The latest version of this guidance was issued in November 2003.

Guidelines for reporting the results of toxicity studies are contained in this section. More complete information regarding Pathology and Statistics can be found in Chapters IV B 3c and IV B 4a, respectively.

1.  Identification

   1.  Each study report should be signed by the persons responsible for the study, and should identify:

      1.  the laboratory (i.e., name and address) where the study was performed;

      2.  the inclusive dates of the study; and

      3.  primary person responsible for each component of the study, including: 1) Study Director, 2) Pathologist, 3) Data Analyst, 4) Authors, and 5) Other major contributors to the report.

2.  Good Laboratory Practice for Nonclinical Laboratory Studies

   The Good Laboratory Practice Regulations (GLP's) were designed to establish basic standards for conduct and reporting of nonclinical safety testing and are intended to assure the quality and integrity of safety data submitted to the FDA. Each nonclinical toxicity study submitted to the Agency should include either a signed statement that the study was conducted in compliance with Good Laboratory Practice Regulations, as specified in Section 21 of the U.S. Code of Federal Regulations (CFR) 58, or, if the study was not conducted in compliance with GLP's, a signed statement including a list of the specific area(s) of noncompliance and the reason(s) for the noncompliance. Each study report should also include a signed record of periodic inspections conducted by the Quality Assurance Unit (QAU) showing the date of the inspection, the phase or segment of the study inspected, and the date the findings were reported to management.

3.  Body of Report

   The study report should include all information necessary to provide a complete and accurate description and evaluation of the study procedures and results. The following sections should be included:

   1.  Protocol and Amendments

      Under GLP, each non-clinical study requires a written protocol that clearly indicates the objectives and methods for the conduct of the study. The protocol should satisfy all GLP requirements set forth in Section 21 of CFR § 58.120, including all changes in or revisions of the protocol and the reasons for those changes.

   2. Summary and Conclusions

      This section of the study report should contain a brief description of the methods, summary of the data, analysis of the data, and a statement of the conclusions drawn from the analysis.

      The summary should highlight all data, observations and deviations from control data which may indicate toxic effects of the test substance.

      The summary should include a description of all circumstances that may have affected the quality or integrity of the data.

   3. Materials

      The materials section of the study report should include, but not be limited to, the following information:

      1.  Test substance

         1. Chemical name, Chemical Abstracts Service (CAS) registry number (or code number), molecular structure, and a qualitative and quantitative determination of its chemical composition, including names and quantities of known contaminants and impurities and the percentage of unidentifiable materials;

         2. Manufacturer and lot number of the substance tested, and such information as physical state, solubility (aqueous and in dosing vehicle), pH (pKa where applicable), stability, purity, and expiration date;

         3. Exact identification of diluents, suspending agents, emulsifiers, excipients, or other materials used in administering the test substance.

         4. Storage

      2. Animal data
         1. Species and strain (and substrain if applicable) used and, particularly if a strain other than a common laboratory strain is used in the study, rationale for selection of the strain;

         2. Source of supply of the animals;

         3. Description of any pre-test conditioning (such as quarantine procedures);

         4. Description of the method used to randomize animals into test and control groups; and

         5. Numbers, age, and condition of animals of each sex in all test and control groups at the beginning of the study.

         6. Data derived from and fate of, each individual animal in the study.

         7. Feed and water information, including diet (lot number, composition, etc.) and availability

      3. Data on experimental facilities
         1. Descriptions of the caging condition, including number of animals per cage, bedding material, ambient temperature, humidity, and lighting conditions.

   4. Methods
      1. The methods section of the study report should include, but not be limited to, the following information:
         1. Deviation from guidelines: This section should indicate all ways in which the test procedure deviates from these guidelines and should state the rationale for each deviation.

         2. Specification of test methods: This section should include a full description of the experimental design and procedures, the length of the study, and the dates on which the study began and ended.

         3. Statistical analyses: All statistical methods used should be fully described or identified by reference. For a complete discussion of the information that should be contained in this section of the study report, see Chapter IV B 4.

         4. Data on dosage administration:
            1. All dose levels administered, expressed as mg/kg body weight, per unit of time;

            2. Method, frequency, and time of day of administration; and

            3. Total volume or dose plus vehicle administered to each animal, if the test substance is administered by gavage; and

            4. Duration of treatment period.
         5. Data on observation methods:
            1. Duration; and

            2. Method and frequency of observation of the test animals.

   5. Results
      1. Each study report must include individual animal data and results, and tabulation of data must be provided in sufficient detail to permit independent evaluation of the results.

         The following information should be included for each test animal, where appropriate:

         1. Time of first observation of each abnormal sign and its subsequent course; (Toxic response data should be organized, when appropriate, by litter.)

         2. Time of death during the study for each test animal; (For those animals that are not sacrificed on schedule, cause of death should be determined and reported, if possible.)

         3. Feed consumption data (and water consumption data, if the test compound is administered in the drinking water) for each animal;

         4. Body weights and body weight changes;

         5. Hematology, clinical chemistry, and other clinical findings;

         6. Results of neurotoxicity and immunotoxicity studies, as appropriate;

         7. Gross necropsy findings including description and incidence of gross lesions; and

         8. Histopathology findings, including description and incidence of microscopic lesions.

      2. Data also should be summarized in tabular form, organized by sex and dose group. When appropriate, data should also be organized by litter. When numerical means are presented, they should be accompanied by an appropriate measure of variability, such as the standard error. For each summarized parameter, the following information should be included:
         1. The number of animals at the beginning of the study

         2. The number of animals evaluated for each parameter

         3. The time when animals were evaluated for each parameter

         4. The number and percentage of animals positive and/or negative for each parameter in comparision to controls.

      3. All numerical results should be evaluated by an appropriate statistical method. Refer to Chapter IV B 4 for detailed guidelines about statistical considerations in toxicity studies.

      4. Evaluation of the results should include:
         1. Statements about the nature of relationships, if any, between exposure to the test substance and the incidence and severity of all general and specific toxic effects (such as neoplastic and non-neoplastic lesions, organ weight effects, and mortality effects).

         2. Statements about the relationship between clinical observations made during the course of a study and post mortem findings.

         3. An indication of the dosage level at which no toxic effects attributable to the test substance were observed.

   6. References

      This section of the study report should include the following information:

      1. Availability of original data, specimens and samples of the test substance; location of all original data, specimens, and samples of the test substance.

      2. Literature or references, including, when appropriate, references for: test procedures; statistical and other methods used to analyze the data; compilation and evaluation of results; and the basis upon which conclusions were reached.