The findings of the data sharing exercise not only promise savings in animal numbers, but also in time and money for the drug development industry.
The collaboration between 30 major pharmaceutical companies, contract research organisations and academic institutions, as well as regulators from Europe and the US, has led to a number of key recommendations recently published in Regulatory Toxicology and Pharmacology.
As part of the drug development process, it is important to assess recovery – whether toxic side effects from new drugs persist after treatment or whether they can be reversed – and sometimes companies will use animals to evaluate this, but the recent findings indicate that there may be a better way.
The project, jointly headed by the NC3Rs and the UK Medicines and Healthcare Products Regulatory Agency (MHRA), found that decisions regarding when and if recovery animals are included on repeat dose toxicology studies could be strengthened, including by consideration of existing information on a similar or related compound.
The collaborative effort analysed data on 137 compounds from 259 studies. This demonstrated that there is wide variation in recovery animal use; whilst many companies included recovery animals in all studies and at all dose levels to support Phase 1 clinical trials, there were some companies that did not include recovery animals in any study as their default position.
Dr David Jones from the MHRA said: “Recovery animals are currently used inconsistently across studies and between companies. The MHRA, the EU’s Safety Working Party and the USA’s FDA, therefore, thought it important to have the opportunity for discussions with pharmaceutical industry representatives regarding the utility of recovery animals, to provide further clarity about when these test are necessary and when they are not. The NC3Rs provide an ideal arena in which regulators and industry can meet and discuss such issues.”
If the use of recovery animals is deemed necessary for a particular study, the authors have also provided guidance for experimental design. They recommend that companies should avoid using recovery animals in early studies and consider their use later in development once there is more information on the toxicity profile. Careful consideration should also be given when deciding on the appropriate species, the relevant dose group, and the number of animals used.
Dr Vicky Robinson, Chief Executive of the NC3Rs, said: “This is another great example of industry and regulators working together through partnerships facilitated by the NC3Rs. If, as a result of these findings, recovery animals are only used where they are really needed, and this change is implemented across all drug development pipelines, the reduction in animal use could be substantial.”
Sewell F, Chapman K, Baldrick P et al. (2014). Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials. Regulatory Pharmacology and Toxicology. doi:10.1016/j.yrtph.2014.07.018