Tools for PCR amplification of DNA

Growing in vitro toxicity test market catches investor attention

Increased demand for non-animal chemical safety evaluations and for greater efficiency in testing has led to a burgeoning new market for in vitro and in silico methods, and financial investment research companies are beginning to take notice.

In January, a report by BCC Research estimated that the combined in vitro/in silico test market – valued at $4 BILLION (USD) in 2011 and $4.9 BILLION in 2012 – will reach $9.9 BILLION in 2017.  The report also discusses the potential for continued growth in the market; quoted in one news release, report author Robert Johnson noted, “Our research indicates that the current wave of in vitro adoption globally will take at least five to seven years, and it could be decades before animal testing is replaced entirely.”

In April, Markets and Markets projected a market of $17,227 MILLION by 2018 (though this report seems not to include in silico tests). According to this analysis, “Europe was the largest contributor to the global in vitro toxicology testing market in 2013. It will also be the fastest growing region till 2018. The European market is witnessing growth as a result of strong government directives to altogether stop animal testing and replace in vivo testing by in vitro methods. The Asian countries…are also expected to register double-digit growth from 2013 to 2018 due to the low costs offered by the developing nations to conduct studies.”

In October, an analysis by Persistence Market Research reinforced these broad patterns (note that dollar figures are not provided in the summary available to the public).  The report notes that the market drivers are slightly different for the pharmaceutical and cosmetics industries: in pharmaceuticals, there is a growing trend “towards detecting the toxicity during initial stages of production,” while for cosmetics “support from regulatory authorities for using in-vitro and in-silico methods for studying toxicity of a substance is driving the in-vitro toxicity testing market…”  Persistence Market Research is also tracking growth in industry use of microfluidics: the market is projected to increase from $1,531.2 MILLION (USD) in 2013, to $5,246.4 MILLION in 2019, with Asia experiencing the highest growth. Microfluidic devices (such as the organs-on-chips being developed by the Wyss Institute, and 3-dimensional cell “co-cultures” such as those produced by Hepregen and HuRel) are increasingly used by pharmaceutical companies in their drug development and safety screening process, and are used in other health and manufacturing industries, as well.

For the purposes of predicting human responses to chemicals, non-animal test methods are proving to be as good as or better than the animal tests they are intended to replace. In addition, in vitro methods exponentially reduce the cost and time involved in identifying and safety- testing potential new pharmaceutical compounds.  This is no small matter; a recent study by the Tufts Center for the Study of Drug Development reports that it costs $2.6 BILLION (USD) to bring a new drug to market. Government initiatives to profile tens of thousands of already-marketed household and industrial chemicals stand to gain from improved speed and cost effectiveness, as well, and are among the key market drivers identified by these reports – along with regulatory activities such as REACH, and increasing public concerns about the ethics of animal research.

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Male thyroid anatomy

Paper encouraging non-animal approaches to metabolism wins award

Among the awards bestowed at the 9th World Congress for Alternatives and Animal Use in the Life Sciences in August, a paper co-authored by consortium director Catherine Willett was named the journal ALTEX’s “Best ALTEX article of 2013.”

In vitro Metabolism and Bioavailability Tests for Endocrine Active Substances: What is Needed Next for Regulatory Purposes?” by Miriam N. Jacobs, Susan C. Laws, Kate Willett, Pat Schmieder, Jenny Odum, and Toine F. Bovee, revisits and expands on recommendations put forth in a 2008 OECD review paper that argued for the assessment of human metabolism in in vitro assays used to screen endocrine-active substances.  Although that earlier paper showed that many of the necessary screening tools were already available, little progress has been made by the European, US, or Japanese validation agencies toward validating such methods for use in a regulatory context.  In the ALTEX paper, Jacobs et al. outline a series of projects designed to accelerate validation, continue to expand the number of available metabolism-enhanced screening assays, and improve and expand predictive tools.


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john wikswo_neurovascular unit on a chip

NIH announces funding for the next phase of its Tissue Chip for Drug Screening program

This week, the National Institutes of Health (NIH) announced funding for the next phase of its Tissue Chip for Drug Screening program. In this phase, $17 million will be distributed to 11 projects that will refine and integrate existing 3-D human tissue chips (developed in the first phase of the program) into a system that mimics the physiology of the human body.  The resulting “human body-on-a-chip” will be used to predict the toxicity of potential drugs or other biological agents, ultimately with much greater relevance, accuracy, and efficiency than is possible with traditional animal test procedures.  From the NIH press release:

“The development of tissue chips is a remarkable marriage of biology and engineering, and has the potential to transform preclinical testing of candidate treatments, providing valuable tools for biomedical research,” said NIH Director Francis S. Collins, M.D., Ph.D.

