding suckling rodents, used in 
laboratory procedures that require manipulations and observations over 
an extended period of time or in studies that require the animals to be 
removed from and returned to their home cages for any reason (e.g., cage 
cleaning, treatment, etc.), shall receive appropriate identification. 
All information needed to specifically identify each animal within an 
animal-housing unit shall appear on the outside of that unit.
    (e) Animals of different species shall be housed in separate rooms 
when necessary. Animals of the same species, but used in different 
studies, should not ordinarily be housed in the same room when 
inadvertent exposure to control or test articles or animal mixup could 
affect the outcome of either study. If such mixed housing is necessary, 
adequate differentiation by space and identification shall be made.
    (f) Animal cages, racks and accessory equipment shall be cleaned and 
sanitized at appropriate intervals.
    (g) Feed and water used for the animals 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 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.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987; 
54 FR 15924, Apr. 20, 1989; 56 FR 32088, July 15, 1991]



21CFR58.105

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.105]

[Page 310]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart F--Test and Control Articles
 
Sec. 58.105  Test and control article characterization.


    (a) The identity, strength, purity, and composition or other 
characteristics which will appropriately define the test or control 
article shall be determined for each batch and shall be documented. 
Methods of synthesis, fabrication, or derivation of the test and control 
articles shall be documented by the sponsor or the testing facility. In 
those cases where marketed products are used as control articles, such 
products will be characterized by their labeling.
    (b) The stability of each test or control article shall be 
determined by the testing facility or by the sponsor either: (1) Before 
study initiation, or (2) concomitantly according to written standard 
operating procedures, which provide for periodic analysis of each batch.
    (c) Each storage container for a test or control article shall be 
labeled by name, chemical abstract number 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 or control article. Storage containers shall be assigned to a 
particular test article for the duration of the study.
    (d) For studies of more than 4 weeks' duration, reserve samples from 
each batch of test and control articles shall be retained for the period 
of time provided by Sec. 58.195.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]



21CFR58.107

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.107]

[Page 310-311]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart F--Test and Control Articles
 
Sec. 58.107  Test and control article handling.

    Procedures shall be established for a system for the handling of the 
test and control articles 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.

[[Page 311]]

    (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.



21CFR58.113

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.113]

[Page 311]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                  Subpart F--Test and Control Articles
 
Sec. 58.113  Mixtures of articles with carriers.

    (a) For each test or control article 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 or control article in the 
mixture.
    (2) To determine the stability of the test and control articles in 
the mixture as required by the conditions of the study either:
    (i) Before study initiation, or
    (ii) Concomitantly according to written standard operating 
procedures which provide for periodic analysis of the test and control 
articles in the mixture.
    (b) [Reserved]
    (c) Where any of the components of the test or control article 
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.

[43 FR 60013, Dec. 22, 1978, as amended at 45 FR 24865, Apr. 11, 1980; 
52 FR 33781, Sept. 4, 1987]



21CFR58.120

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.120]

[Page 311]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
  Subpart G--Protocol for and Conduct of a Nonclinical Laboratory Study
 
Sec. 58.120  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, as applicable, the following information:
    (1) A descriptive title and statement of the purpose of the study.
    (2) Identification of the test and control articles by name, 
chemical abstract number, or code number.
    (3) The name of the sponsor and the name and address of the testing 
facility at which the study is being conducted.
    (4) The number, body weight range, sex, source of supply, species, 
strain, substrain, and age of the test system.
    (5) The procedure for identification of the test system.
    (6) A description of the experimental design, including the methods 
for the control of bias.
    (7) A description and/or identification of the diet used in the 
study as well as solvents, emulsifiers, and/or other materials used to 
solubilize or suspend the test or control articles before mixing with 
the carrier. The description shall include specifications for acceptable 
levels of contaminants that are reasonably expected to be present in the 
dietary materials and are known to be capable of interfering with the 
purpose or conduct of the study if present at levels greater than 
established by the specifications.
    (8) Each dosage level, expressed in milligrams per kilogram of body 
weight or other appropriate units, of the test or control article to be 
administered and the method and frequency of administration.
    (9) The type and frequency of tests, analyses, and measurements to 
be made.
    (10) The records to be maintained.
    (11) The date of approval of the protocol by the sponsor and the 
dated signature of the study director.
    (12) A statement of the proposed statistical methods to be used.
    (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.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]



21CFR58.130

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.130]

[Page 311-312]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
  Subpart G--Protocol for and Conduct of a Nonclinical Laboratory Study
 
Sec. 58.130  Conduct of a nonclinical laboratory study.

