biologics

Preclinical Development Programs for Biologics

Biologics are a diverse group of products whose common feature is that they are made using biological methods (which may or may not utilize recombinant DNA technology). They are typically derived from well-characterized cells employing a variety of expression systems (including bacteria, yeast, insect, plant, and mammalian cells) and can be produced using cell cultures or animals (ICH S6(R1) 2011).

Biologics must undergo preclinical testing to define their pharmacologic and toxicologic effects prior to exposure to humans. The specific legal framework for preclinical testing of biologics is provided in compound-specific guidelines:

  • Biologics.……………………………………………….ICH S6(R1), June 2011
  • Gene therapy products……………………………EMA/CHMP/GTWP/125459/2006
  • DNA vaccines…………………………………………EMA/CHMP/308136/2007
  • Cell-based………………………………………………EMA/CHMP/BWP/271475/2016 rev.1/EMA/CHMP/410869/06(human CBMPs)
  • Biosimilars……………………………………………. EMEA/CHMP/BMWP/42832/2005 rev. 1 (monoclonal antibodies, FSH, erythropoietin)

This regulatory framework is based on the diversity of products comprising biologics, whose fundamental inherent differences from small-molecule drugs determine preclinical development program requirements.

biologics

Relevant species

One of the key aspects in the preclinical development of biotechnology-derived pharmaceuticals is the use of relevant and often nontraditional species or the use of animal models of disease in preclinical safety evaluation as many biologics cannot be tested in commonly used animal species for preclinical development of new chemical entities.

Species selection in preclinical development programs for biologics should normally include rodent and nonrodent models when rodent species are considered to provide reliable toxicological information. Nonetheless, in most cases, cross-reactivity of tissue panels will often determine nonhuman primates as the species of choice. Making this selection means justifying the use of this model and including evidence that they express the same receptor/epitome and their binding is typical of what is seen in humans.

 

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