Among the projects funded are a neurovascular-unit-on-a-chip (Vanderbilt), a female reproductive tract system (Northwestern University), a micro-physiological model of metastasis (MIT), and a human cardio-pulmonary-system-on-a-chip (Harvard University).  Read more about these and seven other projects here.

The Tissue Chip for Drug Screening program is a collaboration between NIH, the Defense Advanced Research Projects Agency (DARPA) and the US Food and Drug Administration (FDA), coordinated by the National Center for Advancing Translational Sciences (NCATS).

For a deeper dive into the potential of microphysiological systems, see the September 2014 issue of Experimental Biology and Medicine, especially the opening article by John Wikswo, “The relevance and potential roles of microphysiological systems in biology and medicine” (open access).

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Biochemical laboratory

“Ushering In a New Generation of Chemical Screening”

ToxCast-Robotic-ArmOn the EPA’s “Science” blog, Dr. Richard Judson explains how the agency is using automated chemical screening processes in its Endocrine Disruptor Screening Program:

Ushering In a New Generation of Chemical Screening | Science.




Photo: National Center for Advancing Translational Sciences (NCATS) ultra-high-throughput robotic screening system

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Tools for PCR amplification of DNA

US government program makes progress in non-animal toxicity testing

In the United States, the process of validating methods that reduce, refine or replace the use of animals in safety testing is coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Established by Congress in 2000, the committee consists of representatives from each of the 15 federal regulatory and research agencies that “develops, or employs tests or test data using animals, or regulates on the basis of the use of animals in toxicity testing.”

ICCVAM just released its biennial progress report (covering 2012-2013), which includes summaries of its safety testing activities and its collaborations with other federal and international agencies and organizations.  Among the highlights:

  • The Committee moved two non-animal eye irritation testing methods closer to approval for regulatory use: “OptiSafe” will undergo a formal validation procedure managed by the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) which provides scientific support to ICCVAM; and the Kao Corporation submitted NICEATM’s test results on its Short Time Exposure test (STE) to the Organization for Economic Co-operation and Development (OECD) for formal validation.  (The OECD establishes chemical testing guidelines used by industries in the European Union).
  • Representatives of NICEATM and ICCVAM served on the management team for two EURL ECVAM validation studies: one using HepaRG (a human liver cell line) in an in vitro assay for liver toxicity, and another that validated and formally recommended (to the OECD) the direct peptide reactivity assay, an in vitro skin sensitization test.
  • ICCVAM helped to coordinate two international workshops aimed at reducing or replacing animal tests for vaccine development.
  • ICCVAM scientists collaborated with scientists from Procter & Gamble to develop open source software facilitates an integrated testing strategy that combines existing data from in vitro tests, chemical structure information, and computational models to predict the potency of a skin sensitizer; this information can be used to classify sensitization hazard without additional animal testing.
  • ICCVAM coordinated an international validation study of an in vitro method for detecting estrogenic activity, and began compiling an endocrine disruptor database of “high quality in vivo data” on 52 chemicals selected by the EPA; this can be used for validating in vitro methods.
  • With the FDA, ICCVAM developed industry guidelines on pyrogen testing and photosafety testing that highlight available in vitro methods and strategies for reducing animal use.

The report also summarizes inter-agency activities that support the development of alternative methods, such as “crowd-sourcing” data analysis and modeling through data challenges, and ICCVAM’s participation in international efforts to harmonize test guidelines and regulations.

For more information about ICCVAM and NICEATM, see their web site.

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Unilever’s pathway-based, non-animal approaches to toxicity testing

A new article by scientists at Unilever, a corporate member of the HTPC, describes several areas of safety science in which they are using a pathway-based approach to replace traditional animal tests with a combination of human cell-based in vitro assays and computational models.  The article, “Toxicity testing – non-animal approaches and safety science” (by Fiona Reynolds, Carl Westmoreland and Julia Fentem) is included in the current issue of The Biochemist: “Replacement in Research” (Vol. 36(3), June 2014).

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