FDA drafts guidance on using ‘generally accepted’ knowledge to support drug approvals

The US Food and Drug Administration (FDA) on Wednesday issued draft guidance offering examples of how drug sponsors can rely on generally accepted scientific knowledge (GASK) in place of or to supplement certain nonclinical safety data, which could save companies and the agency time and resources.

FDA said it has received an increasing number of questions from industry about when they can use GASK in their new drug applications (NDAs) and biological license applications (BLAs), which prompted the agency to develop the guidance.

FDA explains that while standalone NDAs and BLAs must include data that demonstrates the safety and effectiveness of a drug or the safety, purity and potency of a biological product, that information does not always have to come from studies conducted by the sponsor. Sponsors may also cite studies for which they have the right of reference or information that is considered GASK. FDA notes that this is also true for 505(b)(2) NDAs and biosimilars submitted under section 351(k) of the Public Health Service Act.

“In some cases, however, what is already known, for example, about a drug, the patient’s condition, or a relevant biological process (i.e., the biological context in which a drug is expected to act) in a given patient population is sufficient to confidently predict the outcome of a given nonclinical study,” said the agency. “If there is GASK relevant to the application, it may be unnecessary for a sponsor to conduct certain nonclinical studies.”

“This may result in streamlined product development that avoids unnecessary animal testing, decreases a drug’s development costs, and quickens the drug’s time to approval and marketing — and thus, its availability to patients,” FDA added.

As part of their application, sponsors need to submit nonclinical information such as the pharmacology, disposition, and toxicology of the drug that reviewers can use to understand what affect the drug will have on the patient. However, sometimes that information may be GASK, in which case the sponsor could just provide relevant GASK rather than conduct a nonclinical study.

The guidance includes two examples where sponsors could fulfill certain nonclinical safety requirements by referencing GASK information in lieu of conducting nonclinical studies.

The first example is a scenario where the sponsor’s product contains a substance that occurs naturally in the body and the sponsor uses available GASK information about the substance and its effect, in lieu of conducting nonclinical studies. The second scenario is one where a sponsor has shown the impact a drug has on a particular pathway and then uses GASK information to show that impact rather than conducting clinical studies.

“The examples discussed in this guidance reflect areas where we have previously determined that it was appropriate to rely on GASK to meet certain requirements for approval,” said FDA. “Notably, while the examples provided here are for illustrative purposes, determinations regarding the appropriateness of data submitted for any application, including GASK, are fact-specific, and the question of whether certain information can be considered GASK and the purpose such information would serve in an application will be considered in the context of a particular application.”

“If a sponsor believes that certain information is GASK, the sponsor should submit their rationale to the review division as early as possible in product development to obtain feedback with respect to the proposed regulatory strategy for approval,” the agency added. “The submission should include relevant evidence supporting GASK, including textbook excerpts and/or non-product-specific published literature.”

Stakeholders can comment on the draft guidance until 23 July on www.regulations.gov under docket no. FDA-2023-D-1618.

Draft Guidance

FDA drafts guidance on using ‘generally accepted’ knowledge to support drug approvals

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