Only the FDA Modernization Act 2.0 Can Ultimately Prevent More Abuses of Primates, Beagles and Other Mammals Harmed by Inotiv and Its Subsidiaries
Earlier this year, it was a horror show for beagles at Envigo, an animal breeding facility that supplies pharmaceutical companies and their contract facilities for their animal-testing work. Now Envigo’s parent company, Inotiv, is at the center of a mass smuggling operation of endangered non-human primates trapped from the wild and also sold for use in U.S. laboratories.
Last month, the U.S. Department of Justice indicted eight people alleged to be at the center of an international monkey smuggling ring tied to Inotiv. Inotiv houses approximately 9,000 monkeys for sale to drug developers for experiments, and conducts nonclinical animal testing in-house. Now we have more insights than ever about the trappers and traffickers who fill up their cages at its obscure facilities.
Earlier this year, the U.S. Department of Justice shut down the Envigo beagle breeding facility in Cumberland, Virg., after PETA and the U.S. Department of Justice exposed systemic mistreatment of the dogs. With Envigo repeatedly failing to comply with orders to fix deficiencies noted by animal-care inspectors at the U.S. Department of Agriculture, a U.S. District Court Judge ordered Envigo to surrender all beagles. That surrender of more than 4,000 beagles was the largest transfer of dogs from a laboratory animal breeding facility to animal welfare groups in the 57-year history of the Animal Welfare Act.
It all comes in the wake of the campaign by the Center for a Humane Economy and Animal Wellness Action to eliminate a federal animal-testing mandate that has for eight decades driven use of tens of millions of dogs, beagles, and other animals in drug screening protocols. The annual toll of animal life is in the millions, despite data incontrovertibly demonstrating that animal tests are reliably miserable forecasters for the human response to experimental drugs.
These two cases — first with the beagles at Envigo and now with the non-human primates at Inotiv — put a fine point on the need for national legislation, with Congress poised this week to include the FDA Modernization Act in a massive end-of-year spending package to end the era of mandated animal testing. A revamped drug development paradigm promises to reduce drug development costs for the companies that do this work, lower costs for patients and deliver safer drugs to them, and spare millions of animals in the process.
Inotiv and Subsidiaries in Spotlight Over Beagle Mistreatment, Primate Smuggling
With news of the primate smuggling scandal, Inotiv’s stock dropped 25 percent on Friday. Prior to that, Inotiv shareholders had demonstrated that they were none-too-pleased with the earlier Envigo scandal over the beagles. Shareholders filed a class action lawsuit alleging Inotiv “made materially false and misleading statements throughout the Class Period. Specifically, Plaintiff alleges that Defendants failed to disclose that: (1) Envigo and Inotiv’s Cumberland, Virginia facility (the “Cumberland Facility”) engaged in widespread and flagrant violations of the Animal Welfare Act (“AWA”); (2) Envigo and Inotiv did not properly remedy issues with regards to animal welfare at the Cumberland Facility; (3) as a result, Inotiv was likely to face increased scrutiny and governmental action; (4) Inotiv would imminently shut down two facilities, including the Cumberland Facility; and (5) Inotiv did not engage in proper due diligence.”
The details on the primate case may be even more incriminating for the company. A review of Inotiv’s SEC filings shows that on June 15, 2021, Envigo was served with a grand jury subpoena issued by the Department of Justice in Miami requiring the production of documents related to the importation into the United States of live non-human primates originating from or transiting through China, Cambodia, and Vietnam from April 1, 2014, through March 28, 2019.
In November 2022, the United States District Court, Southern District of Florida, issued an indictment charging two Cambodian wildlife officials and several members of a Hong Kong-based primate-supply company with illegally exporting hundreds—and potentially more than 2,000— cynomolgus macaques, an endangered species, to the United States for testing. The charges include conspiracy and smuggling. The U.S. leads the world in the number of primates it imports for medical research. Between 2017 and May 2022, more than 150,000 monkeys arrived in the U.S. to be used in experiments, according to figures from the Centers for Disease Control and Prevention.
The indictment names two unindicted co-conspirators — one U.S. company located in the Southern District of Florida, the other in Alice, Texas. Inotiv acquired Orient Bioresources, in Alice earlier this year. It is described as a quarantine and holding facility for non-human primates. Inotiv’s Envigo also has a research facility there, too.
Inotiv acquired Orient BioResource center five months after the company’s vice president received a felony conviction for lying to federal agents during their investigation into monkey trafficking.
The animals were reportedly captured from the wild in Cambodia and falsely labeled as captive-bred. According to the U.S. Centers for Disease Control and Prevention, in the 12 months ended September 30, 2022, approximately 60 percent of the non-human primates imported into the U.S. came from Cambodia.
According to Science, the removal of cynomolgus macaques from the wild is not sustainable. While the actual number of these monkeys in the wild is unclear, the International Union for Conservation of Nature changed the status of the monkeys from vulnerable to endangered this year, citing growing demand from the research industry as an ongoing threat to their survival.
