Passage of Senate Bill S. 5002, “FDA Modernization Act 2.0”, relating to animal testing

On Thursday, September 29, 2022, Senate Bill 5002, “FDA Modernization Act 2.0,” was introduced in the Senate and passed unanimously. Article 2 of the bill is entitled “Alternatives to animal testing”. The bill incorporates language based on provisions incorporated into the House of Representatives FDA User Fee Reauthorization Bill for Human Drugs (HR 7667) as well as language from the bill Separate Senate 4288 “Animal Testing Reduction Act,” introduced in the spring, which would change the animal testing provisions for human biological products, such as vaccines and blood-derived products. Senate Bill 5002 does not apply to drugs or biologics for animals. The bill has been sent to the House of Representatives.

Senate Bill 5002 would amend Section 505(i) of the Federal Food, Drug, and Cosmetic Act (FDCA) (21 USC § 355(i)) to:

  • Replace the term “non-clinical trials” with the current “pre-existing clinical trials (including animal testing)” in paragraph (1)(A) and the current “animal” in paragraph (2)(B); and
  • Add a new section 505(z) (21 USC 355(z)) defining “non-clinical testing” as:

a test performed in vitro, in silico or in chemico, or a non-human in vivo test that takes place before or during the clinical trial phase of the investigation of the safety and efficacy of a drug, and may include animal testing, or non-animal or human biology-based testing methods, such as cell-based assays, microphysiological systems, or bioprinted or computational models.

The Act would also amend Section 351(k)(2)(A)(i)(I)(bb) of the Public Health Services Act (42 USC § 262(k)(2)(A)(i). )(I )(bb)) to replace “an assessment of toxicity (which may be based on, or consist of, one or more studies described in (aa) or (cc)” for the current “animal studies (including including toxicity assessment).”

Section 505 of the FDCA applies to the approval and regulation of drugs for human use. The changes to Section 505 would not eliminate the use of animal testing in approving human drugs, but would allow for other types of testing or analysis. Section 505(i)(1)(A) currently states that the Secretary of HHS may issue regulations governing the investigation of the safety and effectiveness of human drugs through “preclinical testing (including animal testing)” that are sufficient to warrant clinical trials of the drug. The law would allow the justification to be based on non-animal testing or analysis, but animal testing could still be used for this purpose. Similarly, Section 505(i)(2)(B) provides that clinical investigations may begin after the submission of “adequate information about the chemistry and manufacturing of the drug, the controls available for the drug, and the tabulations of data primaries from animal and human studies. “The law would provide for other types of tests or analyzes on which tabulations of primary data could be based.

The effect of changes to the Public Health Services Act (PHSA), which is limited to biosimilars, is to remove the requirement for animal testing. Section 351(k)(2)(A)(i)(I)(bb) of the PHSA currently provides that a biosimilar product application must include information demonstrating that the biologic product is biosimilar to the reference product on the database derived from “animal studies (including toxicity assessment)”, unless the FDA deems such information unnecessary. Review of this section would generally continue to require a toxicity assessment, but this assessment could be based on the tests described in subparagraph aa: “analytical studies which demonstrate that the biological product is very similar to the reference product despite differences in clinically inactive components”, or subparagraph cc: “one or more clinical studies (including evaluation of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity and potency under one or more appropriate conditions of use for which the reference product is registered and intended to be used and for which registration is sought for the biological product. As it does now, the FDA would, of course, determine whether such studies were appropriate in a given case. The same goes for animal studies, which we note the bill does not prohibit.

Norman D. Briggs