USFDA Draft Guidance: Oncology Pharmaceuticals: Streamlined Nonclinical Safety Studies for Biologics and Conjugated Products

In May 2026, the FDA Oncology Center of Excellence (OCE) and Center for Drug Evaluation and Research (CDER) issued the draft guidance Oncology Pharmaceuticals: Streamlined Nonclinical Safety Studies for Biologics and Conjugated Products. The guidance introduces risk-based approaches for nonclinical safety assessments of certain oncology biologics and conjugated products, aiming to facilitate development while maintaining patient safety.

The guidance highlights that data analyses, regulatory experience with biologics, antibody-drug conjugates (ADCs), and CD3 bispecific constructs, as well as lessons learned from efforts to reduce non-human primate use, have contributed to the development of these recommendations.

The FDA emphasizes that these approaches are intended to improve development efficiency without compromising the protection of patients participating in clinical trials or receiving approved therapies.

Scope

The guidance applies to certain oncology biologics and conjugated products, with particular focus on:

• Monoclonal antibodies

• PD-(L)1 blocking antibodies

• CD3 bispecific T-cell engagers

• Antibody-drug conjugates (ADCs)

• Other biologic oncology products

The recommendations primarily address general toxicology studies, especially 3-month toxicology studies that are commonly used to support clinical development and marketing applications.

The guidance does not address nonclinical assessments related to impurities or excipients.

Streamlining General Toxicology Studies

One of the key messages of the guidance is that traditional toxicology programmes can often be streamlined when sufficient scientific understanding of the product, target biology, and toxicity profile already exists.

The FDA encourages sponsors to consider alternative approaches that reduce animal use while still adequately assessing safety risks. In some situations, a 3-month toxicology study may be replaced or supplemented by a structured risk assessment based on available evidence.

The guidance also suggests that sponsors may consider conducting a 3-month toxicology study early in development rather than performing separate 1-month and 3-month studies, thereby reducing overall animal usage.

Pharmacologically Relevant Species

For biologics, toxicology studies should be conducted using pharmacologically relevant species. Sponsors should demonstrate that the selected animal species expresses the molecular target and exhibits the intended pharmacological response.

When no pharmacologically relevant species can be identified, the FDA states that safety assessments may instead rely on a Weight of Evidence (WoE) Risk Assessment rather than animal toxicology studies.

This approach recognises the limitations of traditional animal testing for certain highly targeted biologics.

Recommendations for Specific Product Classes

Biologics

For biologics that demonstrate similar pharmacological activity in both rodents and non-rodents, the FDA indicates that general toxicology studies may be conducted in a single rodent species and supplemented with a Weight of Evidence assessment where appropriate.

This approach can significantly reduce the number of animals required without compromising the quality of safety evaluations.

PD-(L)1 Blocking Antibodies

For PD-(L)1 blocking monoclonal antibodies, the FDA notes that chronic safety assessments may be supported through a Weight of Evidence Risk Assessment instead of a dedicated 3-month toxicology study.

In certain circumstances, sponsors may also justify the use of non-sacrificial 1-month toxicology studies combined with a risk-based assessment strategy.

CD3 Bispecific T-Cell Engagers

For CD3 bispecific T-cell engagers, the guidance explains that chronic safety evaluations may similarly rely on a Weight of Evidence Risk Assessment rather than conducting a separate 3-month toxicology study.

This recommendation reflects the extensive scientific and regulatory experience accumulated with this class of products.

Antibody-Drug Conjugates (ADCs)

For ADCs containing well-characterised cytotoxic payloads, the FDA indicates that 3-month toxicology studies may be conducted in rodents only when the payload is the primary driver of toxicity.

Where the antibody target is novel and not present in rodents, sponsors should supplement toxicology data with an appropriate Weight of Evidence assessment to address target-related safety concerns.

Weight of Evidence (WoE) Risk Assessment

A central feature of the guidance is the introduction of the Weight of Evidence Risk Assessment as an alternative or supplement to traditional animal studies.

The FDA explains that a WoE assessment may integrate multiple sources of information, including:

• Nonclinical pharmacology data

• Pharmacokinetic information

• Existing clinical experience

• Published literature

• Known target biology

• Class-related toxicity information

• New Approach Methodologies (NAMs)

This integrated approach allows sponsors to evaluate safety risks using the totality of available evidence rather than relying exclusively on animal testing.

New Approach Methodologies (NAMs)

The guidance also recognises the growing role of New Approach Methodologies (NAMs) in modern drug development. NAMs may include innovative laboratory, computational, or in vitro approaches that contribute additional information for risk assessment.

The FDA notes that NAMs can be incorporated into Weight of Evidence assessments where scientifically appropriate and adequately validated.

This reflects broader regulatory efforts to advance alternative methods that improve efficiency while reducing animal use.

References

Oncology Pharmaceuticals: Streamlined Nonclinical Safety Studies for Biologics and Conjugated Products – FDA Draft Guidance