Moving away from animal models?

WASHINGTON, D.C.—It takes an average of 8.5 years and millions of dollars to get a drug through U.S. Food and Drug Administration (FDA) testing. Only about one in 5,000 chemicals makes it all the way through the testing. Is there a better way to determine the safety and efficacy of drugs?

A coalition of non-profit advocacy organizations, technology developers and patient interest groups has asked the FDA to update regulations that govern preclinical drug and device development. Led by the Center for Responsible Science (CRS)—a non-partisan, nonprofit organization advocating for more modern and predictive test methods in drug development—this coalition has filed an FDA Citizen Petition to streamline drug and device development. The coalition includes CRS, Asterand Bioscience, AxoSim Technologies LLC, Empiriko, Friends of Cancer Research, HµREL Corporation, In Vitro ADMET Laboratories, InvitroCue, InVitro International, MatTek Corporation, the National Organization for Rare Disorders, Safer Medicines Trust, United Spinal Association and 3D Biomatrix Inc.

Proponents want the FDA to ensure that safer and more effective medical products are available to patients. Explaining that FDA regulations mandate animal data, Dr. Robert Coleman, science advisor to CRS and Safer Medicines Trust, maintains that the current regulations should provide drug trial sponsors with the option to use human-based technologies that may be more predictive of human response.

The coalition argues that the most predictive technologies in existence should be available to drug sponsors as they work to provide the safest and most effective medicines for patients. According to animaltestingperspectives.org, many non-animal methods are approved and used today. Animals can be replaced by methods that do not involve animals at all or by those that use only the cells or tissues of animals. Replacement alternatives involve these in-vitro techniques, where the studies are done with cells or tissues in culture. Other alternatives include in-silico methods that replicate animals’ reactions through a computer program. While these methods are very useful for studies on particular types of tissue and help considerably to limit the number of animals used, they cannot simulate an entire organism with all its cells, tissues and systems working together.

“Current use of in-vitro methods in preclinical product testing include but are not limited to skin and eye irritation, genotoxicity, phototoxicity and pyrogenicity,” said Marc Scheineson, regulatory attorney with Alston & Bird and the coalition’s representative. “Sponsors also use proprietary in-vitro assays. In-vitro and in-silico tests are also used in early product development, toxicology and absorption, distribution, metabolism and excretion (ADME) and pharmacokinetics.”

According to Dr. Troy McCall, advisor to and member of the CRS board of directors, “The ultimate focus should be on which technologies work best and are most predictive, regardless of whether the data are animal-based or not.”

At issue for the coalition is that animal models, whether they actually sacrifice animals or not, aren’t always very predictive, and the FDA needs to become amenable to other preclinical models that are more oriented toward human function.

The petition, which includes stark statistics on drug development that support the coalition’s focus on development and use of safer, more effective and less expensive preclinical test methods, claims that 95 percent of drugs found safe in preclinical tests later fail during human clinical trials because of their toxicity and/or lack of efficacy. Proponents want the FDA to update the regulations, because more predictive tests likely mean faster development times.

“In-vitro and other non-animal test methods (NATMs) are not available for all regulatory needs to support Investigational Drug Applications and Investigational Device Exemptions,” Scheineson says. “However, cutting-edge technology is available that will provide more accurate results, more cheaply and more quickly. A change in FDA regulations will encourage development and use of these technologies which, in turn, will generate more accurate and useful preclinical data.”

He adds that “U.S. government agencies have invested millions of dollars on development of NATM technologies. Organ-on-a-chip technology, 3D printed organs and other technologies are advancing at a rapid pace. As individual organs-on-chips are improved, it is possible to progressively replace one animal-based assay at a time.”

Scheineson concludes, “This small step for FDA will lead to more efficient drug and device development. We believe FDA will view this petition as a worthwhile project that is consistent with FDA’s initiative to advance regulatory science.”