In Vivo Toxicology and the assessment of Reduced-Risk Products

In vivo toxicology is the study of toxic effects of chemical substances performed within an intact, living organism such as a laboratory animal. 

As a critical part of our non-clinical assessment of RRPs, we conduct in vivo testing to determine in non-human, living organisms whether there is a reduction in the toxic effects of exposure to RRPs aerosols as compared to cigarette smoke. We understand public concerns about using animals in this type of research and as part of our strategy to “Replace, Reduce and Refine” non-human in vivo testing, we are actively working on more relevant in vitro models, in the hope that one day in vitro models could completely replace non-human in vivo assays.  However this will take time and we are not yet in a position to completely remove in vivo testing from our RRP assessment approach.  In addition to this, the US Food and Drug Administration draft guidance on RRP applications recommends that non-clinical toxicological studies are conducted and acknowledges the role of non-human in vivo testing as part of this[1].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” non-human in vivo testing, we are actively working on more relevant 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 PMI Animal Welfare Committee which 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, 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 assays include the 28-day and 90-day inhalation studies performed according to OECD testing guidelines 412 and 413 respectively[3][4].

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

[3] OECD. OECD guideline for the testing of chemicals: subacute inhalation toxicity 28-day study. 2009. [4] OECD. OECD guideline for the testing of chemicals: subchronic inhalation toxicology 90-day study. 2009.