In Vivo Exposure Systems and the assessment of Reduced-Risk Products

In the assessment of Reduced-Risk Products (RRPs), in vivo testing cannot be fully replaced by in vitro assays. Indeed, the US Food and Drug Administration draft guidance on RRP applications recommends that non-clinical toxicological studies are conducted and acknowledges the role of non-human in vivo testing as part of this[1]. However, as part of our strategy to “Replace, Reduce and Refine” in vivo testing, we are actively working on new in vitro models in the hope that one day in vitro models could completely replace non-human in vivo assays. 

When in vivo studies are necessary, we use rodents in precise and well controlled inhalation studies. The facility in which we conduct these studies is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) which is testament to the level of care and humane treatment of the rodents that we use. We have a 2-step process to ensure that we are conducting only necessary studies in the most ethical way. Our corporate PMI Animal Welfare Committee reviews all proposed animal studies to evaluate whether study objectives are achievable, or whether the objectives can be achieved through other testing means. We also have an Institutional Animal Care and Use Committee (IACUC), which further evaluates the experimental procedures in detail and makes sure that any opportunity to apply the “Replace, Reduce and Refine” strategy is implemented.

Furthermore, we adhere to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, published by the National Center for the Replacement, Refinement and Reduction of Animals in Research and intended to improve the reporting of research using animals, maximizing information published and thus minimizing the performance of unnecessary studies[2].

Our in vivo exposure systems involve exposing rodents to cigarette smoke or RRP aerosols in one of two ways: whole body exposure or nose-only exposure. Whole body exposure is used for mouse models of human disease while nose-only exposure is used for regulatory inhalation toxicology in rat models.

References: [1] U.S. Food and Drug Administration. Modified risk tobacco product applications: draft guidance. 2012. Available online at: https://www.fda.gov/media/83300/download

[2] Kilkenny, C, et al. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS biology, 2010. 8(6): p. e1000412. Available online at: http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2010;volume=1;issue=2;spage=94;epage=99;aulast=Kilkenny