FDA Science Board recommends creation of centralized new alternative methods office

The US Food and Drug Administration should create a centralized office to coordinate work on new alternative methods (NAM) to evaluate regulated products while reducing dependence on animal testing. That was one message from a subcommittee of the FDA’s Science Advisory Board, presented at the board’s virtual meeting 7 October.

The board met to get an update from the agency on several issues, including the commissioner’s top priorities and its new reorganization, which has created a new unified Human Foods Program (HFP) and transformed the Office of Regulatory Affairs (ORA) into the Office of Inspections and Investigations (OII).

A centralized NAM office “will ‘signal’ to critical stakeholders and partners FDA’s commitment and seriousness to drive change with the adoption of NAMs, as appropriate,” the report stated. “This includes assuring impactful communication, focus and driving effective partnerships.”

The report also recommends that FDA develop metrics that can be used to evaluate the impact of the agency’s investment in NAMs, create a uniform framework to qualify NAMs, create a transparent and scientifically rigorous review process to evaluate product applications that use NAMs, invest in high-impact NAMs initiatives that can be used in regulatory decisions, and compile a central NAMs database.

NAMs could include technologies and methodologies such as in vitro tests, in silico computational models, biomarkers, and modified in vivo assays. The report noted that regulated industries have already made advances and adapted some NAMs to screen and identify compounds used in applications for approval. In most cases, such methods are used to find compounds for specific biological responses or provide insight into specific cell, organ, or molecular responses to address safety and efficacy questions.

In 2022, the FDA launched the NAM program, then called the New Approach Methods (NAM) program, which was intended to focus on the three Rs of replacing, reducing, and refining animal testing. The agency noted that, historically, it has used animal testing studies to understand the toxicity of substances it regulates. However, such studies can take years to complete, have certain limitations, and can be costly. The agency hopes to develop NAMs to reduce reliance on animal testing and improve the predictability of nonclinical testing.

Cynthia Afshari, a vice president at Johnson & Johnson and a board member, discussed how the subcommittee developed the NAM report. She noted that there's been increasing public pressure to eliminate the FDA's reliance on animal testing, which the agency supports.

"While we may not be able to do away with all animal testing, being able to recognize the three Rs and reduce either the number of animals in the study, [or] being able to increase the power of the data that we get from them, and certainly to refine the methods, is an important opportunity that should be considered in this scope of NAMs," Afshari said at the meeting.

"As of today, it's not likely that NAMs can fully reduce and eliminate all animal testing in the FDA product centers, and that's just because ... the state of the science is that not all organ systems are available for testing in that sphere of in silico and in vitro," she added. "However, we do expect that this will continue to evolve rapidly and that FDA is positioned to continue to take advantage of the emerging science."

David Strauss, acting FDA chief scientist, spoke during the meeting and noted that the agency’s drugs and devices centers already have alternative qualification programs that must be leveraged to advance the development of more NAMs.

“We can’t just have a goal of the three Rs, there needs to be other benefits and motivations… What could some of those benefits be?” asked Strauss. “[They can streamline] development of FDA-regulated products, bringing products to the US public more rapidly and more efficiently, and ensuring products are safe, effective and the patients can depend on them.”

Strauss said FDA needs to collaborate with industry, academia, and international regulators to help advance the development of NAMs. He also said that it is important to qualify NAMs, sometimes in parallel with traditional product development tools, so that the agency can endorse alternative methods in advance for a specific context of use so that stakeholders can have the predictability of the methods used to evaluate the data in product applications.

“We would like to expand processes to qualify alternative methods for regulatory use, provide guidelines to external stakeholders developing alternative methods, and fill information gaps with applied research to advance new policy and guidance development,” said Strauss.

The report said that FDA’s strategy isn’t to focus on NAMs being developed by industry but to look at opportunities for using NAMs in current and future regulatory decision-making.

“Importantly, note that technical limitations to current NAMs exist and, that today, no assays fully capture the critical hazard endpoints for assessing all currently existing human or animal organ systems; therefore, NAMs cannot fully eliminate the use of integrated physiological systems such as in animal and human trials,” the report said.

“While NAMs represent promising tools for decision-making, they are, in most circumstances, currently best used in conjunction with traditional methods and not as stand-alone solutions for hazard identification or human risk assessment,” it added. “However, this position will continue to evolve over the coming years and decades as some areas show promise for faster opportunities and rates for adoption than others – such as in vitro ‘barrier models’ for cosmetics or food testing, (e.g., drugs).”

Science Advisory Board Meeting; NAMs report

FDA Science Board recommends creation of centralized new alternative methods office

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