Фармацевтические ассоциации призывают FDA сохранить гибкость в использовании тестов на животных при разработке онкопрепаратов

Drug, regulatory, and laboratory animal testing groups want the US Food and Drug Administration (FDA) to ensure flexibility in choosing when to rely on animal testing and when other forms of data may be sufficient for cancer drug safety studies. In June, FDA proposed a guidance to reduce the need for animal testing in the development of oncology drugs as part of its broader efforts to reduce animal testing in drug development. The agency emphasized that, by using the risk-based assessment approach outlined in the guidance, it anticipates streamlining the oncology drug development process without compromising patient safety. (RELATED: FDA oncology draft guidance aims to reduce animal testing, Regulatory Focus 1 June 2026) Drug lobby group PhRMA emphasized that while it supports FDA's efforts to reduce the need for animal testing through the guidance, its success will depend on ensuring flexibility with existing guidances and related International Council for Harmonisation (ICH) guidelines, providing sponsors with regulatory predictability, and ensuring regulatory implementation across the agency's review divisions. FDA includes several situations in Section III.A of the proposed guidance on how researchers may obtain toxicology data that relies less on animal studies. PhRMA asked FDA to confirm that the product classes referenced in that section reflect the most common use cases but are not exhaustive of the circumstances covered by the guidance. The group said it would avoid limiting researchers, provide flexibility, and prevent the discouragement of innovative approaches. PhRMA asked FDA to harmonize its guidance with ICH on applying weight of evidence (WoE) framework for nonclinical assessments. The group noted that WoE may be applicable to pharmacology, pharmacokinetics, and toxicology, and that international harmonization of its use would help sponsors meet requirements across multiple regulatory jurisdictions. PhRMA also noted that while Section III.B includes information on what the agency expects to see in WoE risk assessments, it doesn’t provide detail on how regulators intend to weigh such information to determine if the assessments are sufficient. "Given that the streamlined framework described in the Draft Guidance relies on sponsors applying a WoE approach to nonclinical assessment, sponsors would benefit from further clarity around how FDA will consider these elements to inform planning nonclinical programs years in advance of a regulatory interaction,” said the group. "PhRMA requests that FDA explicitly state that WoE risk assessments referenced in the Draft Guidance are not limited to the four enumerated elements (nonclinical/clinical data on the investigational product; literature-based assessment of potential toxicities; toxicity findings in animals and humans; 'other data' including fit-for-purpose NAMs), and that other approaches leveraging the sponsor’s legacy toxicology study data may be used with appropriate justification." While the guidance asks sponsors to discuss alternative approaches to those laid out in the document early in their product development through formal meetings with the agency, PhRMA noted that nonclinical program designs are typically drafted years before clinical development milestones are met and are difficult to revise once an investigational drug is under study. The group said that timely and substantive feedback from the agency is critical for sponsors considering alternative nonclinical program designs. "Consistent with PhRMA’s previous recommendation in comments on the Monoclonal Antibodies: Streamlined Nonclinical Safety Studies draft guidance, we request that FDA clarify that requests to discuss proposed WoE-based alternative approaches under this guidance are an appropriate topic for INTERACT meetings, early Type B (pre-IND) meetings, and Type D meetings," said PhRMA. "We believe that providing clear, accessible channels for early feedback on WoE-based approaches will be critical to realizing the intended benefits of the Draft Guidance." The Critical Path Institute (C-Path) also asked FDA to be flexible across therapeutic areas and product types while emphasizing the need to justify decisions within scientific contexts. It encouraged broad stakeholder collaboration to advance and accept novel drug development tools and to strengthen regulatory decision-making. C-Path noted that the guidance title uses the term 'conjugated products' without clearly defining the term. Based on the document's toxicology section, the group said it appears the agency is specifically addressing antibody-drug conjugates (ADCs) with cytotoxic payloads. However, C-Path said it isn't clear whether the agency is referring to peptide-drug conjugates, non-cytotoxic small-molecule conjugates, or Fc-fusion conjugates, and asked regulators to define the term and specify which types of conjugate products fall within the scope of the guidance. C-Path also asked FDA to strengthen its position on how new approach methodologies (NAM) may be used in the guidance by rephrasing that WoE risk assessments may include fit-for-purpose NAMs and other appropriate data. It also asked that the agency recognize NAMs qualified or endorsed by other consortia. "The document would benefit from a stronger statement on the utility