    (a) The nonclinical laboratory 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

[[Page 312]]

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) Records of gross findings for a specimen from postmortem 
observations should be available to a pathologist when examining that 
specimen histopathologically.
    (e) All data generated during the conduct of a nonclinical 
laboratory study, except those that are generated by automated data 
collection systems, shall be recorded directly, promptly, and legibly in 
ink. All data entries shall be dated on the date of entry and signed or 
initialed by the person entering the data. Any change in entries shall 
be made so as not to obscure the original entry, shall indicate the 
reason for such change, and shall be dated and signed or identified at 
the time of the change. In automated data collection systems, the 
individual responsible for direct data input shall be identified at the 
time of data input. Any change in automated data entries shall be made 
so as not to obscure the original entry, shall indicate the reason for 
change, shall be dated, and the responsible individual shall be 
identified.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]

Subparts H-I  [Reserved]



21CFR58.185

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.185]

[Page 312]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                     Subpart J--Records and Reports
 
Sec. 58.185  Reporting of nonclinical laboratory study results.


    (a) A final report shall be prepared for each nonclinical laboratory 
study and shall include, but not necessarily be limited to, the 
following:
    (1) Name and address of the facility performing the study and the 
dates on which the study was initiated and completed.
    (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 and control articles identified by name, chemical 
abstracts number or code number, strength, purity, and composition or 
other appropriate characteristics.
    (5) Stability of the test and control articles 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 cirmcumstances 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.
    (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. 58.35(b)(7).
    (b) The final report shall be signed and dated by the study 
director.
    (c) Corrections or additions to a final report shall be in the form 
of an amendment by the study director. The amendment shall clearly 
identify that part of the final report that is being added to or 
corrected and the reasons for the correction or addition, and shall be 
signed and dated by the person responsible.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]

[[Page 313]]



21CFR58.190

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.190]

[Page 313]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                     Subpart J--Records and Reports
 
Sec. 58.190  Storage and retrieval of records and data.

    (a) All raw data, documentation, protocols, final reports, and 
specimens (except those specimens obtained from mutagenicity tests and 
wet specimens of blood, urine, feces, and biological fluids) generated 
as a result of a nonclinical laboratory study 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 or 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.

(Information collection requirements approved by the Office of 
Management and Budget under control number 0910-0203)

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]



21CFR58.195

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.195]

[Page 313-314]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
                     Subpart J--Records and Reports
 
Sec. 58.195  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 chapter.
    (b) Except as provided in paragraph (c) of this section, 
documentation records, raw data and specimens pertaining to a 
nonclinical laboratory study and required to be made by this part shall 
be retained in the archive(s) for whichever of the following periods is 
shortest:
    (1) A period of at least 2 years following the date on which an 
application for a research or marketing permit, in support of which the 
results of the nonclinical laboratory study were submitted, is approved 
by the Food and Drug Administration. This requirement does not apply to 
studies supporting investigational new drug applications (IND's) or 
applications for investigational device exemptions (IDE's), records of 
which shall be governed by the provisions of paragraph (b)(2) of this 
section.
    (2) A period of at least 5 years following the date on which the 
results of the nonclinical laboratory study are submitted to the Food 
and Drug Administration in support of an application for a research or 
marketing permit.
    (3) In other situations (e.g., where the nonclinical laboratory 
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 (except those specimens obtained from mutagenicity 
tests and wet specimens of blood, urine, feces, and biological fluids), 
samples of test or control articles, 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. In no case shall retention be 
required for longer periods than those set forth in paragraphs (a) and 
(b) of this section.
    (d) The master schedule sheet, copies of protocols, and records of 
quality assurance inspections, as required by Sec. 58.35(c) shall be 
maintained by the quality assurance unit as an easily accessible system 
of records for the period of time specified in paragraphs (a) and (b) of 
this section.
    (e) Summaries of training and experience and job descriptions 
required to be maintained by Sec. 58.29(b) may be retained along with 
all other testing facility employment records for the length of time 
specified in paragraphs (a) and (b) of this section.
    (f) Records and reports of the maintenance and calibration and 
inspection of equipment, as required by Sec. 58.63(b) and (c), shall be 
retained for the length of time specified in paragraph (b) of this 
section.

[[Page 314]]

    (g) 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.
    (h) If a facility conducting nonclinical testing 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 Food and Drug Administration shall be notified in writing of 
such a transfer.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 
54 FR 9039, Mar. 3, 1989]



21CFR58.200

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.200]

[Page 314]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.200  Purpose.


    (a) The purposes of disqualification are:
    (1) To permit the exclusion from consideration of completed studies 
that were conducted by a testing facility which has failed to comply 
with the requirements of the good laboratory practice regulations until 
it can be adequately demonstrated that such noncompliance did not occur 
during, or did not affect the validity or acceptability of data 
generated by, a particular study; and
    (2) To exclude from consideration all studies completed after the 
date of disqualification until the facility can satisfy the Commissioner 
that it will conduct studies in compliance with such regulations.
    (b) The determination that a nonclinical laboratory study may 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 other applicable regulation to submit the results 
of the study to the Food and Drug Administration.



21CFR58.202

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.202]

[Page 314]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.202  Grounds for disqualification.

    The Commissioner may disqualify a testing facility upon finding all 
of the following:
    (a) The testing facility failed to comply with one or more of the 
regulations set forth in this part (or any other regulations regarding 
such facilities in this chapter);
    (b) The noncompliance adversely affected the validity of the 
nonclinical laboratory studies; and
    (c) Other lesser regulatory actions (e.g., warnings or rejection of 
individual studies) have not been or will probably not be adequate to 
achieve compliance with the good laboratory practice regulations.



21CFR58.204

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.204]

[Page 314]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.204  Notice of and opportunity for hearing on proposed disqualification.

    (a) Whenever the Commissioner has information indicating that 
grounds exist under Sec. 58.202 which in his opinion justify 
disqualification of a testing facility, he may issue to the testing 
facility a written notice proposing that the facility be disqualified.
    (b) A hearing on the disqualification shall be conducted in 
accordance with the requirements for a regulatory hearing set forth in 
part 16 of this chapter.



21CFR58.206

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.206]

[Page 314]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.206  Final order on disqualification.

    (a) If the Commissioner, after the regulatory hearing, or after the 
time for requesting a hearing expires without a request being made, upon 
an evaulation of the administrative record of the disqualification 
proceeding, makes the findings required in Sec. 58.202, he shall issue a 
final order disqualifying the facility. Such order shall include a 
statement of the basis for that determination. Upon issuing a final 
order, the Commissioner shall notify (with a copy of the order) the 
testing facility of the action.
    (b) If the Commissioner, after a regulatory hearing or after the 
time for requesting a hearing expires without a request being made, upon 
an evaluation of the administrative record of the disqualification 
proceeding, does not make the findings required in Sec. 58.202, he shall 
issue a final order terminating the disqualification proceeding. Such 
order shall include a statement of the basis for that determination. 
Upon issuing a final order the Commissioner shall notify the testing 
facility and provide a copy of the order.

[[Page 315]]



21CFR58.210

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.210]

[Page 315]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.210  Actions upon disqualification.

    (a) Once a testing facility has been disqualified, each application 
for a research or marketing permit, whether approved or not, containing 
or relying upon any nonclinical laboratory study conducted by the 
disqualified testing facility may be examined to determine whether such 
study was or would be essential to a decision. If it is determined that 
a study was or would be essential, the Food and Drug Administration 
shall also determine whether the study is acceptable, notwithstanding 
the disqualification of the facility. Any study done by a testing 
facility before or after disqualification may be presumed to be 
unacceptable, and the person relying on the study may be required to 
establish that the study was not affected by the circumstances that led 
to the disqualification, e.g., by submitting validating information. If 
the study is then determined to be unacceptable, such data will be 
eliminated from consideration in support of the application; and such 
elimination may serve as new information justifying the termination or 
withdrawal of approval of the application.
    (b) No nonclinical laboratory study begun by a testing facility 
after the date of the facility's disqualification shall be considered in 
support of any application for a research or marketing permit, unless 
the facility has been reinstated under Sec. 58.219. The determination 
that a study may 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 other applicable 
regulation to submit the results of the study to the Food and Drug 
Administration.

[43 FR 60013, Dec. 22, 1978, as amended at 59 FR 13200, Mar. 21, 1994]



21CFR58.213

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.213]

[Page 315]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.213  Public disclosure of information regarding disqualification.

