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  5. Facility Operation
  1. FDA Bioresearch Monitoring Information

Facility Operation

Comparison of FDA, EPA, OECD GLP Facility Operation
Topic FDA EPA OECD
Standard
Operating
Procedures
(SOPs)		 58.81
(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.		 792.81
(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.		 Section II
7.1. A test facility should have written Standard Operating Procedures approved by test facility management that are intended to ensure the quality and integrity of the data generated by that test facility.
Deviations
from SOPs		 58.81
(a) All deviations in a study from standard operating procedures shall be authorized by the study director and shall be documented in the raw data.		 792.81
(a) All deviations in a study from standard operating procedures shall be authorized by the study director and shall be documented in the raw data.		 Section II
7.3. Deviations from Standard Operating Procedures related to the study should be documented and should be acknowledged by the Study Director and the Principal Investigator(s), as applicable.
Changes in
SOPs		 58.81
(a) Significant changes in established standard operating procedures shall be properly authorized in writing by management.		 792.81
(a) Significant changes in established standard operating procedures shall be properly authorized in writing by management.		 Section II
7.1. Revisions to Standard Operating Procedures should be approved by test facility management.
Required SOPs

58.81
(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.

792.81
(b) Standard operating procedures shall be established
for, but not limited to, the following:

  1. Test system room preparation.
  2. Test system care.
  3. Receipt, identification, storage, handling, mixing, and method of sampling of the test, control, and reference substances.
  4. Test system observations.
  5. Laboratory or other tests.
  6. Handling of test systems found moribund or dead during study.
  7. Necropsy of test systems or postmortem examination
    of test systems.
  8. Collection and identification of specimens.
  9. Histopathology.
  10. Data handling, storage and retrieval.
  11. Maintenance and calibration of equipment.
  12. Transfer, proper placement, and identification of test systems.

Section II
7.4. Standard Operating Procedures should be available for, but not be limited to, the following categories of test facility activities. The details given under each heading are to be considered as illustrative examples.

  1. Test and Reference Items
    Receipt, identification, labelling, handling, sampling and
    storage.
  2. Apparatus, Materials and Reagents
    1. Apparatus Use, maintenance, cleaning and calibration.
    2. Computerised Systems Validation, operation, maintenance, security, change
      control and back-up.
    3. Materials, Reagents and Solutions Preparation and labelling.
  3. Record Keeping, Reporting, Storage, and Retrieval
    Coding of studies, data collection, preparation of
    reports, indexing systems, handling of data, including the
    use of computerised systems.
  4. Test System (where appropriate)
    1. Room preparation and environmental room conditions for the test system.
    2. Procedures for receipt, transfer, proper placement, characterisation, identification and care of the test system.
    3. Test system preparation, observations and examinations, before, during and at the conclusion of the study.
    4. Handling of test system individuals found moribund or dead during the study.
    5. Collection, identification and handling of specimens including necropsy and histopathology.
    6. Siting and placement of test systems in test plots.
  5. Quality Assurance Procedures Operation of Quality Assurance personnel in planning, scheduling, performing, documenting and reporting inspections.
Availability of
SOPs		 58.81
(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.		 792.81
(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.		 Section II
7.2. Each separate test facility unit or area should have immediately available current Standard Operating Procedures
relevant to the activities being performed therein. Published text books, analytical methods, articles and manuals may be used as supplements to these Standard Operating Procedures.
Historical file of
SOPs		 58.81
(d) A historical file of standard operating procedures, and all revisions thereof, including the dates of such revisions, shall be maintained.		 792.81
(d) A historical file of standard operating procedures, and all revisions thereof, including the dates of such revisions, shall be maintained.		 Section II
10.1.
(f) The historical file of all Standard Operating Procedures;
Labeling of
Reagents		 58.83
All reagents and solutions in the laboratory areas shall be labeled to indicate identity, titer or concentration, storage requirements, and expiration date. Deteriorated or outdated reagents and solutions shall not be used.		 792.83
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.		 Section II
4.4. Chemicals, reagents, and solutions should be labelled to indicate identity (with concentration if appropriate), expiry date and specific storage instructions. Information concerning source, preparation date and stability should be available. The expiry date
may be extended on the basis of documented evaluation or analysis.
Records of Test
System Receipt		     Section II
5.2.3. Records of source, date of arrival, and arrival condition of test systems should be maintained.
Test System
Care SOPs		 58.90
(a) There shall be standard operating procedures for the housing, feeding, handling, and care of animals.		 792.90
(a) There shall be standard operating procedures for the housing, feeding, handling, and care of animals and other test systems.		 Section II
5.2.1. Proper conditions should be established and maintained for the storage, housing, handling and care of biological test systems, in order to ensure the quality of the data.
Isolation of
New Test
Systems		 58.90
(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.		 792.90
(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.		 Section II
5.2.2. Newly received animal and plant test systems should be isolated until their health status has been evaluated. If any unusual mortality or morbidity occurs, this lot should not be used in studies and, when appropriate, should be humanely destroyed. At the experimental starting date of a study, test systems should be free of any disease or condition that might interfere with the purpose or conduct of the study. Test systems that become diseased or injured during the course of a study should be isolated and treated, if necessary to maintain the integrity of the study. Any diagnosis and treatment of any disease before or during a study should be recorded.
Test System
Disease
Conditions		 58.90
(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 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.		 792.90
(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.		 Section II
5.2.2. At the experimental starting date of a study, test systems should be free of any disease or condition that might interfere with the purpose or conduct of the study. Test systems that become diseased or injured during the course of a study should be isolated and treated, if necessary to maintain the integrity of the study. Any diagnosis and treatment of any disease before or during a study should be recorded.
Test System
Identifcation		 58.90
(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		 792.90
(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.		 Section II
5.2.5. All information needed to properly identify the test systems should appear on their housing or containers. Individual test systems that are to be removed from their housing or containers during the conduct of the study should bear appropriate identification, wherever possible.
Housing of Test
Systems		 58.90
(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.

