Exposure considerations in human safety assessment: Report from an EPAA Partners' Forum.

Understanding and estimating the exposure to a substance is one of the fundamental requirements for safe manufacture and use. Many approaches are taken to determine exposure to substances, mainly driven by potential use and regulatory need. There are many opportunities to improve and optimise the use of exposure information for chemical safety. The European Partnership for Alternative Approaches to Animal Testing (EPAA) therefore convened a Partners' Forum (PF) to explore exposure considerations in human safety assessment of industrial products to agree key conclusions for the regulatory acceptance of exposure assessment approaches and priority areas for further research investment. The PF recognised the widescale use of exposure information across industrial sectors with the possibilities of creating synergies between different sectors. Further, the PF acknowledged that the EPAA could make a significant contribution to promote the use of exposure data in human safety assessment, with an aim to address specific regulatory needs. To achieve this, research needs, as well as synergies and areas for potential collaboration across sectors, were identified.

Acceptance of oclacitinib maleate (Apoquel®) chewable tablets in client-owned dogs with allergic and atopic dermatitis.

BACKGROUND: The oral acceptance of oclacitinib maleate (Apoquel®) chewable tablets administered twice daily for 7 days at the labeled dose range of 0.4-0.6 mg/kg was evaluated in 121 dogs treated at ten general practice veterinary clinics in the United States. RESULTS: Dogs that were enrolled in the study were client-owned, ranged from 1 to 14 years of age, weighed 3.7 to 60.7 kg, and required twice daily treatment with Apoquel for allergic or atopic dermatitis for 7 days. One hundred and twenty-one (121) dogs with 1673 total dose administrations successfully completed the study and were included in the data summary. Out of a total number of 1673 administrations, 1533 (91.6%) were accepted voluntarily within 5 min, 134 (8%) were consumed with assistance (with food treats or by pilling) outside of the 5 min offering time and 6 (0.4%) doses were not consumed. The per dose percent acceptance rate for the 14 offered doses showed minimal variation ranging from 89.9 to 93.3%. CONCLUSIONS: Client-owned dogs from the general veterinary patient population that required treatment with oclacitinib found the chewable tablets to be very palatable and no aversion occurred with repeated dosing. Oclacitinib chewable tablets were well tolerated and are a palatable alternative to the film-coated tablet.

European Medicines Agency initiatives and perspectives on pharmacogenomics.

Pharmacogenomics, the study of variations of DNA and RNA characteristics as related to drug response, has become an integral part of drug development and pharmacovigilance, as reflected by the incorporation of pharmacogenomic data in EU product information. In this short review article, we describe recent European Medicines Agency initiatives intended to support further the implementation of pharmacogenomics in drug development and surveillance so that patients and the public can benefit from advances in genomic science and technology.

Critical review on the Environmental Risk Assessment of medicinal products for human use in the centralised procedure.

In this article we analyse the Environmental Risk Assessment (ERA) of 59 medicinal products for human use authorised in the EU through the centralised procedure between 2011 and 2012, to establish whether company submissions are compliant with the European Medicines Agency (EMA) guideline and complete in terms of data and study reports provided. The most frequent questions raised by EU regulatory authorities are described, together with an evaluation of the presence and quality of ERA-related information in published regulatory assessment documents. The results of this review show recent improvement in ERA-related data presented in regulatory assessment documents available to the public while also highlighting a need to develop further guidance on environmental issues in order to assist applicants improve their ERA dossiers and overcome current shortcomings.