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CVM GFI #278 Human User Safety in New and Abbreviated New Animal Drug Applications

FinalCenter for Veterinary Medicine06/21/2024
Human User SafetyRisk CharacterizationTarget Animal Safety

Description

Human User Safety (HUS) is an integral component of the overall safety evaluation of proposed new animal drugs. The FD&C Act does not provide specific guidance on data requirements or assessment methods to identify the risks or the risk mitigation measures for human users of new animal drugs. This guidance clarifies the current approaches and recommendations for HUS assessment and submission of HUS information to support the overall safety of proposed new animal drugs prior to approval.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

10
Animal Cells, Tissues, and Cell- and Tissue-Based Products

ACTP products mentioned in abbreviations.

Type C medicated feed

Final medicated feed intended for consumption; Medicated feed intended for consumption as a complete feed; medicated feed intended for direct consumption by animals; Medicated feed intended for direct consumption by animals

Type B medicated feed

intermediate medicated feed; A medicated feed intended for further manufacture of another medicated feed.; Intermediate medicated feed; Intermediate medicated feed product; medicated feed intended for further mixing; Intermediate medicated feed used to manufacture Type C feed

Intentional Genomic Alteration

IGA products mentioned in abbreviations.

Oncology Drugs for Use in Animals

Specific category requiring HUS considerations.

Protein-based drug products

Specific category requiring HUS considerations.

New Animal Drug

The category of products covered by this guidance.

Generic New Animal Drug

typically do not present novel HUS considerations

Abbreviated New Animal Drug

Human User Safety in New and Abbreviated New Animal Drug Applications

Type A medicated article

used to manufacture medicated feed; A concentrated form of a drug used to manufacture medicated feed.; Concentrated drug form used to manufacture medicated feed; single ingredient component for medicated feed; Medicated feed mill license is required to manufacture a Type B or Type C medicated feed from a Category II, Type A medicated article.; Concentrated drug form for manufacturing medicated feed; Concentrated form of animal drug used to manufacture medicated feed; Type A medicated articles fo

Stakeholders

4
Sponsor

Entity responsible for submitting applications under section 524B

Veterinary health professionals

Intended audience for understanding HUS principles.

Human User

any person who may come into contact with the new animal drug

Drug Sponsor

entity responsible for evaluating HUS throughout the drug lifecycle

Regulatory Context

Regulatory Activities

4
NADA

New animal drug applications; New Animal Drug Application

ANADA

Abbreviated new animal drug applications

INAD

Investigational New Animal Drug file

JINAD

Generic Investigational New Animal Drug file

Document Types

8
Safety Data Sheet

SDS used as a source of safety information.

SDS

Safety Data Sheet for the product

FOI summary document

Freedom of Information summary for approved drugs

package insert

User Safety Warnings section of the package insert

Blue Bird label

Representative labeling for Type B and Type C medicated feeds

Client information sheet

Specific labeling element used as a mitigation strategy.

Safety Data Sheets

SDS may provide information on the physical properties of chemical components.

Labeling

Cybersecurity information should be included in device labeling

Attributes

6
No-Observed-Adverse-Effect Level

toxicology endpoint for starting dose

PPE

Personal Protective Equipment recommended for use

Seclusion time

Time the animal should be secluded without human contact to mitigate exposure.

Chronic exposure

Chronic exposures are generally considered to be those where there are multiple exposures events over 91 days

Acute exposure

Acute exposures are generally considered to be single exposures

Toxicity Profile

factor influencing HUS assessment

Technical Details

Substances

3
Active Pharmaceutical Ingredient

examples of such components include but are not limited to the active moiety (API)

Animal drug protein

If the animal drug protein is highly homologous to a human protein, it may cross-react.

Controlled Substances

active substances regulated by the DEA

Testing Methods

6
Dislodgeable residue studies

exposure studies conducted with the drug product, such as dislodgeable residue studies

Human factor studies

Conducted with representative users to assess the adequacy of the product-user interface design.

Dislodgeable residue study

Type of post-administration study recommended for topical products.

Field studies

Studies conducted in the target animal species to demonstrate effectiveness and safety.

Target animal safety studies

Studies conducted in the target animal species to provide information on the safety of an investigational product.

Toxicity studies

Studies conducted in vivo or in vitro to assess hazards associated with exposure to an animal drug.

Processes

2
Risk Characterization

estimating the risk to the human user using hazard and exposure

gene therapy

products necessitating special disposal procedures

Clinical Concepts

2
Anaphylactoid reactions

Examples of adverse immune system responses subsequent to accidental exposure.

adverse drug experiences

reporting suspected adverse events

Identified Hazards

Hazards

3
Foreseeable Accidents

exposure outside the scope of labeled instructions like spills or self-injection

Antimicrobial resistance

substances that may contribute to antimicrobial resistance

Viral shedding

Potential risk associated with viral vectors

Standards & References

Specifications

2
No-Observed-Adverse-Effect Level

The highest dose that did not elicit an adverse effect in a toxicological study

Margin of Exposure

calculation of the margin of exposure (MOE)

Related CFR Sections (3)

See Also (8)

CVM GFI #278 Human User Safety in New and Abbreviated New Animal Drug Applications | Guideline Explorer | BioRegHub