Production of Biopharmaceuticals PDF

 They are proteins (including antibodies), nucleic acids (DNA, RNA or antisense oligonucleotides) used for therapeutic or in vivo diagnostic purposes, and are produced by means other than direct extraction from a native (non-engineered) biological source. The first such substance approved for the...

 They are proteins (including antibodies), nucleic acids (DNA, RNA or antisense oligonucleotides) used for therapeutic or in vivo diagnostic purposes, and are produced by means other than direct extraction from a native (non-engineered) biological source. The first such substance approved for therapeutic use was recombinant human insulin.  Some Important BiopharmaceuI tical products that are available: Insulin Interferon FactorVIII Streptokinin Beta-endorphins Production of biopharmaceuticals Steps in the production of biopharmaceuticals Production of biopharmaceuticals Identify gene of interest Develop host cell Establish cell bank Protein production Purification Analysis Formulation Storage and Handling Fig: How Biopharmaceuticals are produced?   Select a vector to carry the gene Insert the gene into the genome of a host (a suitable bacterial or eukaryotic cell) The exact DNA sequence and the type of host cell used will significantly influence the characteristics of the product 7  A cell bank is then established, using an iterative and elaborate cell screening and selection process, yielding a unique master cell bank. No two master cell banks are exactly alike. 8  The conditions under which cells are cultured can affect the nature of the end product.( 9 5. Purification Any change in the purification process can affect the clinical characteristics of the product. 10  Protein molecules are analyzed for uniformity in terms of structure and potency. A wide variety of analytical tools are used to examine: 3D structure/Aggregation/Isoform profile(a These tests remain limited in their ability to detect all product characteristics that may affect clinical efficacy and safety. 11  Formulation is a key step in stabilizing the protein. The components of the formulation, and the process used, can significantly affect the product’s behavior in patients. 12  Biopharmaceuticals are very sensitive to temperature changes and/or shaking. Strict storage and handling conditions are therefore essential for maintaining product integrity and stability. Poor adherence to (cold) storage requirements can affect clinical efficacy and safety. 13                 – – – Tubular bowl Chamber DISC    – – –  – – + + + + + + - + + + - + + + - + +- - + + - + + Net negatively Positively charged Protein binds to charged (cationic) (anionic) ion matrix protein at selected exchange matrix pH   – – –  – – – –  Enzyme Affinity ligand + Matrix Spacer arm Active-site-bound enzyme 2. Immunoaffinity chromatography Protein epitope Antibody Ligand + Matrix Spacerarm Antibody bound enzyme   Large protein Small protein GPC in operation  μm