ISSCR consortium submits recommendations on NAMs to FDA

The International Society for Stem Cell Research (ISSCR) Consortium on Advanced Stem Cell-Based Models in Drug Discovery and Development has submitted recommendations to the US Food and Drug Administration (FDA) in response to the agency’s draft guidance on the use of new approach methodologies (NAMs) in drug development.

The consortium, which brings together academic researchers, industry representatives and regulatory experts from around the world, said it welcomed the FDA’s efforts to expand the role of NAMs while urging regulators to maintain a flexible framework capable of adapting to rapidly to these evolving technologies.

Support for evolving regulatory framework

The ISSCR consortium said the guidance was an important step towards modernising drug development by recognising the growing role of new approach methodologies.

“NAMs, including stem cell-derived models such as organoids, engineered tissues and computational systems, have tremendous potential to improve the predictive power, efficiency and human relevance of preclinical drug development,” said Shuibing Chen, Co-chair of the consortium. “The FDA’s draft guidance is an important step forward in supporting innovation while helping to establish needed framework for the use of NAMs in drug development.”

NAMs are growing as an alternative or complement to conventional animal models because they have the potential to better replicate human biology and disease. Researchers think these technologies could improve their ability to predict drug safety and efficacy earlier in development while reducing failures during clinical testing.

NAMs are growing as an alternative or complement to conventional animal models because they have the potential to better replicate human biology and disease

The consortium said the FDA should ensure its framework is adaptable as technologies are constantly advancing, particularly in areas like artificial intelligence, computational biology and stem cell engineering.

Recommendations for broader flexibility

In its response, the consortium praised the FDA for developing what it described as a clear principle-based framework focused on context of use, human biological relevance, technical characterisation and fit-for-purpose evaluation.

However, the group also proposed several recommendations intended to strengthen the guidance and support wider application across different NAM technologies.

Among its suggestions, the consortium called for greater clarity that the biological complexity of a NAM should match its intended purpose. This, it argued, would support the use of both simpler high-throughput systems and more sophisticated biological models depending on the application.

The consortium called for greater clarity that the biological complexity of a NAM should match its intended purpose

The consortium also urged regulators to evaluate NAMs not only by comparing them with traditional animal models but also by assessing their ability to generate human-relevant insights in areas where existing methods may have limitations.

Another recommendation focused on expanding recognition of computational modelling, artificial intelligence and hybrid in vitro and in silico approaches as important tools in modern drug development.

Focus on stem cell-derived systems

The group also highlighted the specific challenges associated with characterising stem cell-derived models, particularly induced pluripotent stem cell (iPSC)-based systems.

The consortium say that these technologies may require distinct regulatory considerations because of their biological complexity and variability.

It recommended that the FDA consider developing future guidance documents or hosting workshops focused specifically on stem cell-derived NAMs to support consistency in evaluation and regulatory expectations.

Now as regulatory agencies worldwide continue exploring alternatives to animal testing, the FDA’s evolving approach to NAMs will be important in growing future drug development strategies and standards across the pharmaceutical industry.