9. Specifics of non-clinical development for biological medicines

Biological medicines (or simply biologics) are complex in comparison with small molecules. Biologics are for example large molecules, tissues, cells, or proteins whereas most small molecule medicines are chemically synthesised. The test principles for both drug types are the same but the non-clinical development plan for biologics follows a case-by-case approach.

It should take into account that:
  • Biologics are often highly species specific, e.g. their pharmacological activity may only be shown in non-human primates (NHP). Also, standard species for toxicity testing may not be relevant.
  • Biologics have a strong immunological response. Therefore, there is often no scientific reason to do long-term studies over several months.
  • Biologics are usually immunogenic. Immunogenicity assessment can therefore help researchers interpret the animal toxicology data (not done to predict immunogenicity in humans).
  • The probable dose level leading to a minimal anticipated biological effect (MABEL) in humans needs to be determined.

Standard development plans start to appear for biologics and are different from those well established for small molecules. These plans are driven by lessons learned from past experience and new regulatory guidance.