Bio process engineering chapter 1 (1)-1.pptx

bio process engineering

1. What is Bio chemical Engineer ing ?

2. Biological systems are very complex and beautifully constructed, but they obey the rules of chemistry and physics. So, we can do engineering analysis on them. Living cells are predictable, and the processes to use them can be rationally constructed on commercial scales. Biological Systems

3. Biotechnology Biotechnology usually implies the use or development of methods of direct genetic manipulation for a socially desirable goal. Such goals might be the production of a particular chemical, but they may also involve the production of better plants or seeds, or gene therapy, or the use of specially designed organisms to degrade wastes The key element for many workers is the use of sophisticated techniques outside the cell for genetic manipulation. Bioengineering is a broad title and would include work on medical and agricultural systems. its practitioners include agricultural, electrical, mechanical, industrial, environmental and chemical engineers, and others. Bioengineering

4. Biochemical Engineering Biochemical engineering has usually meant the extension of chemical engineering principles to systems using a biological catalyst to bring about desired chemical transformations. But is it limited to biocatalysts only? Biochemical engineers translate exciting discoveries in life sciences into practical materials and processes using biology to make products we all need, such as medicines and fuels.

5. Biochemical engineers are key players in the greatest biomedical challenges that lie ahead including: can we make medicines more cheaply and quickly how to make food more efficiently and with less energy are there ways to make biofuels and new materials that don’t rely on oil as a raw material? how do we take innovative healthcare products, such as stem cells and gene therapy, from discovery to being widely available? 5

6. What do biochemical engineers do? Biochemical engineers design ways of getting cells to do make or do what they need them to, and then to obtain the product in a way that is useful. The cells could be from animals, bacteria or single-celled algae, each type needs to be treated in a different way to get them to do what is needed. Taking the manufacture of a vaccine as an example, here are some of the questions we need to answer:  how can we grow the cells how do we keep them alive how can we get them to make the vaccine what’s the best way to the vaccine out of the cells how can we separate what we want from what we don’t can we do all this safely, efficiently and cheaply enough for people to afford it Without the answers to these questions, the vaccine isn’t a viable medicine as it could be too expensive to make, not work properly or take too long to reach people. 6

7. Bio Engineering Biochemical engineering has usually meant the extension of chemical engineering principles to systems using a biological catalyst to bring about desired chemical transformations. Biomedical engineering has been considered to be totally separate from biochemical engineering, although the boundary between the two is increasingly vague, particularly in the areas of cell surface receptors and animal cell culture. In fact the definitions of biochemical, bioprocess engineering and synthetic biology is close to each other and have some difference in their working domain and can be called subsets of bioengineering

8. It is in fact drawing its principles from branch of science that encompasses a broad range of methodologies from various disciplines, such as  biotechnology ,  biomaterials ,  material science/engineering ,  genetic engineering ,  molecular biology ,  molecular engineering ,  systems biology ,  membrane science ,  biophysics ,  chemical and biological engineering ,  electrical and computer engineering ,  control engineering  and  evolutionary biology . Interdisciplinary nature of Biochemical Engineering

9. Difference between Biologists and Engineers In the development of knowledge in the life sciences, unlike chemistry and physics, mathematical theories and quantitative methods have played a secondary role. Most progress has been due to improvements in experimental tools. Results are qualitative and descriptive models are formulated and tested. Consequently, biologists often have incomplete backgrounds in mathematics but are very strong with respect to laboratory tools and, more importantly, with respect to the interpretation of laboratory data from complex systems. Engineers usually possess a very good background in the physical and mathematical sciences. Often a theory leads to mathematical formulations, and the validity of the theory is tested by comparing predicted responses to those in experiments. Quantitative models and approaches, even to complex systems, are strengths.

10. Difference between Biologists and Engineers Biologists are usually better at the formation of testable hypotheses, experimental design, and data interpretation from complex systems. Engineers are typically unfamiliar with the experimental techniques and strategies used by life scientists. The skills of the engineer and life scientist are complementary. To convert the promises of molecular biology into new processes to make new products requires the integration of these skills. To function at this level, the engineer needs a solid understanding of biology and its experimental tools.

