Drugs

Comments on FDA Revised Immunotoxic Potential Guidance

David McFarland

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The Physicians Committee for Responsible Medicine (PCRM) says it welcomes FDA support for replacing and reducing animal use in testing and encouraging sponsors to consult with reviewers when considering a non-animal testing method. In a comment on an agency revised draft guidance on nonclinical safety evaluation of the immunotoxic potential of drugs and biologics, PCRM recommends that the agency clearly state its preference for new approach methodologies to evaluate sensitizing potential and direct sponsors to justify any use of in vivo methods. The group also recommends that FDA: 

  •          state when studies evaluating skin sensitization are or are not recommended and the agency’s preference for in chemico and in vitro methods;
  •          refer to nonanimal testing methods as alternatives to the T-cell-dependent antibody response assay that sponsors should consider if the weight of evidence suggests potential immunotoxicity; and
  •          state that nonhuman primate enhanced pre- and postnatal development studies can be waived when the weight-of-evidence suggests that there will be an adverse effect on pregnancy outcome and that any planned studies be deferred until the time of marketing.

A comment letter from Charles River Laboratories says the FDA revised draft is a useful accompaniment to the ICH S8/6 guideline with a focus on immunomodulators and covers both biologicals and small molecules. It says there are places in the FDA guidance where further discussion or clarification would add clarity due to the complexity of the immune system and the potential outcomes.

A Biotechnology Innovation Organization letter says that several existing guidance documents address, to variable extents, nonclinical immune system safety assessments. “While the stated purpose of this guidance is to supplement the recommendation provided in the existing guidances … the language and organization of the proposed draft guidance lacks clarity and/or appears to conflict with existing guidance. In the current form, we are concerned that the draft guidance will mislead some sponsors, particularly those who do not have immunotoxicity expertise, and lead to either inadequate safety packages or unnecessary animal studies.” The association also provides specific line-by-line comments.

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