28 years later, FDA is “replacing animal testing,” new chief Makary says

Makary finally does what the FDA,  EPA,  & National Institutes for Health were petitioned to do in 1997,  50 years after key technology became available

WASHINGTON D.C.––U.S. Food & Drug Administration commissioner Martin Makary on April 10, 2025 announced barely two weeks after taking office that the FDA is “replacing animal testing in the development of monoclonal antibody therapies and other drugs with more effective,  human-relevant methods.”

The Makary announcement came 50 years after non-animal-using monoclonal antibody testing methods were developed,  becoming available in 1975.  Makary at the time was only two years old.

The Makary announcement also came almost 28 years to the day after the American Anti-Vivisection Society in April 1997 petitioned all government agencies using monoclonal antibodies to adopt the non-animal approaches.  Makary then was working on his master’s degree in public health.

“Reduced,  refined,  or potentially replaced”

Said Makary specifically in his April 10,  2025 prepared statement,  “The FDA’s animal testing requirement will be reduced,  refined,  or potentially replaced using a range of approaches,  including AI-based computational models of toxicity and cell lines and organoid toxicity testing in a laboratory setting.”

The Makary statement appeared to deliberately invoke the “Three Rs” pathway for eliminating animal testing outlined in 1959 by British scientists William Russell (1925-2006) and Rex Burch (1925-1996).

“Implementation of the regimen will begin immediately for investigational new drug applications,”  Makary continued.

“To make determinations of efficacy, the agency will also begin use pre-existing,  real-world safety data from other countries,  with comparable regulatory standards,  where the drug has already been studied in humans.

“A paradigm shift in drug evaluation”

“For too long,”  Makary said,  “drug manufacturers have performed additional animal testing of drugs that have data in broad human use internationally.

“This initiative marks a paradigm shift in drug evaluation and holds promise to accelerate cures and meaningful treatments for Americans while reducing animal use.

“By leveraging AI-based computational modeling,  human organ model-based lab testing,  and real-world human data,  we can get safer treatments to patients faster and more reliably,”  Makary promised,  “while also reducing research and development costs and drug prices.”

A six-paragraph addenda to Makary’s statement outlined “key benefits of replacing animal testing in monoclonal antibody safety evaluation,”  explaining that “software models could simulate how a monoclonal antibody distributes through the human body and reliably predict side effects based on this distribution as well as the drug’s molecular composition.

“Organ-on-a-chip systems”

Also,  “The FDA will promote the use of lab-grown human ‘organoids’ and organ-on-a-chip systems that mimic human organs – such as liver,  heart,  and immune organs – to test drug safety. These experiments can reveal toxic effects that could easily go undetected in animals,”  Makary said,  “providing a more direct window into human responses.”

In addition,  Makary said,  the FDA “will work to update its guidelines to allow consideration of data from these new methods.  Companies that submit strong safety data from non-animal tests may receive streamlined review,  as the need for certain animal studies is eliminated,  which would incentivize investment in modernized testing platforms.”

Makary promised “close partnership with federal agencies such as the National Institutes of Health, the National Toxicology Program,  and the Department of Veterans Affairs,  to accelerate the validation and adoption of these innovative methods through the Interagency Coordinating Committee on the Validation of Alternative Methods.

“Non-animal-based testing strategy”

Further,  Makary said,  “Over the coming year, the FDA aims to launch a pilot program allowing select monoclonal antibody developers to use a primarily non-animal-based testing strategy, under close FDA consultation.  Findings from an accompanying pilot study will inform broader policy changes and guidance updates expected to roll out in phases.”

“This first action of commissioner Makary begins a new era for drug testing,”  enthused Physicians Committee for Responsible Medicine director of research policy Elizabeth Baker.

“While I’m always cautious about believing grand promises from federal agencies,  it was an incredible thrill to see those words uttered by a leader of the FDA,”  responded Center for a Humane Economy and Animal Wellness Action president Wayne Pacelle.

“At long last,  we may be at a pivot point where FDA is no longer obstructing the move away from animal testing,”  Pacelle said.

FDA Modernization Act 3.0

Pacelle himself then pivoted to plug the FDA Modernization Act 3.0,  recently introduced into the House of Representatives as ”a companion bill to the bipartisan Senate bill S.355,”  co-authored by Senators Cory Booker,  a Democrat from New Jersey,  and Eric Schmitt,  a Republican from Missouri.

The FDA Modernization Act 3.0 would “require the FDA to publish a final rule to implement the FDA Modernization Act 2.0,”  passed in 2033 by the 117th Congress,  requiring “updating regulations that allow for non-animal test methods.

“A nearly identical bill passed the Senate by unanimous consent in December 2024,  but the House did not take up the measure before the end of the 118th Congress” in January 2025,  Pacelle noted.

“The FDA Modernization Act 2.0,”  Pacelle argued,  “was,  without question, the most important policy change in the nation’s history to address animal testing.  The bill eliminated an 84-year-old animal-testing mandate for every new drug in development.

“The FDA Modernization Act 2.0 did not ban animal testing,”  Pacelle acknowledged,  “but it offered drug sponsors the option to use 21st-century alternatives such as cell-based assays,  organ chips,  computer modeling,  and bioprinting.”

“Launch & then falter”

Agreed Humane World for Animals president Kitty Block and Humane World for Animals Legislative Fund president Sara Amundson,  in a joint blog focusing on animal use in Environmental Protection Agency testing,  rather than on the Makary announcement pertaining to the FDA,   “Over the years, we’ve seen a series of initiatives within the EPA and other federal agencies launch and then falter.

