Physicians Committee Policy Work Pushes FDA to Launch Pilot Program to Evaluate and Accept Nonanimal Approaches in Drug Development

But recent news from the U.S. Food and Drug Administration (FDA) presents a new path forward, a means to move away from this practice. Just this week, the FDA launched a pilot program, Innovative Science and Technology Approaches for New Drugs (ISTAND), that will help integrate scientific tools and technologies that use human biology to predict human outcomes. 

Behind the Scenes

For the past five years, the Physicians Committee maintained a laser-like focus on ending animal tests in drug development. In early 2017, we hosted a roundtable at our Washington, D.C. headquarters that pulled together representatives from the FDA, the National Institutes of Health, pharmaceutical companies, academia, patient organizations, research organizations, and developers of human biology-based in vitro and computational approaches. The roundtable aimed to identify barriers to use of nonanimal tools and technologies and to provide action items for moving the field away from animal studies toward more predictive methods. 

Through a series of ongoing meetings, the group evolved into the Nonclinical Innovation and Patient Safety Initiative (NIPSI). NIPSI is a broad group of drug development stakeholders collaborating to improve the human-relevance of drug testing by taking a holistic approach to change, that includes policy, science, training, and outreach. Physicians Committee staff led the projects and partnered with different organizations on diverse activities. 

One of the barriers to the use of new approaches identified by industry and test method developers was lack of a pathway for acceptance of nonanimal approaches. Some thought that in vitro and computational approaches might fit within the existing Drug Development Tools Qualification Program (DDT) at FDA, but over time it became clear that this was not going to work. We had to ensure a path for FDA acceptance of nonanimal approaches was established.

Never Relenting

To convince the agency that this was needed, we spent the last five years providing formal input at FDA meetings on the DDT program, at stakeholder meetings on the FDA’s Predictive Toxicology Roadmap, and at the stakeholder meeting on the reorganization of the Office of New Drugs, and we encouraged other stakeholders to do the same. We also included the need for this pathway in our input to the Interagency Coordinating Committee on the Validation of Alternative Methods and to the Scientific Advisory Committee on Alternative Toxicological Methods, which are two committees that influence the FDA. Along with industry partners, we met with leaders at the Center for Drug Evaluation and Research (CDER) at the FDA to discuss the need for such a program. We also worked with industry to host a Congressional briefing on the issue that led to Congress sending a formal inquiry to the FDA Commissioner, requesting that the FDA’s existing DDT be expanded to include nonanimal methods, and we supported the House of Representatives and the Senate in passing Appropriations funding language making the same request of the FDA. We knew we were making progress when Elizabeth Baker, JD, the Physicians Committee’s pharmaceutical policy program director, co-authored a manuscript with FDA authors that described the need for this program, then the FDA published a manuscript indicating that the FDA had heard us and acknowledging that the program was being explored.

Hard Work Paid Off

The FDA launched ISTAND to expand its ability to qualify drug development tools that are outside the scope of the DDT program. Qualification is intended to provide a pathway for new approaches to be integrated into regulatory decision-making. However, the DDT program is limited to three programs (biomarkers, clinical outcome assessments, and animal models under the animal rule) and excluded the vast majority of nonanimal in vitro and computational approaches. In vitro and computational approaches may now be qualified with the FDA under ISTAND.

ISTAND is a game changer. It removes regulatory barriers to use of nonanimal and human biology-based approaches that are qualified via the program.

Traditional animal studies are accepted by default, meaning drug sponsors can be confident that the FDA will accept them. Conversely, nonanimal and human biology-based approaches are accepted on a case-by-case basis, meaning drug developers that seek to use them must pitch the agency and provide extensive evaluation studies each time the company wants to use the approach; this adds time and work to an already lengthy and costly process and dissuades companies from using new approaches.

Scientific evaluation is crucial to understanding the strengths and limitations of a new approach. ISTAND now provides an avenue for both pharmaceutical companies and test developers to work with the agency to review a tool for regulatory acceptance. Once a method is qualified via ISTAND, drug developers can confidently use the method for its qualified purpose, without the additional case-by-case work.

What’s Next

Now that ISTAND has launched, our work has shifted to supporting pharmaceutical companies and technology developers in swiftly submitting ISTAND applications, and offering support to the FDA as it works through the pilot program to establish a lasting program that efficiently integrates human biology-based approaches into drug development in lieu of animal studies. 

While we celebrate this historic victory for humans and animals, we are ever more determined and motivated to see this effort through to its end and to our ultimate goal: an end to animal use in drug development, and the elevation and acceptance of nonanimal and human biology-based methods.