What is devTOX quickPredict (devTOX^qp)?

The devTOX^qp in vitro assay uses either human embryonic stem (hES) cells or induced pluripotent stem (iPS) cells to provide a signal of a test article’s potential to disrupt human development.

What are the benefits of using the devTOX^qp?

• Early identification and elimination of potential developmental toxicants may help to reduce time and cost of subsequent testing and aid in prioritizing a series of molecules for further development.
• The first and only human cell-based system commercially available for developmental toxicity testing.
• Better predictivity than other in vitro and in vivo assays.
• Low cost.
• Small amount of test compound required.
• Quick turnaround time.

How should the assay be used?

devTOX^qP can be used to screen and prioritize a series of compounds to determine which compound has the lowest developmental toxicity potential. Due to its high concordance with required animal models, devTOX^qP can be used as part of the workflow to reduce animal testing.

During which stage of a compound’s development should the assays be used?

Most often, devTOX is used early in the discovery phase for a series of molecules after they have been deemed active. The devTOX^qP assay can be used to provide information regarding the concentration at which the test article has the potential to elicit developmental toxicity. devTOX^qP aids in decision-making prior to much more costly and time-intensive preclinical in vivo studies.

Why do you offer both hES and iPS cell types?

Stemina offers two cell types to provide flexibility in choosing the cell type that best serves the scientific or regulatory / policy requirements of our clients. The assay was originally developed and optimized using WA09 hES cells. Of the available hES cell lines, this line is best characterized and used most often by researchers. Some sponsors prefer iPS cells due to corporate policies or governmental regulations that preclude the use of hES cells.

Which is more effective: hES or iPS cell types?

Experiments comparing the compound predictions from the devTOX^qP model have shown that both iPS and hES cells predict potential developmental toxicants with 85% accuracy. While slight differences have been identified between these two cell types, the scientific literature and our own internal studies have shown that these differences are minor. Studies performed at Stemina have shown 97% concordance between the cell types.

How do I interpret the results across the eight exposure levels provided by the devTOX^qP assay if I don’t know the likely therapeutic or exposure range early in the discovery phase of development?

The results should be considered in the context of the total information generated as test articles are advanced through testing, just as would be done with any discovery phase in vitro assay. If the test article shows no potential to act as a developmental toxicant, or indications of developmental toxicity are seen only at the highest exposure levels, this is important information as the likely therapeutic or exposure range is established.

Who should be using devTOX^qP?

Any company that is developing new compounds for use in pharmaceutical, agricultural, industrial, tobacco, cosmetic, or consumer products that will have potential for human exposure.

How predictive is devTOX^qp for signaling the potential for developmental toxicity?

The assay is 85% predictive of developmental toxicant across a wide range of more than 100 chemicals. Accuracy may be higher or lower in certain categories of chemicals.

Can devTOX^qp replace other developmental toxicity assays?

Yes. Based on the above benefits, devTOX^qP has proven to be more predictive and less subjective than the zebrafish, whole embryo culture, and mEST assays. The data generated with the devTOX assays presents an excellent opportunity to include an in vitro human endpoint in read-across or weight-of-evidence approaches.

Note: Under the current regulatory requirements, devTOX^qp cannot replace required standard in vivo mammalian studies, but can reduce the number of animals used by eliminating compounds from further testing.

What if a compound elicits a metabolic response at the same concentration where cytotoxicity is observed?

This type of response can be more difficult to interpret and additional data can help put the results into context. In the absence of an additional data, this result can be interpreted as a positive response. If a compound is cytotoxic to hES or iPS cells, it would likely kill the cells in the developing embryo, which could lead to embryo lethality or malformations.

How predictive is the devTOX^qP assay of the outcome in required in vivo tests?

The devTOX^qP assay is 80% concordant with the rodent and rabbit Segment II models for a set of compounds with a broad range of chemotypes.