of NAMs," said C-Path. "The draft guidance General Considerations for the Use of New Approach Methodologies in Drug Development has some useful considerations for validating NAMs for fit-for-purpose validation. "The WoE risk assessment section does not state whether NAMs that have been qualified, validated, or endorsed through recognized external consortium (i.e., C-Path’s NAMs Developer Coalition) would have weight in a WoE submission, or whether every sponsor must independently justify a NAM's fitness for purpose regardless of prior external validation," the group added. C-Path said it's not clear what a fit-for-purpose NAM is in the context of a toxicity WoE assessment for an oncology biologic or conjugate, as set out in the guidance, and asked the agency to provide context-of-use criteria. Some of the context-of-use that the group proposed the agency include in the guidance are NAMs that are biologically relevant to the human toxicity or pharmacological mechanism being evaluated, acceptable technical performance, and predictive value. EMD Serrano, a subsidiary of German drugmaker Merck KGaA, said it supports FDA's effort to reduce reliance on animal testing in developing oncology drugs, noting a growing scientific consensus that, in certain circumstances, well-designed, data-informed risk assessments can achieve the same goals without compromising patient safety. It also noted its agreement with the agency's view that, in certain circumstances, WoE risk assessment may be used instead of 3-month toxicology studies. EMD Serrano said the guidance should emphasize early on that relying on WoE approaches and integrating human-relevant models into nonclinical safety assessments may increase the likelihood of translating the data for human use. The company also noted that the guidance states that animal toxicology studies should use pharmacologically relevant species and pharmacology studies should demonstrate binding of the oncology pharmaceuticals to molecular targets and elicit the intended pharmacologic effects but doesn’t provide any additional details on the acceptance criteria for what is considered sufficient binding affinity or what pharmacologic activity qualifies a species as relevant. The company asked FDA to clarify the acceptance criteria or provide a decision tree to help species selection for monospecific and multispecific biologics. The draft guidance states that in situations where the payload safety of the antibody-drug conjugates with cytotoxic payloads is well-characterized and is the main driver of toxicities, FDA expects a 3-month toxicology study in rodents only, regardless of whether there is ADC binding to the target antigen. EMD Serrano asked the agency to clarify its justification for the position. "Greater transparency on the scientific basis for this requirement would benefit sponsors in their development planning. Furthermore, the guidance does not address novel linker chemistries, which can significantly alter payload release kinetics and off-target toxicity profiles," said EMD Serano. "As a result, it remains unclear which ADC formats are eligible for the rodent-only 3-month study paradigm. "We therefore encourage the Agency to clarify whether and how novel or non-standard linker technologies affect eligibility for this streamlined approach, and to consider including representative examples of ADC formats that would or would not qualify," the company added. EMD Serrano also said it would also be useful to include an appendix or section in the guidance that includes examples or case studies of acceptable WoE submissions. The American College of Laboratory Animal Medicine (ACLAM) said it agrees with FDA's recommendation to streamline or replace 3-month general toxicology studies. The group recommended several changes to the guidance, including asking the agency to allow flexibility in requiring additional animal studies, such as nonhuman primate (NHP) studies, in situations of scientific uncertainty for novel drugs. It also asked the agency to clarify the terms "well-characterized" and “loss of exposure” in the context of WoE risk assessments so that they are applied consistently across review divisions and echoed other commenters that the guidance should be harmonized with international standards. "ACLAM supports that the draft guidance correctly frames NAMs as an optional supplement to WoE ('could be supplemented with new approach methodologies (NAMs), as appropriate') rather than as standalone replacements," said ACLAM. "ACLAM encourages the Agency to articulate a clear pathway for prospective NAM qualification against human outcomes, within a defined context of use, so their role may responsibly expand over time. "ACLAM further urges that the responsible adoption of NAMs be tempered by a realistic appraisal of their current state of readiness, distinguishing genuine, data-supported utility from the claims that exceed the available qualification data," the group added. "Accordingly, ACLAM recommends that any expanded reliance on NAMs be governed by clearly defined qualification criteria—context of use, human biological relevance, technical characterization, and fit-for-purpose adequacy—so that such methods are deployed only where their validation status genuinely supports the safety decision at hand, with animal studies remaining essential wherever residual scientific uncertainty could place early-phase patients at risk."