BSB3503 - Biomanufacturing CHAPTER 3 Biomanufacturing Processes Author: Nurul Azyyati Sabri Co-Author / Editor: Rama Yusvana Faculty Industrial Sciences & Technology yusvana@ump.edu.my

Product Development & Regulatory Milestones Include Preclinical, Clinical, Biologics License Application (BLA), and Non-disclosure Agreement (NDA) Submission International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was formed in 1990 Help biopharmaceutical entities to register and develop safe, quality, and effective drugs Include therapeutic proteins such as monoclonal antibodies, cytokines, etc

Biomanufacturing Product development diagram and regulatory milestones Source: Cytovance Biologics Inc., John Conner, 2013

Mainly by Recombinant DNA technology to produce therapeutic products Biologic products are derived from living systems that may or may not be modified Mainly by Recombinant DNA technology to produce therapeutic products Such as monoclonal antibody, a vaccine, cytokines, enzymes etc 1761—English surgeon Edward Jenner pioneers vaccination, inoculating a child with a viral smallpox vaccine 1928—Scottish scientist Alexander Fleming discovers penicillin 1942—Penicillin is mass produced in microbes for the first time (WW II). 1978—Recombinant human insulin is produced for the first time.

Some are naturally occurred such as whole blood and blood components, organ and tissue transplantations Artificially via Recombinant DNA technology such as “insulin”, monoclonal antibodies, signaling-type proteins, and receptor-type proteins Biologics can be defined as a large complex molecule produced by or extracted from living system such as bacteria or mammalin cells 1761—English surgeon Edward Jenner pioneers vaccination, inoculating a child with a viral smallpox vaccine 1928—Scottish scientist Alexander Fleming discovers penicillin 1942—Penicillin is mass produced in microbes for the first time (WW II). 1978—Recombinant human insulin is produced for the first time.

Typical Biologics manufacturing Process Flow Diagram (PFD)

Typical Biologics manufacturing Process Flow Diagram (PFD) The biomanufacturing process, process controls as well as the complete physiochemical and biological testing all together characterize the biological product Source: Cytovance Biologics Inc., John Conner, 2013

Various Biological products & mechanism of action are shown below T-cells are a type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections. killer T-cells and helper T-cells. Killer T-cells have ‘X-ray vision’ as they are able to see inside our bodies own cells simply by scanning their surface Helper T-cells orchestrate an immune response and play important roles in all arms of immunity TNF – Tumor Necrosis Factor

Downstream Biomanufacturing During the downstream process, impurities are removed from the final end product that will be made available to consumers.

Extracellular Product Cell Extracellular means that the microbes or cells used in the biomanufacturing process secrete or release the product as they grow. The product ends up in the culture medium outside the cell. Product (outside the cell) Cell

Cell Separation The stage of downstream processing where the product is separated from the cells using a filter or centrifuge.

Funnel lined with a coffee filter Filtration Apparatus A set of materials/medium (sand, gravel, paper) and equipment designed to aid in the separation of the cells from the product. Funnel lined with a coffee filter Graduated Cylinder 1 tablespoon of Gravel 2 tablespoons of Sand

Quality Control A system of monitoring the quality of the process by taking samples and testing their concentration and/or activity.

Yield Percentage A mathematical way to calculate how much product was recovered after the filtration process.

Standard Curve A standard curve is a method of plotting data in order to determine the level of product recovery over time.

Concentration Percentage A number based on comparing the color of the filtrate to a known sample or “standard curve.”