“With respect to the EPA,”  Block and Amundson explained,  “the agency has traditionally relied on animal tests to assess the probable effects and toxicity thresholds for human exposure to chemicals and pesticides.

“Our history with this issue goes back at least as far as the Clinton administration’s proposal for a High Production Volume Chemical Testing Program to expand the number of animals used in tests.  We moved quickly to negotiate a firm commitment to the reduction and elimination of new testing,  and we helped to secure dedicated funding to support those goals at both the EPA and the National Institute of Environmental Health Sciences.

Toxic Substances Control Act

“We led the campaign to reform the Toxic Substances Control Act,”  Block and Amundson claimed,  “making it the first federal statute to call for an end to new animal testing.”

Both Block and Amundson helped to lobby for the 2016 passage of the Toxic Substances Control Act reforms adopted in 2016,  but Wayne Pacelle at the time headed both of their parallel organizations,  then known respectively as the Humane Society of the U.S. and the subsidiary Humane Society Legislative Fund,  titularly led by HSUS vice president Mike Markarian.

Block and Amundson also mentioned a 2024 “legal petition to modernize FDA regulations  and guidance governing testing for new drug approvals,”  paralleling the 1997 petition from the American Anti-Vivisection Society,  which was immediately rejected by then-National Institutes of Health director Harold Varmus.

Private companies

“Most EPA-related testing involves private companies’ submissions for registration of chemicals and pesticides,”  Block and Amundson continued.

“For that reason,  we have also concentrated on accountability for corporations seeking regulatory approval.  We have pushed them to make their own strong commitments to reduce and eliminate animal tests.”

This was the approach,  highly controversial at the time,  pioneered by Animal Rights International founder pioneer Henry Spira (1927-1998) in securing pledges from Avon and Revlon to quit animal testing in 1980,  and from Procter & Gamble in 1984 to fund development of alternatives to animal testing. Procter & Gamble has now invested more than $480 million in fulfilling that pledge to Spira,  developing more than two dozen non-animal testing methods now in use by companies all over the world.

“We have also worked directly with the scientific community worldwide to address the scientific challenge of moving away from animal use,”  Block and Amundson said,  citing a “recent collaboration with the EPA’s Office of Pesticide Programs staff” that “resulted in a published paper showing that an in silico [computer] model is a suitable replacement in most cases for an acute toxicity test in which rats are fed increasing doses of pesticides.”

Saving mouse lives

The American Anti-Vivisection Society petition to replace monoclonal antibodies extracted from animals was introduced in April 1997 by then-AAVS director of special projects David Cantor with an abortive media campaign titled “Antibodies Without Animals.”

Cantor explained that regulatory and procedural changes in monoclonal antibody production could save a million mouse lives a year,  largely through  adoption of an alternate production method that American Anti-Vivisection Society funding had helped to perfect.

The campaign drew favorable notice from the trade magazine Lab Animal,  and from a variety of scientific,  technological, and legal journals,  but none from mainstream mass media.

What are monoclonal antibodies?

Cantor left the American Anti-Vivisection Society after six months to found his own organization,  Responsible Policies for Animals.

Then-American Anti-Vivisection Society executive director Tina Nelson,  who headed AAVS from 1995 until her death in 2005,  took over the campaign.

As Nelson’s first priority,  she issued a simplified description of what it was all about.

“Monoclonal antibodies,”  Nelson explained,  “are used in essentially every field of human and veterinary research,  and in diagnosing and treating many cancers,  bacterial and viral infections,  and other ailments.

“They are especially useful because they attack specific antigens within the body,  where they are used to identify and/or destroy foreign materials.

Obsolete methods

“Unfortunately,  many laboratories still use the outdated and painful ascites method of producing monoclonal antibodies.  When animals are used,” Nelson described,  “tumor cells are injected into their abdominal fluid.  This causes ascites––a painful swelling of the abdominal peritoneal cavity.  It is estimated that more than one million animals,”  most or all of them mice,  “undergo this torment each year in the U.S.

“Since 1975,”  Nelson explained,  “scientists have known that monoclonal antibodies could be produced without the use of animals, but animal use proliferated in small-scale production.

Europe was 28 years ahead of the U.S.

“The alternatives are so simple,  reliable,  and economical,”  Nelson said,  “that the Netherlands,  Germany, and Switzerland have banned the use of animals.

“In April 1997,  the European Centre for the Validation of Alternative Methods published its recommendation that the entire European Union prohibit animal monoclonal antibody production.”

The U.S. lagged behind,  Nelson indicated,  as it still does,  in part because Animal Welfare Act enforcement regulations exclude mice,  rats,  and birds from the definition of “animal.”

USDA rewrote nature

The USDA Animal & Plant Health Inspection Service introduced this rewrite of nature in 1970 to avoid having to attempt broader Animal Welfare Act enforcement.

After many previous efforts failed,  an American Anti-Vivisection Society subsidiary called the Alternatives Research & Development Foundation won a series of judicial rulings that in October 2000 caused the USDA to agree to rewrite the regulations to protect rats,  mice,  and birds.

But Congressional budget amendments repeatedly delayed any actual rewriting until 2002,  when an Animal Welfare Act amendment introduced by U.S. Senator Jesse Helms (1921-2008),  a Republican from North Carolina,  made the exclusion of rats,  mice,  and birds from the definition of “animal” permanent.

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