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August 14, 2017   government/food policy

 

Ask the FDA to modernize preclinical testing

Health IT Now—a broad-based coalition of patient groups, provider organizations, employers, and payers that develop and advocate for policy supporting health information technology to improve patient outcomes—requested the Food and Drug Administration include preclinical innovation in implementation of the legislation 21st Century Cures.

In January 2017, Health IT Now attended a roundtable—hosted by the Physicians Committee—to discuss the need for modernizing preclinical tests. Participants included federal agencies, pharmaceutical companies, academics, technology companies, and patient, health, and research organizations. Discussions included scientific, legal, policy, educational, and training opportunities that should be addressed in order to advance the field.

The FDA requires pharmaceutical companies to test all potential new medicines in animals during preclinical tests. Preclinical tests are meant to help scientists understand how a drug will fare when given to humans. Will it be safe or toxic? Will it be effective?

While “preclinical” was once interchangeable with animal tests, the prevalence and promise of innovative, new technologies, such as organ chips, computer simulations, and 3-D bioprinting are on the rise. As Health IT states in a recent letter to the FDA commissioner, “New technologies that would allow scientists to ‘fail faster’ would reduce waste, speed up innovation, and most importantly deliver safe and effective treatments to more patients who need them.”

The legislation 21st Century Cures requires the FDA to host a public meeting and issue guidance on novel clinical trial designs. Health IT Now’s letter to the FDA commissioner requests that the FDA include preclinical innovation, as “it would be a missed opportunity for the FDA and stakeholders to not include the transformative potential of technology in the entire drug development process, including preclinical testing.”

 

August 3, 2017   animal testing

 

European Medicines Agency Recommends Human-Based Tests After Fatal Drug Disaster

Seven out of 10 Americans take at least one prescription drug every day. Regulatory agencies, such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) work to ensure these drugs are safe for human use, from the first time they are tested in humans to market approval.

Prior to human testing, pharmaceutical companies conduct preclinical tests—primarily in animals—to help understand how the drug may interact with the human body. The utility of these tests is questionable, as the National Institutes of Health reports that more than 95 percent of potential medicines fail in humans after appearing safe in animals.

Last year, a previously healthy man died and four others experienced brain damage during a clinical trial in France. An extensive investigation concluded that the potential medicine being studied, BIA 10-2474 (BIA), caused Guillame Mollinet to die, and caused varying degrees of brain damage in the four others who were hospitalized.

As a result of this tragedy, the EMA began revising its regulatory guideline on risk mitigation for first-in-human and early clinical trials to further assist stakeholders in risk mitigation and translational issues. While the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines that include requests for animal data still apply, this guideline adds that additional approaches involving in vitro human cell systems or human-derived material may be useful for risk assessment by providing relevant information about translational differences.

The updated guideline also states that scientifically sound nonanimal tests should be used wherever possible.

A recent study supports the addition of human-focused approaches to preclinical assessment. Following up on the BIA disaster, a group of international researchers sought to find out why BIA was not safe by using activity-based protein profiling (ABPP) to screen BIA using human cells and brain tissues.

Researchers found that BIA disrupted the activity of several lipases, including an off-target enzyme that has been linked to neurological disorders, suggesting BIA may disrupt how neurons in the brain metabolize lipids. The off-target effects found using ABPP were not seen in preclinical experiments on mice, rats, monkeys and dogs. If the additional human-based test was conducted on BIA as part of preclinical screening, BIA may not have continued to animal tests and human trials.

The EMA guideline, which goes into effect in January 2018, is an important step toward improving the predictability of preclinical approaches that are meant to protect humans. In response to a tragedy, the EMA assessed and revised its practices.

The FDA should follow in its footsteps and work to revise its regulations and guidance that prioritize animal data, by clearly communicating that sufficiently evaluated human-based approaches are accepted in drug development.

 

July 27, 2017   animals in education

 

Baltimore Deserves Better

At the Physicians Committee, our efforts to end the use of animals in medical training are a big part of who we are. Currently, we are working to ensure that areas of advanced medical training—including emergency medicine residencies, Advanced Trauma Life Support courses, pediatrics residencies, and paramedic training programs—exclusively use human-relevant methods like simulators

You often see—and participate in—our demonstrations and letter-writing campaigns to get institutions to stop using animals. But there’s also a lot of activity going on behind the scenes of each campaign. We survey institutions to determine which are using animals and which are not, file requests using state and federal public records laws, review and summarize the stacks of documents we obtain from those requests, and diligently amass information regarding human-relevant training methods.  

