CVM GFI #185 (VICH GL43) Target Animal Safety for Veterinary Pharmaceutical Products | Guideline Explorer

Description

Data from target animal safety (TAS) studies are required for registration of veterinary products in the regions participating in the VICH. International harmonization of standards for essential TAS studies will facilitate adequacy of data and minimize the need to perform separate studies for regulatory authorities of different countries. Appropriate international standards should reduce research and development costs by minimizing repetition of similar studies in each region. Animal welfare should benefit because fewer animals may be needed. This VICH TAS guidance has been developed as a harmonized standard to aid in development of mutually acceptable TAS studies for relevant governmental regulatory bodies.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

2

Investigational Veterinary Pharmaceutical Product

Subject of target animal safety evaluation; Pharmaceutical form being evaluated in clinical or non-clinical studies

IVPP

Investigational Veterinary Pharmaceutical Product

Stakeholders

1

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

3

Registration

Requirement for facilities to register under section 415 of the FD&C Act

Field studies

Studies intended to evaluate effectiveness and provide TAS data under intended use

Reproductive safety studies

Required for systemically absorbed API in breeding animals

Document Types

4

Study protocol

Should include biological rationale for subgroups

Labeling

Cybersecurity information should be included in device labeling

Proposed labeling

Dosing should follow the use conditions suggested in the label

Study Report

Accompanying report that must be traceable back to original data

Attributes

4

Margin of Safety

calculated using the formula Acceptable exposure level / Potential patient exposure

Pharmacokinetic profiles

Comparison between laboratory animals and target species

Bioequivalence

Risk factor to be assessed during manufacturing changes

No-observable-adverse-effect level

NOAEL determined by microscopy

Technical Details

Substances

2

Active Pharmaceutical Ingredient

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

API

Active Pharmaceutical Ingredient

Testing Methods

7

Clinical Pathology Tests

Includes hematology, blood chemistry, and urinalysis; Includes hematology, blood chemistry, urinalysis, fecal analysis; Specific evaluation of potential adverse effects in field studies

Necropsy

Procedure for D. immitis worm counts

Histopathology

The standard of truth for measuring diagnostic performance.; Typically used as a truth standard for optical imaging drugs.

Hematology

Clinical data required for safety evaluation

Blood Chemistry

Analysis of electrolytes, proteins, and enzymes

Urinalysis

Clinical data required for safety evaluation; Safety assessment parameter (UA)

Descriptive statistical methods

Used for safety data summarization

Processes

7

Mammary gland safety studies

Evaluation of IVPPs intended for intramammary use

Margin of Safety Studies

Studies to provide information on the safety of an IVPP in the intended species

Reproductive Safety Studies

Specialized laboratory safety study design; Studies conducted to evaluate effects on estrous cycle, mating, and offspring

Injection Site Safety Studies

Evaluation of local tolerance at the site of administration

Margin of safety study

Includes multiples of the highest intended drug dosage to demonstrate safety margin.

Necropsy

Procedure where worms are identified and counted for effectiveness calculations.

Histopathology

General requirements including written SOPs

Clinical Concepts

5

Adverse Events

Reporting adverse events when engaging with patients.; changes may be related to benefits, tolerability, and/or unintended effects

Teratogenicity

Developmental toxicity finding

Adverse Event

Reactions or events observed in patients; Information described in an ICSR; Information associated with the use of biopharmaceuticals; Clinical information corrected during an amendment; Section D describes the singular subject who experienced one or several adverse events/reactions.; Reactions or events observed in patients or foetuses; The onset of a reaction/event following drug administration.; Reporting of reactions to suspect drugs; Reaction or event reported by the primary source; Reactio

Adverse effects

Reported outcomes following the use of a drug or drug class.; provide information to predict potential adverse effects in the target species

Spermatogenesis

the process of sperm production in males

Identified Hazards

Hazards

2

Systemic clinical signs

Abnormal findings requiring gross examination

Acute inflammatory effects

Safety concern evaluated in mammary gland studies

Standards & References

Specifications

1

Somatic cell count

Quantitative variable for mammary gland safety assessment

Related CFR Sections (2)

21CFR514.1§ 514.1 Applications.
(a) Applications to be filed under section 512(b) of the act shall be submitted in the form and contain the information described in paragraph (b) of this section, as appropriate to support the particular submission. If any part of the application is in a foreign language, an accurate and complete ERead full regulation →
21CFR510.3§ 510.3 Definitions and interpretations.
As used in this part:Read full regulation →

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Quality control unit failed to exercise its responsibility

101

Failure to conduct at least one test to verify the identity of each component

95

Failure to establish adequate written procedures for production and process control

88

Failure to thoroughly investigate any unexplained discrepancy or failure of a batch

56

Failure to have appropriate laboratory determination of satisfactory conformance to final specifications

56

Failure to establish an adequate quality control unit

49

Failure to test samples of each component for identity and conformity

47

Failure to establish laboratory controls

35

Failure to thoroughly investigate any unexplained discrepancy

28

Failure to test samples of each component for identity

25

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics