The USFDA continues to innovate its regulatory landscape with the release of three important guidance earlier today (27 November, 2024) aimed at advancing drug development and ensuring patient safety. These guidances target different facets of pharmaceutical research, ranging from the use of liquid biopsy techniques in oncology to mitigating genetic and reproductive risks in drug development. Let’s explore these newly released guidances and their implications.
This guidance is intended to assist sponsors who are preparing to conduct cancer clinical trials utilizing circulating cell-free plasma-derived tumor DNA (ctDNA) as a biomarker under an investigational new drug application (IND) and/or in support of the approval of drugs and biological products for treating solid tumor malignancies at an early stage (curative-intent).
In this guidance, the FDA explains its current viewpoint on drug development and clinical trial design issues relating to the use of ctDNA as a biomarker in clinical trials for solid tumor malignancies for curative purposes. We will also discuss the standardization and harmonization of ctDNA assays and methodologies, focusing on the use of assays to detect molecular residual disease (MRD).
Guidance: Recommended Follow-Up Testing for an Ames-Positive Drug or Metabolite in First-in-Human Trials
This draft guidance makes recommendations regarding follow-up testing of active ingredients with Ames positivity when a sponsor decides to continue development. According to the guideline, a consistent follow-up testing and evaluation process should be implemented for active ingredients with Ames positivity before attempting first-in-human trials. These recommendations are intended to potentially help address and lower safety concerns before proceeding with FIH trials in healthy human subjects.
The Ames test is a widely used assay to evaluate the mutagenic potential of chemical compounds. Positive results may indicate a drug’s potential to cause genetic mutations.
The assessment of ovarian toxicity has become a critical component of drug development, especially for oncologic drugs that may pose reproductive risks to premenopausal women. This draft guidance provides recommendations to sponsors regarding the measurement of ovarian toxicity using clinical measures and biomarkers of ovarian function in relevant cancer clinical trials that enroll premenopausal adults with ovaries. Encourages conducting dedicated studies to evaluate ovarian reserve, hormonal disruption, and long-term fertility outcomes and suggests using biomarkers such as anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) to monitor ovarian function during and after treatment.
For more information, refer to the full guidance:
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