Before we ever launch a public campaign, we write to faculty members and administrators at the medical center that is using animals. Sometimes they review this information and replace animals, and we commend them. 

But it’s usually not that easy. In those cases, we share the institutions’ practices with the public and media. Without fail, we have seen this approach succeed. But sometimes success comes slowly.

Consider Johns Hopkins University (JHU) in Baltimore, Md. In 2004, we learned that the university was once again using live pigs to teach surgical skills to medical students. After urging JHU to halt the practice, we learned in 2012 that it had reduced the number of animals used each year.

We kept the pressure on, holding physician-led demonstrations, posting local advertisements, and eventually delivering over 80,000 petitions from concerned citizens across the nation.

The beginning of the end came in January 2016, when Maryland Delegate Shane Robinson introduced a bill that would outlaw the use of animals for medical student training in the state. Four months later, Johns Hopkins announced it was ending its animal lab. But our work continues outside of medical student training.

Laval University in Quebec, Canada, is the only pediatrics residency program in Canada and the United States known to use animals—220 other facilities use only human-relevant training methods. 

When the Physicians Committee launched its public campaign against Laval in 2012, we revealed to the public that residents practice procedures on live piglets, which included making an incision between the animal’s ribs and inserting tubes and needles into the chest cavity, abdominal cavity, and under the breastbone to drain fluid from the sac surrounding the heart. The piglets are then killed before a surgical airway is performed. 

Recently, we obtained public records which revealed that Laval had made some changes to its animal use protocol, removing certain procedures because “animals are irrelevant…and considered to be non-representative of the human model.” In addition, the university’s Animal Care Committee only approved the protocol for two years—as opposed to three—“given the possible advances in artificial simulators.”

Based on these new findings, we filed a petition with the Quebec Ministers of Higher Education and Health and Social Services in April 2017, asking them to ensure that public funds are no longer wasted by Laval. We’re awaiting the outcome of the complaint.

In Minneapolis, our effort to end Hennepin County Medical Center’s (HCMC) animal use is also making progress. At HCMC, emergency medicine residents and other participants are instructed to practice over 20 procedures on live sheep and rabbits. 

In April 2016, we launched our public campaign against HCMC. Shortly thereafter, HCMC reduced the number of animals it uses by 100 each year. Just last month, the Star Tribune reported that “hospital officials said in a statement that they plan to eliminate the use of animals in its medical education program … HCMC said it is developing and testing new simulation technology that would replace the use of animals.” 

We await further developments from Laval and Hennepin. In the meantime, we’ll keep the pressure on them—and similar programs—by demanding that they provide the most educationally and ethically sound training available for future doctors and their patients.

If you would like to help us make certain that medical training is humane and exclusively human-relevant, please take action to support our active campaigns.

June 28, 2017   government/food policy

 

EPA budget proposal cuts research capabilities

Groundbreaking research to develop 21st-Century, nonanimal chemical assessment methods is at risk. Amazing examples include advanced robots that can screen thousands of chemicals at once, 3-D human livers that can test how humans metabolize pesticides, and a virtual embryo that predicts how chemicals will affect unborn children.

Sen. Tom Udall (D-N.M.), a sponsor of the 2016 Lautenberg Chemical Safety Act for the 21st Century, denounced plans to cut funding to the Office of Research and Development, calling the proposed budget “offensive.”

"I’m glad to hear you [EPA Administrator Scott Pruitt] say you support robust implementation of TSCA," Udall said. "Yet this proposal cuts programs that are vital to TSCA, such as the Office of Research and Development—cut in half—and core agency functions like enforcement. We can’t just build a wall around the TSCA office and expect it will perform."

When the Lautenberg Act passed Congress and was signed into law last year, stakeholders—including nonprofit organizations, labor advocates, and the chemical industry—celebrated. The new law gave the EPA important new powers—and responsibilities—to assess and manage chemical risks. The EPA must assess the tens of thousands of chemicals in the environment, starting with the most dangerous. It must affirm that new chemicals entering the market will be safe for their intended use. And it must consider the risks of chemicals on sensitive populations such as young children, and the risks of mixtures of chemicals.