The conspiracy to pass off wild and endangered macaques as purpose-bred in a laboratory is a common public-relations ploy by some laboratories. From 2000 to 2020, wildlife traffickers imported approximately 482,000 primates to the U.S. for laboratory use. Primates are wild animals, whether captured and removed from their wild habitat, or bred for research. Monkeys evolved to live in highly social groups of other monkeys and range over large areas. Their life expectancy in the wild can exceed 40 years.
Congress Has Even More Reasons to Pass the FDA Modernization Act Now
“We believe that, depending on the duration of restrictions on these imports, drug discovery and development in the U.S. could be materially impacted,” wrote Inotiv’s management team in a December 2022 business update to its shareholders that was foreboding about the prospect of a shortage of wild-caught primates for use in U.S. laboratories. “NHPs are critical for scientific research, and are required by international regulatory guidance to develop and evaluate the safety and effectiveness of a range of life-saving drugs and treatments prior to their assessment in human clinical trials. Historically, the U.S. biomedical industry has relied on imported NHPs [non-human primates] to meet its domestic demand for research and development of new medicines.” (emphasis added)
That “required” testing has been in the crosshairs of Animal Wellness Action and the Center. Both the U.S. Senate and U.S. House have passed our FDA Modernization Act to lift the mandate, but the House and Senate must take additional action this week to enact the measure.
The FDA Modernization Act, led by Senators Rand Paul, R-Ky., and Cory Booker, D-N.J., and by Reps. Vern Buchanan, R-Fla., and Elaine Luria, D-Va., would eliminate a Depression-era statutory mandate for animal testing for any new drug development protocol and, instead, allow the best scientific methods to be used for safety and efficacy testing.
Decades of research on non-human primates, bred and housed to be used for diseases like HIV/AIDS and Hepatitis C, didn’t lead to treatments or vaccines. One study revealed that of 85 potential AIDS vaccines tested in 197 human trials, only seven reached Phase III trials, and not one vaccine was successful after passing muster in chimpanzees. In short, years of research and the sacrificing of chimpanzees and other primates yielded little of value for the human condition, diverting resources from other more promising pathways and racking up a major opportunity cost.
In 2015, the National Academy of Medicine determined that experimentation on chimpanzees was unnecessary, and the National Institutes of Health (NIH) determined that chimpanzee experiments “rarely accelerated new discoveries or the advancement of human health for infectious disease,” paving the way for a ban on the use of chimpanzees in invasive experiments in the United States. While that was a long overdue and welcome action, it did not solve the problem of painful, unneeded testing on non-human primates. Laboratory scientists quickly pivoted to monkeys as a substitute, with rhesus, cynomolgus macaques, and African green monkeys used as stand-in victims for the chimps.
Data from monkey experiments for SARS and Middle East Respiratory Syndrome (MERS) did not prove valuable. Yet laboratory scientists doubled down on primate use for SARS-CoV-2, with so many of the animals used that a shortage in the primates resulted. Monkeys, mice, and hamsters tend to develop milder disease symptoms than humans, if they get sick at all, making it hard to test new medicines.
Even while the use of primates surged, there was a coordinated effort with the vaccine development world to apply 21st-century science in the battle against SARS-CoV-2 using nonanimal technologies. For example, the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICETM) has joined other government agencies and global partners to apply advanced non-animal technologies for COVID-19 research. Even Pfizer and Moderna realized that mRNA vaccines work very differently in animals compared to humans, and they delayed many animal efficacy studies and opted to go directly into human clinical trials. The law nonetheless requires these concurrent tests on animal, wasting countless millions of dollars and the lives of untold numbers of animals.
The law has drug developers, and, to a far greater degree, the animals in a vise grip. Only Congress passing the FDA Modernization Act 2.0 will remedy the problem. When the FDA accepts non-animal testing data, we’ll see a year-by-year reduction in the use of dogs, primates, rabbits, mice, and other creatures and an end to the mismanagement and torment of domesticated and wild animals, including the trapping and harming of endangered species.
Almost all major research organizations, pharmaceutical companies, academic institutions, and even government agencies have embraced the broadly accepted construct of the “3Rs” approach — Reduction, Refinement, and Replacement — to animal testing. The FDA Modernization Act 2.0 will finally allow many key players in drug development and in government to act on the 3Rs promise.
Indeed, these key actors in industry have a moral and scientific duty to use alternatives when the law permits. They’ll do better for their patients and their shareholders when they make the switch to 21st-century screening strategies, dispensing with the legal and moral problems that plague the and tarnish an enterprise with the noble purpose of improving the quality and duration of human life.
Tamara Drake is director of research and regulatory affairs for the Center for a Humane Economy. Wayne Pacelle is president of the Center for a Humane Economy and Animal Wellness Action.