The Physicians Committee

Good Science

December 2017

December 12, 2017   organ on a chip


road map

Image Credit: FDA.

The Food and Drug Administration (FDA) has joined other drug development stakeholders in pushing for the development and implementation of more predictive preclinical testing approaches. Last week FDA unveiled its Predictive Toxicology Roadmap, which aims to transform the development, qualification, and integration of new toxicology methods across FDA centers.

Toxicology testing is crucial for the development of safe medical products that are regulated by FDA because it informs potential risk to humans. Traditionally, toxicity testing has used animals to make predictions about human outcomes. However, the quality of information gained from animal tests has been the subject of much debate.

For far too long animal-based toxicity tests have been accepted as the benchmark for testing despite a general failure to provide information that is sufficiently relevant to humans. For example, the FDA and drug development stakeholders have known for more than 13 years that approximately 92 percent of new medicines fail in humans after passing animal tests.

This Roadmap acknowledges the scientific advances made and establishes a plan for support and implementation.

In an article released on the subject, FDA’s acting chief scientist stated, “Today, novel methods such as organs on a chip or mathematical modeling are being developed for toxicity testing that are generating unique opportunities to improve our ability to quickly and more accurately predict potential toxicities and reduce associated risks.”

The six-part Roadmap seeks to improve toxicity testing and formalizes FDA’s position on replacing/reducing animal testing.

The Roadmap establishes a Toxicology Working Group to facilitate communication among FDA centers. FDA knowledge will no longer be siloed in separate centers, but will rather be shared to help determine which approaches may be used for which purposes.

The group will identify gaps in current test methods and determine where newer approaches—

such as organ chips and computer simulations—may be identified, further developed, scientifically evaluated, and implemented.

The group will also develop a Toxicology Seminar Series to facilitate agency-wide training on new testing approaches. We’ve pushed for this much-needed initiative through consistent input to FDA and ICCVAM, as agency scientists must build their knowledge-base, confidence and familiarity with modern approaches to toxicity testing.

The Roadmap encourages frequent and often communication with FDA regarding interest in using new methods. FDA should take this opportunity to update its regulations that mandate animal data, to ensure the Roadmap is properly implemented. Companies may not be willing to rely on the Roadmap in the face of inconsistent regulations.

The Roadmap solidifies FDA’s commitment to working with the stakeholder community, which has seemed to increase over the past year. In January 2017, FDA participated in a Preclinical Innovation and Patient Safety (PIPS) roundtable hosted by the Physicians Committee. The roundtable aimed to increase stakeholder collaboration to advance modern, predictive approaches. FDA has also collaborated with the National Center for Advancing Translational Sciences (NCATS) and the Microphysiological Systems Working Group of the IQ Consortium to provide input on tissue chip technology.

The Toxicology Working Group will track progress and provide annual reports to the chief scientist to increase oversight and accountability.

We applaud FDA for its transparency and vision set forth in the Roadmap, and look forward to continued collaboration to save human and animal lives.

Learn more from our The Hill op-ed and The Exam Room.


United States Department of Agriculture

In October, organizations that represent animal experimenters and their institutions released a troubling report. It proposes drastically cutting protections for animals in laboratories, including a significant change to the Animal Welfare Act.

The report, titled Reforming Animal Research Regulations, recommends weakening federal standards for animals in laboratories and also giving animal experimenters greater control over the creation of new rules. Essentially, it would help create an oversight system that allows laboratories to self-regulate.

A 2014 Pew Research Center survey of adults in the United States found that 50 percent of respondents "oppose" the "use of animals in scientific research” compared to 47 percent who "favor" the practice. Pair that level of concern with the federal government's poor enforcement of animal welfare in laboratories. In 2014, the U.S. Department of Agriculture’s (USDA) own Office of Inspector General (OIG) found:

  • USDA inspectors did not always review animal use protocols and annual reports (the documents that list how many of each species were used and in what pain category), as required.
  • USDA closed investigations involving grave Animal Welfare Act (AWA) violations, including animal deaths and serious repeat violations.
  • USDA failed to properly punish laboratories by reducing fines by an average of 86 percent – despite previous OIG recommendations to end this practice.
  • Some laboratories’ Institutional Animal Care and Use Committees (IACUCs) are not adequately monitoring their facilities.
  • USDA wasted resources by conducting more than 500 inspections at more than 100 facilities that hadn’t housed AWA-covered animals for more than two years.

All of this should be cause for greater protections for animals and improved openness about what happens inside laboratories. Yet the authors of the report suggest that the government actually pare back its requirements.

Some of the report’s recommendations include:

  • Drastically reducing how often most research facilities are inspected by the U.S. Department of Agriculture (USDA). This change would significantly impair the public’s ability to monitor those facilities’ compliance with the law.
  • Exempting many animal use requests (called protocols) from review by a laboratory’s full Institutional Animal Care and Use Committee when the protocols include "low-risk, noninvasive, or minimally invasive procedures." Instead, the report proposes allowing much animal use to be approved by only one or two members of the committee. But when Congress amended the Animal Welfare Act in 1985, it intended these committees to serve as groups of people, not simply individuals. In addition, even protocols that don’t involve invasive procedures are still harmful to animals, who will experience the stress of confinement, handling, and preparation for experiments. Also, there is no shortage of reported injuries and deaths to animals during routine laboratory practices, including animals who died of dehydration due to broken air conditioning or water feeders and animals who died when their cages were sent through industrial washers.
  • Giving animal experimenters greater control over the creation of regulations and stifling public input. The report’s authors suggest that "[n]ear-final documents should be reviewed by an external advisory committee of experts engaged in animal research from the regulated community before they are disseminated for public comment or final agency review." This suggests that the comments of animal experimenters and the facilities that employ them should be given more weight—or be the only comments considered—when making new rules.

At a time when there is more pressure than ever to reduce government regulation, it’s crucial that we stand up for the rules that give some modicum of protection to those who are most vulnerable. And that's what the Physicians Committee is doing. We’re working with other organizations to plan a strategic response to the recent report and the larger effort to weaken federal animal welfare regulations.