1. Biotechnology Products & Regulatory requirements Medical Writer Group NL Naarden, 8 Dec 2005 H.F. Schuring

2. Definition of Biotechnology Bio –deals with living organisms Technology –involves the practical application of knowledge Therefore, Biotechnology is the practical application of knowledge related to living organisms

3. Biotech vs Biologicals Biologicals are products which quality, purity, specificity, and potency cannot be expressed completely by chemical and physical terms (UK approach) Origin, manufacture and structure are not mentioned, therefore includes –immunological products (vaccines, toxins, serum, and allergens -89/342/EC) –products from human blood or plasma - 89/381/EC

4. Wide Range of Products New molecular entities: –Recombinant DNA products CHO products Proteins from milk of transgenic animals –Gene therapy products –Cell therapy products –Monoclonal antibodies

5. Evolution of Biotechnology 10,000 BC: Alcohol fermentation, bread, cheese & yogurt 5,000 BC: Beer is brewed in Egypt

6. Evolution of Biotechnology (Overview) Whole Organism (macroscopic level) Cells and other Microorganisms Subcellular –Components of the cell (organelles) –What did these components do? Nucleus and its Genetic Material –How did this material control the cell? –How was this information passed on as the cell divided?

7. 1953 Watson & Crick resolve the double helix structure of DNA Evolution of Biotechnology 1800 - today

8. Key Developments in Biotechnology Cell Culture (bacteria, yeast, CHO) Monoclonal Antibodies Molecular Biology –Genetic Engineering –Recombinant DNA Technology –Transgenic Animals –Cloning Stem Cells (Great Potential)

9. Commercial Production Level Control Medium Product Base Bioreactor with Packed Bed Addition Harvest Addition

10. Quality Purity - Impurity Biological properties Immunological properties Strength Potency Safety Efficacy

11. Implication of the manufacturing process on a r-DNA biotech product The process defines the product and The process determines the quality and reproducibility Note: case by case assessments

12. Regulatory Requirements Quality, Safety and Efficacy –Less guidance available compared versus NCEs Quality specifics: –Characterization –Viral safety –Cell banking Preclinical specifics: –ICH S6 versus ICH M3 –Immunogenicity Clinical specifics: –dependent on product –Immunogenicity