title: Challenges of general safety evaluations of biologics compared to small molecule pharmaceuticals in animal models.
abstract: BACKGROUND
  The prediction of human toxicity by employing animal models for nonclinical safety evaluation of pharmaceuticals poses numerous challenges. Each type, biologics, vaccines and small molecules, has unique features, which may impact the ability to effectively assess safety.
  
  
  METHODS
  The importance of taking a case-by-case approach is highlighted in this review of the challenges encountered in general safety evaluations for biologics and vaccines compared to small molecules.
  
  
  RESULTS
  The reader will gain insights in specific issues related to building a successful predictive nonclinical safety program for biologics.
  
  
  CONCLUSIONS
  While there is fair concordance for small molecules, animal models used for the safety evaluation of biologics may have limitations with regard to human relevance. For small molecules, this is commonly because of differences in metabolism profiles or off-target effects. For biologics, which are highly targeted molecules, it may be because of differences in physiological processes or biologic pathways that limit pharmacologic relevance. For vaccines or immunomodulatory biologics, it may be related to the complexities of modeling the human immune system in a nonhuman species. While international guidances are available to govern the nonclinical safety assessment process for human pharmaceuticals (such as ICH M3), in many instances a case-by-case approach is employed for novel agents.
authors: MedImmune LLC, One MedImmune Way, Biologics Safety Assessment, Gaithersburg, MD 20878, USA.
authors: Rakesh
authors: R
authors: Dixit
authors: Laurie A
authors: LA
authors: Iciek
authors: Kathleen
authors: K
authors: McKeever
authors: Patricia Clare
authors: PC
authors: Ryan