11. Story of Penicillin The story of discovery and large scale production of penicillin is directly interrelated with the emergence of bioprocess engineering as a engineering field. In September 1928, Alexander Fleming at St. Mary’s Hospital in London was trying to isolate the bacterium, Staphylococcus aureus, which causes boils. The technique in use was to grow the bacterium on the surface of a nutrient solution. One of the dishes had been contaminated inadvertently with a foreign particle. Normally, such a contaminated plate would be tossed out. However, Fleming noticed that no bacteria grew near the invading substance. Fleming recognized that the cell killing must be due to an antibacterial agent. He recovered the foreign particle and found that it was a common mold of the Penicillium genus

12. Fleming nurtured the mold to grow and, using the crude extraction methods then available, managed to obtain a tiny quantity of secreted material. He then demonstrated that this material had powerful antimicrobial properties and named the product penicillin. The discovery lay essentially dormant for over a decade. During World War II, an antibiotic with minimal side effects and broader applicability was desperately needed and Sulfa drugs have a rather restricted range of activity. Howard Florey and Ernst Chain of Oxford decided to build the antibiotic on Fleming’s observations. Norman Heatley played the key role in producing sufficient material for Chain and Florey to test the effectiveness of penicillin. Heatley, trained as a biochemist, performed as a bioprocess /biochemical engineer. He developed an assay to monitor the amount of penicillin made so as to determine the kinetics of the fermentation, developed a culture technique that could be implemented easily, and devised a novel back-extraction process to recover the very delicate product. After months of immense effort, they produced enough penicillin to treat some laboratory animals.

13. Eighteen months after starting on the project, they began to treat a patient for a blood infection. The penicillin worked wonders initially and brought the patient to the point of recovery. Most unfortunately, the supply of penicillin was exhausted and the patient relapsed and died. Nonetheless, Florey and Chain had demonstrated the great potential for penicillin, if it could be made in sufficient amount. To make large amounts of penicillin would require a process, and for such a process development, engineers would be needed, in addition to microbial physiologists and other life scientists. The war further complicated the situation. Great Britain’s industrial facilities were already totally devoted to the war. Florey and his associates approached pharmaceutical firms in the United States to persuade them to develop the capacity to produce penicillin, since the United States was not at war at that time. Many companies and government laboratories, assisted by many universities, took up the challenge. Particularly prominent were Merck, Pfizer, Squibb, and the USDA Northern Regional Research Laboratory in Peoria, Illinois.

14. The fermentation process was used till then to prepare penicillin. But, there are problem associated with fermentation. These were: - a valuable product made at very low levels. The low rate of production per unit volume would necessitate very large and inefficient reactors, and the low concentration (titer) made product recovery and purification very difficult. In 1939 the final concentration in a typical penicillin fermentation broth was one part per million (ca. 0.001 g/l). - penicillin is a fragile and unstable product, which places significant constraints on the approaches used for recovery and purification. Consequently, many companies were at first reluctant to commit to the fermentation process, beyond the pilot-plant stage. It was thought that the pilot-plant fermentation system could produce sufficient penicillin to meet the needs of clinical testing, but large-scale production would soon be done by chemical synthesis. But the chemical synthesis of penicillin proved to be exceedingly difficult. So, In the end, fermentation route was chosen. There were many difficulties faced by the companies in large scale production of penicillin as it was the first time a bioprocess is used for large scale production of any medicine.

15. There were many challenges in selection of the medium for production of raw material, reactor design, manufacturing process. there were similar hurdles in product recovery and purification. The very fragile nature of penicillin required the development of special techniques. Soon processes using tanks of about 10,000 gal were built. Pfizer completed in less than six months the first plant for commercial production of penicillin by submerged fermentation. By a combination of good luck and hard work, the United States had the capacity by the end of World War II to produce enough penicillin for almost 100,000 patients per year. 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”

16. Progress with penicillin fermentation has continued, as has the need for the interaction of biologists and engineers. From 1939 to now, the yield of penicillin has gone from 0.001 g/l to over 50 g/l of fermentation broth. 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. Before the penicillin process, almost no chemical engineers sought specialized training in the life sciences. With the advent of modern antibiotics, the concept of a bioprocess engineer was born.

17. BIOPROCESSES: REGULATORY CONSTRAINTS For bioprocess engineers working in the pharmaceutical or biotechnology industry the primary concern is not reduction of manufacturing cost, but the production of a product of consistently high quality in amounts to satisfy the medical needs of the population. It is very difficult to get an approval for a drug discovery by FDA ( Food And Drug Administration). . The whole drug discovery-through-approval process takes 15 years on the average and costs about $400 million (in 1996). Only one in ten drugs that enter human clinical trials receives approval. This process greatly affects a bioprocess engineer. FDA approval is for the product and the process together. There have been tragic cases, where a small mistake or flaw caused the FDA disapproval and whole process has to be started again.