Description
This guideline describes an acceptable format for organizing and presenting the pharmacology and toxicology data required under 21 CF 314.50(d)(2), and any related date, in the nonclinical section of the application. These recommendations pertain only to organization of existing data. This guideline is not intended to affect documentation required by the Good Laboratory Practices (GLP) reporting regulations under 21 CFR 58.185, nor does it describe the specific stufy requirements for particular therapeutic uses or regimens: these are addressed in other guidelines.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Stakeholders
4Entity responsible for submitting applications under section 524B
Entity responsible for printing the document
Entity establishing competence in the use of the assay
The name, title, address, and telephone number of the person FDA may contact
Regulatory Context
Regulatory Activities
2Investigational New Drug submissions
New Drug Application
Document Types
10General principles apply to the submission of all pharmacology and toxicology studies
Summary table format for toxicity and carcinogenicity data
Absorption, Distribution, Metabolism, Excretion studies organization
Results of available studies should be tabulated
paternal effects in Segment I study
The pathology table should identify organs, tissues, and lesions.; Table 3 showing number of tumor-bearing animals
Submission contains a Table of Contents
Studies related to therapeutic indication and adverse reactions
Studies describing toxic signs and lethal dose data
Long-term studies grouped by species and duration
Attributes
10Drug doses should be expressed on a body weight basis
Control group expected to show response (n=50)
Control group in the current study (n=50)
Reference data from previous studies (n=500)
Report the prevalence rate of nonfatal tumors.
Single cohort studies can measure incidence
An assessment of the malignancy of the tumor.; Column in carcinogenicity study data chronology listing
Approximate or calculated median or limit doses
Pharmacodynamic median effective dose
reason to express doses in some other way
Technical Details
Substances
5Tested if they occur as residues in food and have structural alerts
Substance used to deliver the drug
Basis for determining drug sameness
Active ingredient in the CGT product
Studies with a radioactive drug should indicate the molecular location
Testing Methods
10Chemical analysis of blood samples
Order of presentation for mutagenicity studies
Order of presentation for mutagenicity studies
Used to evaluate compatibility with blood for intravenous products.
Special toxicity studies include topical irritation studies.
Special toxicity studies include parenteral irritation studies.
Procedure for D. immitis worm counts
Used for analyzing study data
Monitoring required when concomitant use is unavoidable.
Clinical data required for safety evaluation
Processes
10Procedure where worms are identified and counted for effectiveness calculations.
Segment III of reproduction studies.
Segment II of reproduction studies.
Segment I of reproduction studies.
Include studies appropriate to a particular formulation or route of administration.
Method of oral administration in carcinogenicity studies; oral administration method in Lijinsky study; method of administration in NTP studies for p-chloroaniline; administration in the feed to rats and mice or by gavage; Route of administration in short-term carcinogenicity models; oral route of administration for carcinogenicity studies; Oral gavage study of Wester et al.; Method of administration in carcinogenicity study; Method of administration in NTP studies; Hydrazine sulfate was adminis
study reports should include description of pathologic diagnosis procedures
Overview of nonclinical assessments including Pharmacology Studies
Nonclinical safety assessment
Subchronic, Chronic, Carcinogenicity
Clinical Concepts
10Data base should document relevant observations for each animal including toxic signs
Organ evaluated for microscopic findings
Specific tumor type observed in the liver
Specific tumor type observed in the liver
Reporting the number of animals with tumors in study groups
Data element for carcinogenicity study reporting
Observations recorded for fetuses grouped by litter
Observations recorded for fetuses grouped by litter
P is the proportion of animals with the specified tumor type observed at a certain dose.
Maintain consistency of order of presentation of non-neoplastic and neoplastic pathology.
Standards & References
External Standards
1Standard abbreviations acceptable to a refereed U.S. pharmacology/toxicology journal
Specifications
1For each tumor found to be statistically significant at the p = .05 level.
Related CFR Sections (1)
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Mid-Link Testing Company, Ltd
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Sanitation & Environmental Technology Institute dba SDWH
- 2023-10-31
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Samm Solutions, Inc., d.b.a. BTS Research
Related Warning Letters (9)
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Mid-Link Testing Company, Ltd
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Sanitation & Environmental Technology Institute dba SDWH
- 2023-10-31
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Samm Solutions, Inc., d.b.a. BTS Research
- 2022-08-09
Bioresearch Monitoring Program
Valley Biosystems
- 2022-02-22
Good Laboratory Practice (GLP)
Toxikon Corporation/Labcorp Bedford LLC
- 2020-05-05
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
University of Kentucky
- 2020-04-07
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Steiner Biotechnology, LLC
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Evidentiary Expectations for 510(k) Implant Devices: Draft Guidance for Industry and Food and Drug Administration Staff (Status: Draft)
- Redbook 2000: IV.C.9.b. Guidelines for Developmental Toxicity Studies (Status: Final)
- Redbook 2000: IV.C.9.a.Guidelines for Reproduction Studies (Status: Final)
- Redbook 2000: IV.C.5.b. One-Year Toxicity Studies with Non-Rodents (Status: Final)
- Redbook 2000: IV.C.4.b. Subchronic Toxicity Studies with Non-Rodents (Status: Final)
- Redbook 2000: IV.C.4.a. Subchronic Toxicity Studies with Rodents (Status: Final)
- Redbook 2000: IV.C.3.b. Short-Term Toxicity Studies with Non-Rodents (Status: Final)
- Redbook 2000: IV.C.3.a. Short-Term Toxicity Studies with Rodents (Status: Final)