Recognizing that our current test methods, mostly based on animals, are not up to this task, the authors of the Lautenberg Act required that the EPA and the chemical industry reduce and replace animal tests, and prioritize the development of new test methods and strategies that do not use animals. As required by the law, the EPA is currently drafting a strategic plan to develop nonanimal test methods that will help it assess chemical risks, for publication by June 2018.

The EPA must also prioritize from the thousands of chemicals in the environment to determine which are the most dangerous, for further study and regulation. With its Endocrine Disruptor Screening Program for the 21st Century, the EPA demonstrated how new tools can be used successfully. It has screened more than 1,800 chemicals using a set of in vitro rapid tests in combination with computer prediction algorithms, focusing government and private resources on high priority chemicals and saving tens of thousands of animals.

As it develops these groundbreaking tools, the EPA is leading the world in making data about how chemicals cause toxicity publicly available for researchers, industry, and the general public to use. In the past 10 years, the National Center for Computational Toxicology had made data on hundreds of thousands of chemicals publicly available. This means that as the EPA conducts its own research, it spurs more research at our nation’s universities, speeding progress to replace outdated animal tests with more human-relevant methods.

The EPA needs the research being conducted by the Chemical Safety for Sustainability research program and the National Center for Computational Toxicology in order to meet the responsibilities Congress gave it when it passed the Lautenberg Act. We urge EPA Administrator Scott Pruitt to maintain funding for these vital programs in its FY2018 budget to ensure continued protection of public health, the environment, and animals.

 

June 20, 2017   animal testing

 

Physicians Committee Scientist Leads New ‘Canadian Centre for Alternatives to Animal Methods'

From the back of a napkin to reality: The Physicians Committee’s Charu Chandrasekera is set to lead the first Canadian center for the research and validation of alternative methods.

Millions of animals are used each year for studies of fundamental biology and disease, drug development, and toxicity testing. Despite decades of extensive research—often in animals—we still do not fully understand human biology and disease mechanisms. Fully 96 percent of drugs tested to be safe and effective in animals fail in human clinical trials. Therefore, there is an urgent need to transition from animal testing to humane and human-relevant methods to advance human medicine.

Many countries across the globe have already established nonanimal alternatives research and testing centers, and finally Canada joins them. Last week the University of Windsor in Windsor, Ontario, Canada, announced that it has established the first Canadian center dedicated exclusively to human-centered biomedical research and testing, the Canadian Centre for Alternatives to Animal Methods (CCAAM) and its subsidiary, the Canadian Centre for the Validation of Alternative Methods (CCVAM).

The University of Windsor is a comprehensive academic institution located on the Canadian border, across the river from Detroit, Mich. Since 1857, the University has been a progressive and inclusive community that comes together to study, to learn, to teach, and to serve. It places high priority on creativity and collaboration, and respect for ethical social values. CCAAM will contribute to that legacy.

The vision of CCAAM is the replacement of animals in Canadian biomedical research, education, and regulatory testing through 21st century science, innovation, and ethics. CCAAM/CCVAM will develop, validate, adopt, and promote alternatives in Canada through extensive research, academic, and regulatory initiatives in partnership with national and international academic, industry, government, and public sectors, including Health Canada and Environment Canada.

CCAAM plans to establish a state-of-the-art research infrastructure to enable fully humanized research and testing using only human biomaterials and human-based methods. Through in-house, external, and multicenter collaborative efforts, CCAAM will develop research initiatives to study fundamental human biology in health and disease.

CCAAM will develop unique first-in-its-class undergraduate and graduate academic programs in animal replacement science to educate the next generation of scientists, ethicists, and policymakers.

Through these various initiatives at CCAAM/CCVAM, Canada will officially join the global alternatives community and contribute to this field in a uniquely Canadian way.

The Physicians Committee plans to collaborate with CCAAM closely on many fronts to replace the use of animals in research, education, and toxicity testing. The Physicians Committee’s vice president of research policy, Kristie Sullivan, M.P.H., and director of research advocacy, Ryan Merkley, will serve on CCAAM’s advisory council.

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