BIOPROCESS ENGINEERING

Part I. Introduction Chapter 1. What is a Bioprocess Engineer?

Textbook: Bioprocess Engineering Basic Concepts 2nd Edition

Administrative Details
Instructor: Assistant Professor Yong Woo Cho, PhD Office: Room # 38-411, The 4th floor, Engineering Building V E-mail: ywcho7@hanyang.ac.kr Tel: (OP) 031-400-5279, (CP) 010-4052-1012 TA: Hwa In Yoon, E-mail: fineyoon@gmail.com, (OP) 4712, (CP) 010-4744-6321 Homepage: http://www.biomedpolym.re.kr Lecture: Monday 4:30 6:00 PM & Tuesday 4:00 5:30 PM Text: Bioprocess Engineering Basic Concepts 2nd Edition (by M. L. Shuler and F. Kargi) 1 Midterm (40%), 1 Final (40%), and Assignments (20%).

Course Outline
Part I. Introduction Chapter 01. What is a Bioprocess Engineer? Part II. The Basics of Biology: An Engineers Perspective Chapter 02. An Overview of Biological Basics Chapter 03. Enzymes Chapter 04. How Cells Work Chapter 05. Major Metabolic Pathways Chapter 06. How Cells Grow Chapter 07. Stoichiometry of Microbial Growth and Product Formation Chapter 08. How Cellular Information Is Altered Midterm Exam Part III. Engineering Principles for Bioprocesses Chapter 09. Bioreactors Chapter 10. Scale-Up and Control of Bioreactors Chapter 11. Recovery and Purification of Products Part IV. Applications to Nonconventional Biological Systems Chapter 15. Tissue Engineering and Gene Therapy Final Exam

The Oldest Protocol for Yeast Production

Bread and Beer Manufacturing Process, the 5th. Dynastry (ca 2400 BC) Leiden Egyptian Museum, Holland

1.1. Introductory Remarks

Biological Revolutions We can now manupulate life at its most basic levelthe genetic. Biological systems are very complex and beautifully constructed, but they obey the rules of chemistry and physics. The Job of the Bioprocess Engineer Engineers should play an essential role in converting biological revolutions into reality The processes to use living cells can be rationally constructed on commercial scale. Close the gaps between chemical engineering and biology

1.2. Biotechnology and Bioprocess Engineering

Researches at the interface of biology and chemical engineering Biotechnology: Genetic manipulation / Applied biology Bioengineering: Engineering with biotechnology Biological Engineering: Emphasis on plants and animals Biochemical Engineering: Emphasis on biological catalysts Biomedical Engineering: Application of engineering principles and techniques to medical fields Biomoleucular Engineering: Focused at the molecular levels Bioprocess Engineering To apply processes based on using living cells or subcomponents of cells Detailed equipment design, sensor development, control algorithms, and manufacturing strategies

We will focus primarily on the application of chemical engineering principles to systems containing biological catalysts, but with an emphasis on those systems making use of biotechnology

1.3. Biologists and Engineers Differ in Their Approach to Research

Biologists Strong with respect to laboratory tools Weak with respect to physics and mathmatics. Engineers Good background in physics and mathmatics. Unfamiliar with exprimental techniques and strategies used by life scientists They are Complementary To convert the promises of molecular biology into new processes to make new products requires their Integration

1.4. The Story of Penicillin: How Biologists and Engineers Work Together
Antibiotics are one of the great marvels of modern medicine

The discovery lay essentially dormant for over a decade

Figure. The mold produces penicillin. The first antibiotic discovered was penicillin, which is made by the common mold Penicillium notatum, shown here growing on bread and in a close-up view. Alexander Fleming discovered penicillin in 1928. He was trying to grow bacteria (Staphylococus aureus), but the pesky mold Penicillium notatum had contaminated his bacterial cultures. Fleming noticed that bacteria did not grow near the mold. Fortunately, he recognized the value of an agent that could inhibit bacterial growth, and the age of antibiotic was born.

Staphylococus Bacteria

Figure. Fungal production of an antibotic. The mold Penicillium produces an antibiotic that inhibits the growth of Staphylococcus bacteria, resulting in the clear area between the mold and the bacteria

Staphylococus Bacteria
They cause boils

Staphylococcus bacteria cling to hairlike appendages called cilia on human skin cells

Penicillin Production by Fermentation

Low rate production per unit volume: 0.001 g/L in 1939 (Gold is more plentiful in see water) Penicillin is a fragile and unstable product Development of a new medium (A corn steep liquor-lactose based medium): increased productivity about tenfold. Better producer strain: Penicillium chrysogenum Superior to hundreds of other isolates A new manufacturing process: A submerged tank process Reactor design Special techniques for product recovery and purification: A combination of pH shifts and rapid liquid-liquid extraction Now, a production rate: 50 g/L

Multidisciplinary Work
This accomplishment required a high level of multidisciplinary work Merck realized that men who understood both engineering and biology were not available. Merck assigned a chemical engineer and microbiologist together to each aspect of the problem. They planned, executed, and analyzed the experimental program jointly, almost as if they were one man Progress has involved better understanding of mold physiology, metabolic pathways, penicillin structure, methods of mutation and selection of mold genetics, process control, and reactor design.

1.5. Bioprocess: Regulatory Constraints

The primary concern is NOT reduction in manufacturing cost, but the production of a product of consistently high quality in amounts to satisfy the medical needs of the population. US FDA From the discovery stage through preclinical testing in animals: 6.5 years Phase I clinical trials: Test safety, about 1 year, 20 to 80 volunteers Phase II clinical trials: Efficacy and side effects, about 2 years, 100 to 300 patients Phase III clinical trials: Efficacy and side effects, about 3 years, 1000 to 3000 patients Data review: 1.5 years Totally 15 years, $400 million Only one in ten drugs that enter human clinical trials receives approval

1.5. Bioprocess: Regulatory Constraints

FDA approval is for the product and the process together Drugs must come from facilities that are certified as GMP (Good Manufacturing Practice) Off-line assays done in laboratories must satisfy GLP (Good Laboratory Practice) Procedures are documeted by SOP (Standard Operating Procedure)

GMP Concerns
The actual manufacturing facility design and layout The equipment and procedures Training of production personnel Control of process inputs (e.g., raw materials and cultures) Handling of products Prevent contamination Dictate flow of material, personnel, and air Procedure validation: include not only operation of equipments but also cleaning and sterilization Key concepts: Written documentation, consistency of procedures, consistency of product, and demonstrable measures of product quality (particularly purity and safety)