Designing non-clinical toxicity studies is challenging for any new product due to several guidance documents providing seemingly similar but different perspectives on regulatory requirements. This week the FDA released a guidance document describing strategies for non-clinical study plans for oligonucleotide products.
More than 20 guidance documents describe the non-clinical study requirements for all drugs and biologics. Together these guidance documents suggest more than 100 different non-clinical study designs based on the nature of the investigational product, the stage of development, and numerous confounding conditions. For example, the most prominent non-clinical guidance for the last two decades, the ICH M3-R2 guidance, describes more than 10 distinct toxicity studies. The main challenge with designing the non-clinical testing program for any new product is understanding the intent of a given tox study. On top, the guidance documents are dated, so when new technologies are being developed, it is harder to apply the principles previously described for such new technologies.
The new guidance on non-clinical tox studies with oligonucleotide products such as antisense sequences, small interfering RNA, microRNA, transfer RNA, decoys, and aptamers, addresses a detailed plan for safety and toxicity assessments that should be invaluable to the developers of these products. The guidance discusses the key studies, the selection of animal species, the timing of the studies, and other issues. It provides references and connections to previous guidance documents.
This guidance is all one would need to plan the entire non-clinical testing plan for oligonucleotide products.
