Global data sharing collaboration identifies opportunities for considerable animal savings in drug safety assessment

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Global data sharing collaboration identifies opportunities for considerable animal savings in drug safety assessment

NC3Rs Press Release, August 20, 2014; reprinted with permission
An international cross-company data sharing initiative has brought together pharmaceutical regulators and industry representatives in an effort to proactively analyse historic practice in the use of recovery animals in toxicology studies, and to identify opportunities to embed improvements. 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 several key recommendations laid out in a paper 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 National Centre for the Replacement, Refinement and Reduction of Animals in Research (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, and all participants in this project were keen to explore ways in which they can improve practice. A thorough review of the literature and consideration of previously gathered information on a similar or related compound should add weight to decisions related to recovery animal use.

The collaborative effort analysed data on 137 compounds from 259 studies. A questionnaire completed by many of the collaborators found that historically there has been 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 any recovery animals at all.

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 investigators should refrain from using recovery animals in early studies and consider their use later in development once more information on the toxicity profile is known. Careful consideration should also be given when deciding on the appropriate species, the range of dose groups that need to be tested, and the size of these groups. Number and size of groups should be kept to a minimum.

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, then the reduction in animal use could be substantial.”

Paper reference: Sewell F, Chapman K, Baldrick P et al. 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 (2014) DOI: 10.1016/j.yrtph.2014.07.018