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 through the use of a variety of expression systems (including bacteria, yeast, insect, plant, and mammalian cells) and can be produced using cell cultures, animals (ICH S6 1997).

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 (1997) biotechnology-derived products ICH S6 (A) biotechnology-derived pharmaceuticals.
  • Gene therapy products….. EMA / CHMP / GTWP / 125459 / 2006.
  • DNA vaccines…………….. EMA / CHMP / 308136 / 2007 concept paper.
  • Cell-based…………………. EMA / CHMP / BWP / 271475 / 06 EMA / CHMP / 410869 / 06 (human CBMPs).
  • Biosimilars………………… EMEA / CHMP / BMWP / 4283 / 2 / 2005 rev (draft) > monoclonal antibodies, follicle stimulating hormone, > erythropoietin…

This regulatory framework is based on the diversity of products within biologics, which inherent fundamental differences with small-molecule drugs drive the preclinical development program requirements.



Relevant species

One of the key aspects of the preclinical development of biotechnology-derived pharmaceuticals is the use of relevant and often nontraditional species and the use of animal models of disease in preclinical safety evaluation since many biologics cannot be tested in commonly used animal species for preclinical development of New Chemical Entities.

Species selection for preclinical development program of biologics should normally include rodent and non-rodent models if rodent species are considered to provide reliable toxicological information. Nevertheless, in most cases, cross-reactivity of tissue panels will often determine non-human primates as the species of choice.  This selection must justify the use of this model and include evidence that they express the same receptor/epitome and their binding is typical of what is seen in humans.


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