Stakeholders want clearer terms in FDA's generally accepted scientific knowledge guidance

Drugmakers and research groups are generally supportive of the US Food and Drug Administration’s plan to allow greater flexibility in using generally accepted scientific knowledge (GASK) as part of regulatory applications. However, in comments on the recent draft guidance, stakeholders asked for a clearer definition of GASK and more examples of how it could be used, with one group pushing back on the idea of having GASK take the place of certain nonclinical testing.

In May 2023, the FDA released draft guidance outlining when it may be appropriate to use GASK to meet the nonclinical safety requirements of new drug applications (NDAs) and biologics license applications (BLAs) instead of, or in addition to, newly conducted nonclinical studies. (RELATED: FDA drafts guidance on using ‘generally accepted’ knowledge to support drug approvals, Regulatory Focus 24 May 2023)

Seeking clearer definition

The Pharmaceutical Research and Manufacturers of America (PhRMA) told FDA it supports the principle of relying on GASK in some cases. However, PhRMA commented that more information is needed on how the FDA defines GASK, specifically when information would be considered “non-product specific.” PhRMA also cautioned that GASK should not be defined in a way that allows sponsors to skirt patent certification requirements.

“PhRMA believes that appropriately defining what constitutes GASK is critical to ensuring that the GASK concept can be used to avoid conducting unnecessary studies but not be used as an end-run around intellectual property protections and the existing legal and regulatory framework intended to facilitate innovation,” the group wrote.

PhRMA asked FDA to clarify that the guidance does not create a new abbreviated pathway for biologics that does not meet the criteria under section 351(k) of the Public Health Service Act for biosimilar or interchangeable BLAs. Additionally, they urged the agency to better define GASK and specify that it does not include information generated about a specific product or class of products, that it may not be based on non-product-specific published literature that references product-specific published literature, and that the submitting sponsors must demonstrate that information is GASK and not based on an assertion by the applicant or an expert.

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) commented that the draft guidance supports the concept of “3R-based animal usage” in nonclinical drug development, which is focused on replacement, reduction, and refinement to minimize animal usage in research. The group asked the FDA to provide some additional examples of scenarios where GASK could be used in answering questions related to pharmacology, [drug metabolism and pharmacokinetics] DMPK, and toxicology, as well as the use of GASK related to an altered biological mechanism or pathway.

The Physicians Committee for Responsible Medicine also supported the greater reliance on GASK to reduce animal use. “As our analyses of animal use in nonclinical studies submitted in drug applications demonstrate, animal use could be reduced dramatically by avoiding nonclinical studies that do not add value to FDA’s evaluation. To maximize the use of GASK, we urge FDA to provide more comprehensive examples of its application in different contexts and to communicate these recommendations to sponsors effectively,” the Physicians Committee commented.

GASK as supporting data only

The National Center for Health Research commented that it supports the agency’s efforts to “remain flexible” but urged officials not to use GASK as the sole source of nonclinical data in NDAs or BLAs. “Instead, GASK should only be used to support sponsor data and should not replace the vital research that is needed to create a robust safety and efficacious drug profile,” the group wrote.

The National Center for Health Research asked FDA to revise the guidance, noting that even when a drug’s mechanism of action or biologic pathway is well understood, the drug should still be tested to ensure there are “no downstream or unanticipated effects when in vitro.”

Public comments on GASK draft guidance

Stakeholders want clearer terms in FDA's generally accepted scientific knowledge guidance

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