From my own first-hand experience, the pharmaceutical industry has invested and continues to invest massively in replacing animal testing. Indeed, there are many publications describing these efforts and many of these have driven changes in practice. But despite this, it would seem that much of this effort has gone unnoticed in the outside world.
In an attempt to bring more light and less heat to the debate, I recently led a project with my Servier colleague Richard Weaver and the Association of the British Pharmaceutical Industry (ABPI) Nonclinical and Biological Discovery Expert Network (NaBDEN) to conduct an analysis of the use of in vitro (including in silico) techniques in preclinical safety testing by the pharmaceutical industry between 1980 and 2013. Expert input from an ABPI intern Jen-Yin Goh and from ABPI staff Nicola Platt and Libby Dixon helped to turn this project into a publication (Goh et al, Toxicology Research, 2015, 4, 1297-1307).
Data were collected from ABPI NaBDEN member companies via a survey which requested the number of compounds screened using in vitro and in silico tests at 5-year intervals between 1980 and 2005 then yearly from 2008 onwards. Four pharmaceutical companies and 3 contract research organizations (CROs) responded to the survey, providing >895000 data points across all years and all assays.
The data showed a steady increase in the use of in vitro testing between 1980 and 2013; indeed >20% of all in vitro tests reported were conducted in the last year of the survey window (2013) and >70% of all in vitro tests reported were conducted since 2010. Use of in vitro tests peaked at >190000 tests per annum in 2012.
Trends and step changes in uptake of in vitro testing were most notable in the three main areas of ADME, safety pharmacology and genotoxicity. This is probably explained by the timing of the adoption of the relevant International Committee on Harmonisation (ICH) guidelines. The pharmaceutical industry has played a key role here, collaborating with academia and regulatory bodies as well as generating several publications and position papers in support of the developing guidelines.
Trends in the uptake of in vitro methods may also be explained by perceptions of utility where scores varied from poor for Eye Irritation (Flourescein leakage) to excellent for Genotoxicity (Ames) and Skin irritation (EpiSkin/Epiderm).
In summary, the data show a large increase and a continuing upwards trend in development and adoption of in vitro alternatives to animal testing in pharmaceutical drug development that provides new opportunities for improved success rates coupled with a strong commitment to the 3Rs. Sharing of these data via publication goes at least some way to illustrate the massive investments made by Pharmaceutical companies and CROs.
But there is more to be done – as we plan to invest in future research aimed at even more replacement of animals in testing, we must learn from the past and critically assess what worked and more importantly what didn’t. Why did some assays have low scores on utility? Why are some assays with high scores not so widely used? Perhaps one of our expert toxicology journals could feature ‘Failed in vitro tests – lessons learned’ – might not be very exciting but it could be very helpful.