Agency-wide CRADA agreement also includes studies with Brain-Chip in Alzheimer’s disease, Intestine-Chip in microbiome health, and Liver-Chip in individualized toxicity responses
Emulate announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. Food and Drug Administration (FDA) to enable multiple studies across FDA offices in priority research areas, including programs to evaluate COVID-19 vaccines and understand human immune response against SARS-CoV-2, the virus that causes COVID-19.
Under the CRADA, the FDA will use a range of Organ-Chips from Emulate to study the safety, efficacy, and mechanisms of drugs regulated by the FDA. The initial studies use Organ-Chips—which are able to recreate the natural physiology of specific human tissues and organs—in areas where conventional cell culture and animal-based testing methods have limitations in reflecting human biology and disease mechanisms that are not yet understood, such as Alzheimer’s disease and COVID-19. This new CRADA agreement follows the successful completion of the first Emulate CRADA with the FDA initiated in 2017 that focused on toxicity studies using the Liver-Chip.
“We are excited to continue our relationship and collaborative work with the FDA, combining Emulate’s expertise with researchers at the FDA to explore how our Organ-Chips can lead to new ways to improve standards, understand disease and drug mechanisms, and better evaluate the safety and efficacy of products for human use,” said Jim Corbett, Chief Executive Officer of Emulate. “The FDA is a valued stakeholder and strategic collaborator as our Human Emulation System® continues to be adopted for the evaluation of pharmaceuticals and other products that are reviewed and approved by regulatory authorities to protect and improve human health.”
“The FDA has a long history of supporting efforts to develop new regulatory tools that have the potential to refine, reduce, or replace animal testing,” said FDA Chief Scientist, Rear Admiral Denise Hinton. “Our deep engagement in research collaborations like this one is crucial to advancing technologies like Organ-Chips that may help identify toxicity, efficacy, and disease susceptibility earlier in product development. A robust commitment to science is at the core of our public health mission and helping to facilitate advancements in regulatory science reflects our dedication to fostering the development of critical medical products to address public health threats like COVID-19.”
Covid-19 lung-chip study to advance understanding of protective immunity and vaccine safety
The Lung-Chip study, which will be led by the FDA’s Center for Biologics Evaluation and Research (CBER), aims to address one of the most important questions regarding protective immunity against SARS?CoV-2: why individuals experience a wide spectrum of disease severity and what constitutes a real protection against future infection. The Emulate human Lung-Chip offers the unique functionality of mechanical strain and dynamic fluid flow to recreate the microenvironment found in the human lung. Highlights of the study objectives include:
- The study will infect the Lung-Chip with multiple strains of SARS-CoV-2 and delineate the initial innate immune response toward the virus to explore susceptibility to SARS?CoV-2 infection.
- The study will examine the antibody response in the Lung-Chip generated by human plasma samples containing high titer neutralizing antibodies against SARS-CoV-2, showing how these antibodies may protect human lung cells from viral infection and enable cellular immunity from SARS-CoV-2.
- Knowledge obtained from the study will provide insights into antibody dependent enhancement (ADE), which is relevant to evaluating the safety of vaccines for COVID-19.
“We are enthusiastic to collaborate with essential regulatory partners like the FDA to apply our unique Organ-on-Chips platform to advance the understanding of the SARS-CoV-2 virus and to do our part in bringing safe and effective COVID-19 vaccines and treatments to the world,” Lorna Ewart, PhD, Executive Vice President, Scientific Liaison of Emulate. “There is a time-sensitive need to contribute our technology and expertise to support the FDA with their COVID-19 response, and over time, there will continue to be a need to understand longer-term protective immunity and vaccine safety.”
Studies with multiple organ-chips support areas of emerging disease biology and drug mechanisms
The CRADA is led by the FDA’s Office of the Chief Scientist, allowing for studies across FDA offices with Organ-Chips from Emulate. Through the CRADA, multiple installations of the Human Emulation System will be established in several FDA laboratories.
In addition to the COVID-19 study, other projects that will be initiated under the CRADA include:
- Brain-Chip to model Alzheimer’s disease using patient-derived induced pluripotent stem cells: Using cells from Alzheimer’s patients, these induced pluripotent stem cells (iPSCs) will be differentiated into several types of brain cells in order to model and measure characteristics of Alzheimer’s disease and later study potential toxicities and beneficial effects of treatments for this disease.
- Intestine-Chip to study effects on the human intestinal microbiome and resistance development: This study will use the Emulate Intestine-Chip, which overcomes limitations of currently available cell culture and animal-based testing methods to model human intestinal physiology and microbial complexity, to determine the impact from drug residues in animal derived foods on bacterial colonization and antimicrobial resistant bacteria in the human microbiome.
- Liver-Chip to predict patient susceptibility and adaptation to drug-induced liver toxicity: Liver cells from different donors will be cultured in the Liver-Chip to assess if toxicity responses are transient and/or patient-dependent, and to identify liver-specific markers that help distinguish patients highly-susceptible to liver toxicity – which is a side effect of various types of medicines commonly observed in susceptible patients.