On September 17, 2026, FDA’s Center for Veterinary Medicine (CVM) published Draft Guidance for Industry (GFI) #298 on Target Animal Safety Evaluation for Veterinary Monoclonal Antibody Products (VICH GL62) (Guidance). The Guidance provides harmonized international recommendations for the target animal safety (TAS) evaluation supporting approval of veterinary monoclonal antibody products (VMAPs). It was developed through the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) and is intended to promote a consistent scientific approach to evaluating VMAP TAS across VICH regions.
VICH member regions require applicants to submit TAS data for the approval of veterinary medicinal products, including VMAPs. The Guidance explains that VMAPs present risks and safety questions that differ from those associated with traditional small-molecule drugs: “[t]he VICH [guidances] available for TAS (i.e., VICH GL43 for pharmaceutical products and VICH GL44 [for veterinary live and inactivated vaccines]) do not fully address the TAS evaluation for a VMAP.” The Guidance outlines scientific principles specifically tailored to VMAPs that are intended to “be used in conjunction with VICH GL43,” implemented by CVM as GFI #185, which is the general TAS framework for veterinary pharmaceutical products.
The Guidance recommends that applicants perform a Comprehensive Risk Assessment (CRA) as the organizing framework for the TAS evaluation, to be “used to determine the extent of data needed to support the overall TAS evaluation of the VMAP in the target animal.” The CRA should consider a variety of factors, including the proposed indication; treatment duration; dose, route, and formulation; monoclonal antibody attributes such as immunoglobulin class, degree of speciation, and directed or functional mutations; target specificity and cross-reactivity; pharmacokinetics (PK); pharmacodynamics (PD) and biological activity, including whether the effect is agonistic or antagonistic; immunogenicity, immunotoxicity, and immunomodulation risks; potential transplacental or transmammary transfer; target biology and expression in healthy and diseased animals; and knowledge about similar monoclonal antibodies in both humans and animals. The CRA may draw on literature, explanations of molecular engineering, binding data, in silico analyses, and exploratory in vivo studies.
TAS studies for VMAPs should be designed using the principles of VICH GL43 but with VMAP-specific considerations. The Guidance explains that the margin-of-safety (MOS) “study design, as described in VICH GL43, may be adapted or extended to ensure evaluation of potentially significant safety risks specific to each VMAP.” In some cases, a “VICH GL43 MOS Study may not be necessary if an adequate TAS evaluation can be obtained from other studies, including field studies,” while “[i]n other cases, it may be necessary to conduct more than a MOS study to ensure proper evaluation of all significant TAS risks.”
- Study Objectives and Endpoints. The overall objectives, methods, and endpoints for VMAP TAS evaluations should be established based on conclusions from the CRA.
- Selection of Study Animals. TAS studies for a VMAP should be conducted in the target species. Laboratory studies should be conducted in healthy animals, and field studies should be conducted in animals in the intended target population (i.e., animals with comorbidities, concurrent treatments, or individual genetic backgrounds).
- Route of Administration and Dose. TAS studies should use the proposed route of administration and dosing regimen, with dose selection tailored to the VMAP’s pharmacology and toxicology. The Guidance states: “The minimum ‘1X’ dose level used in laboratory TAS studies should be based on the highest dose exposure from the intended label dose.” It emphasizes that overdose studies remain important and notes that overdose testing should be performed “to evaluate for increased tissue penetration, potential for binding to unexpected homologous epitopes, and other objectives related to evaluating the safety profile.”
- Product Used in Studies. TAS studies should use the final formulation of the drug product. If a non-final formulation is used, sponsors should provide a scientific justification and demonstrate that the study results can be reliably extrapolated to the final marketed product.
- Biological Activity (Pharmacodynamics). The TAS evaluation should be based on a CRA that considers “the direct effects of the VMAP and the potential for unintended on-target effects, off-target effects, and effects on the immune system.” Safety evaluations should be informed by the VMAP’s mechanism of action, target biology, and available pharmacology data.
- Pharmacokinetics. The Guidance recommends characterizing the PK profile of VMAPs to support the establishment of a safety profile.
- Immunogenicity. The Guidance states that the application should include “an Immunogenicity Risk Assessment where appropriate” and that “[t]he risk of immunogenicity for each VMAP should be assessed on an individual basis.”
- Additional Safety Evaluations. The Guidance addresses several additional considerations for the TAS evaluation, each adapted from the corresponding sections of VICH GL43.
- Applicants should conduct reproductive and developmental safety evaluations if the intended target population includes breeding, pregnant, or lactating animals, “unless an acceptable scientific justification for the absence of risk can be presented.” If relevant data are not available and justification cannot be provided, “the product label should state that safety has not been determined in breeding, pregnant, or lactating animals, or their offspring.”
- Mammary gland studies should be used to evaluate the safety of VMAPs intended for intramammary use in lactating or non-lactating animals.
- Applicants should use local tolerance studies to evaluate local effects at the site of administration and include evaluation of the administration site in both laboratory and field studies.
- Other Considerations. The Guidance explains that general toxicity studies using non-target species are not needed as preliminary data for VMAPs, genotoxicity is not expected to be a concern for VMAPs unless the CRA identifies a basis for evaluation, and carcinogenicity assessment is warranted only when the CRA identifies a specific concern.
FDA requests that interested parties submit comments on the Guidance by November 17, 2026.
If you have any questions concerning the material discussed in this client alert, please contact the members of our Animal Food and Drug practice.
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