792.90
(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 thesame species, but used in different studies, should not ordinarily be housed in the same room when inadvertent exposure to test, control, or reference substances or test system mixup could affect the outcome of either study. If such mixed housing is necessary, adequate differentiation by space and identification shall be made.

  1. Plants, invertebrate animals, aquatic vertebrate animals, and organisms that may be used in multispecies tests need not be housed in separate rooms, provided that they are adequately segregated to avoid mixup and cross contamination.
 Section II
5.2.1. Proper conditions should be established and maintained for the storage, housing, handling and care of biological test systems, in order to ensure the quality of the data.
5.2.7. Test systems used in field studies should be located so as to avoid interference in the study from spray drift and from past usage of pesticides.
Cleaning of
Cages &
Equipment		 58.90
(f) Animal cages, racks and accessory equipment shall be cleaned and sanitized at appropriate intervals.		 792.90
(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.		 Section II
5.2.6. During use, housing or containers for test systems should be cleaned and sanitised at appropriate intervals. Any material that comes into contact with the test system should be free of contaminants at levels that would interfere with the study. Bedding for animals should be changed as required by sound husbandry practice. Use of pest control agents should be documented.
Animal Feed &
Water		 58.90
(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.		 792.90
(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.		 Section II
5.2.6. Any material that comes into contact with the test system should be free of contaminants at levels that would interfere with the study.
Animal
Bedding		 58.90
(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.		 792.90
(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.		 Section II
5.2.6. Any material that comes into contact with the test system should be free of contaminants at levels that would interfere with the study. Bedding for animals should be changed as required by sound husbandry practice.
Pest Control
Program		 58.90
(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.		 792.90
(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.		 Section II
5.2.6. Use of pest control agents should be documented.
Acclimation of
Test System		   792.90
(j) All plant and animal test systems shall be acclimatized to the environmental conditions of the test, prior to their use in a study.		 Section II
5.2.4. Biological test systems should be acclimatised to the test environment for an adequate period before the first administration/application of the test or reference item.
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