1. The document discusses trends and perspectives in modern pharmaceutical biotechnology, including the development from traditional biotechnology using secondary metabolites to modern biotechnology using recombinant DNA techniques.
2. It describes the transition from first generation biopharmaceuticals that mimic natural proteins to second generation biopharmaceuticals with improved properties through techniques like PEGylation, protein engineering, and protein fusions.
3. The introduction of biosimilars, advances in gene therapy and tissue engineering, and progress toward personalized drug therapy are also discussed as important trends and future perspectives in the field.
Future trends and perspectives in modern pharmaceutical biotechnology
1. FUTURE TRENDS AND PERSPECTIVES IN MODERN PHARMACEUTICAL BIOTECHNOLOGY Prof. Borut Štruk elj Faculty of Pharmacy, UL, Slovenia BWP, EMEA London Ph. Eur. Strasbourg
3. What is a modern pharmaceutical biotechnology? keyword: “ PHARMACEUTICAL BIOTECHNOLOGY” GOOGLE 1996: app. 35.000 hits GOOGLE 2006: app: 3.220.000 hits ! Pharmaceutical biotechnology: the use of living things or parts in order to create or modify drugs Modern pharmaceutical biotechnology: the use of living things or parts by means of recombinant DNA technology in order to create or modify drugs and physiological targets
4. From the starting point of protein pharmaceuticals…. 100 Years ago Serum Therapy 1893 Emil von Behring immunizing a “ serum-horse”
8. Biopharmaceuticals or protein drugs have proven to be safe and effective therapies in many disease indications The 1 st generation biopharmaceuticals Replacement therapies (mimic the normal function of a protein) “ Antagonist” therapies (in which protein function is inhibited - usually antibodies) Many successful products: Erythropoietin, insulin, human growth hormon (HGH), interferons (IFNs), granulocyte colony-stimulating factor (G-CSF), etc.
14. 2nd Generation Biopharmaceuticals: Transforming Proteins into Protein Drugs with Improved Properties Post-production modification derivatization, conjugation (PEGylation , polysialylation, HESylation, fatty acid group derivatization) Amino acid engineering From single mutations to large scale modifications (chimeric or humanized mAbs), introduction/removal of glycosylation sites, introduction/removal of cysteines, introduction of unnatural amino acids, alteration of protease sensitive regions, removal of agretopes to reduce immunogenicity, removal of deamidation-prone Asn, substitution of expoased non-polar amino acids, etc. Protein-protein fusions (IgG, IgG1 Fc, albumin, transferrin, Hsp 65, antibodies or their fragments) New drug delivery systems (liposomes, nanoparticles, microparticles)
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16. Future trends : app 500 biotech drugs in clinical trials in 2007 480 are protein-based, 11 gene therapy, 14 antisense DNA or RNAi-based products
20. Proteins vs SCE: complexity Size Structure Modification Stability Epoetin Aspirin Denaturation, Aggregation, Degradation, Oxidation, ... Glycosylation, Acylation, etc.
21. IgG Antibody ~ 25,000 atoms Aspirin 21 atoms hGH ~ 3000 atoms Large Biologic Small Molecule Drug Large Molecule Drug Car ~ 3000 lbs F16 Jet ~ 25,000 lbs (without fuel) Bike ~ 20 lbs Proteins: Size, Structure & Complexity Complexity Size Source: Genentech
22. Manufacturing of recombinant Proteins is a complex p rocess DNA Vector Cloning into DNA Vector Large-scale Fermentation Downstreaming Transfer into Host Cell, Expression, Screening/Selection e.g., bacterial or mammalian cell Formulation
23. Biosimilars Manufacturers: Different Process – different Product Maybe the same genetic sequence (Probably) a different DNA vector A different recombinant cell expression system A different fermentation process A different downstreaming protocol Different in-process controls Maybe a different formulation A second manufacturer uses... DNA Vector Cloning into DNA Vector Large-Scale Fermentation Downstreaming Formulation Transfer into Host Cell, Expression e.g., bacterial or mammalian cell