    (a) Upon issuance of a final order disqualifying a testing facility 
under Sec. 58.206(a), the Commissioner may notify all or any interested 
persons. Such notice may be given at the discretion of the Commissioner 
whenever he believes that such disclosure would further the public 
interest or would promote compliance with the good laboratory practice 
regulations set forth in this part. Such notice, if given, shall include 
a copy of the final order issued under Sec. 58.206(a) and shall state 
that the disqualification constitutes a determination by the Food and 
Drug Administration that nonclinical laboratory studies performed by the 
facility will not be considered by the Food and Drug Administration in 
support of any application for a research or marketing permit. If such 
notice is sent to another Federal Government agency, the Food and Drug 
Administration will recommend that the agency also consider whether or 
not it should accept nonclinical laboratory studies performed by the 
testing facility. If such notice is sent to any other person, it shall 
state that it is given because of the relationship between the testing 
facility and the person being notified and that the Food and Drug 
Administration is not advising or recommending that any action be taken 
by the person notified.
    (b) A determination that a testing facility has been disqualified 
and the administrative record regarding such determination are 
disclosable to the public under part 20 of this chapter.



21CFR58.215

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.215]

[Page 315-316]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.215  Alternative or additional actions to disqualification.

    (a) Disqualification of a testing facility under this subpart is 
independent of, and neither in lieu of nor a precondition to, other 
proceedings or actions authorized by the act. The Food and Drug 
Administration may, at any time, institute against a testing facility 
and/or against the sponsor of a nonclinical laboratory study that has 
been submitted to the Food and Drug Administration any appropriate 
judicial proceedings (civil or criminal) and any other appropriate 
regulatory action, in addition to or in lieu of, and prior to, 
simultaneously with, or subsequent to, disqualification. The Food and 
Drug Administration may also refer the matter to another Federal, State, 
or local government law enforcement or regulatory agency for such action 
as that agency deems appropriate.
    (b) The Food and Drug Administration may refuse to consider any 
particular nonclinical laboratory study in

[[Page 316]]

support of an application for a research or marketing permit, if it 
finds that the study was not conducted in accordance with the good 
laboratory practice regulations set forth in this part, without 
disqualifying the testing facility that conducted the study or 
undertaking other regulatory action.



21CFR58.217

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.217]

[Page 316]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.217  Suspension or termination of a testing facility by a sponsor.

    Termination of a testing facility by a sponsor is independent of, 
and neither in lieu of nor a precondition to, proceedings or actions 
authorized by this subpart. If a sponsor terminates or suspends a 
testing facility from further participation in a nonclinical laboratory 
study that is being conducted as part of any application for a research 
or marketing permit that has been submitted to any Center of the Food 
and Drug Administration (whether approved or not), it shall notify that 
Center in writing within 15 working days of the action; the notice shall 
include a statement of the reasons for such action. Suspension or 
termination of a testing facility by a sponsor does not relieve it of 
any obligation under any other applicable regulation to submit the 
results of the study to the Food and Drug Administration.

[43 FR FR 60013, Dec. 22, 1978, as amended at 50 FR 8995, Mar. 6, 1985]



21CFR58.219

[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR58.219]

[Page 316]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES--Table of Contents
 
            Subpart K--Disqualification of Testing Facilities
 
Sec. 58.219  Reinstatement of a disqualified testing facility.

    A testing facility that has been disqualified may be reinstated as 
an acceptable source of nonclinical laboratory studies to be submitted 
to the Food and Drug Administration if the Commissioner determines, upon 
an evaluation of the submission of the testing facility, that the 
facility can adequately assure that it will conduct future nonclinical 
laboratory studies in compliance with the good laboratory practice 
regulations set forth in this part and, if any studies are currently 
being conducted, that the quality and integrity of such studies have not 
been seriously compromised. A disqualified testing facility that wishes 
to be so reinstated shall present in writing to the Commissioner reasons 
why it believes it should be reinstated and a detailed description of 
the corrective actions it has taken or intends to take to assure that 
the acts or omissions which led to its disqualification will not recur. 
The Commissioner may condition reinstatement upon the testing facility 
being found in compliance with the good laboratory practice regulations 
upon an inspection. If a testing facility is reinstated, the 
Commissioner shall so notify the testing facility and all organizations 
and persons who were notified, under Sec. 58.213 of the disqualification 
of the testing facility. A determination that a testing facility has 
been reinstated is disclosable to the public under part 20 of this 
chapter.



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