p.10
Regulatory Constraints in Bioprocess Engineering
Why can't process changes be made without consideration?
Because of their considerable regulatory impact.
p.2
Biotechnology vs. Biochemical Engineering
How does biochemical engineering differ from bioprocess engineering?
Biochemical engineering primarily draws from chemical engineering principles, while bioprocess engineering includes mechanical, electrical, and industrial engineering applications.
p.6
Challenges in Penicillin Production
What was required for the submerged tank process to function properly?
Large volumes of absolutely clean, oil- and dirt-free sterile air.
p.4
Challenges in Penicillin Production
What was the outcome of the initial treatment of a London bobby with penicillin?
The penicillin worked initially, but the supply was exhausted, leading to the patient's relapse and death.
p.9
Good Manufacturing Practices (GMP)
What is the primary concern for bioprocess engineers in the pharmaceutical industry?
The production of a product of consistently high quality to satisfy medical needs.
p.10
Good Manufacturing Practices (GMP)
What are key concepts that do not change in biomanufacturing for pharmaceuticals?
Written documentation, consistency of procedures, consistency of product, and demonstrable measures of product quality, particularly purity and safety.
p.1
Role of Bio-process Engineers
What role do engineers play in the context of genetic engineering?
They convert visions into reality through hard work.
p.1
Collaboration Between Biologists and Engineers
What motivates individuals to participate in the field of genetic engineering?
The desire to contribute to the intellectual revolution and society.
p.7
Challenges in Penicillin Production
What challenges were faced in the production of penicillin?
Challenges in reactor design, product recovery, and purification.
p.3
Collaboration Between Biologists and Engineers
How do the fundamental trainings of biologists and engineers differ?
Biologists focus on experimental tools and qualitative results, while engineers emphasize mathematical theories and quantitative methods.
p.8
Regulatory Constraints in Bioprocess Engineering
What regulatory body must ensure the safety and efficacy of bioprocesses in the U.S.?
The U.S. FDA (Food and Drug Administration).
p.9
Regulatory Constraints in Bioprocess Engineering
What happens if a small process change occurs during drug production?
It may require new clinical trials to test the safety of the resulting product.
p.5
Collaboration Between Biologists and Engineers
What strain of Penicillium was isolated that proved superior for penicillin production?
Penicillium chrysogenum, isolated from a moldy cantaloupe.
p.10
FDA Approval Process for Pharmaceuticals
What does validation mean in the context of the FDA?
It refers to the requirement for confirming that a process meets regulatory standards.
p.4
Historical Context of Penicillin Discovery
What was the impetus for resurrecting the discovery of penicillin?
World War II created a desperate need for antibiotics with minimal side effects and broader applicability.
p.2
Role of Bio-process Engineers
What new opportunities are available for bioprocess engineers?
The ability to determine the complete sequence of genes in an organism offers new opportunities in design and monitoring of bioprocesses.
p.4
Role of Bio-process Engineers
What techniques did Norman Heatley develop for penicillin production?
An assay to monitor penicillin production, a culture technique, and a back-extraction process.
p.4
Collaboration Between Biologists and Engineers
What was necessary to produce large amounts of penicillin?
The development of a production process requiring engineers and life scientists.
p.7
Challenges in Penicillin Production
What was the capacity of the first plant for commercial production of penicillin?
14 tanks each of 7000-gal capacity.
p.3
Collaboration Between Biologists and Engineers
What background do engineers typically possess?
Engineers usually have a strong background in physical and mathematical sciences.
p.7
Challenges in Penicillin Production
How much has the yield of penicillin increased from 1939 to now?
From 0.001 g/l to over 50 g/l of fermentation broth.
p.2
Biotechnology vs. Biochemical Engineering
What is bioengineering?
A broad title that includes work on medical and agricultural systems, involving various types of engineers.
p.6
Challenges in Penicillin Production
What challenges were associated with the submerged tank process?
Mold physiology and tank design and operation.
p.4
Collaboration Between Biologists and Engineers
What role did Norman Heatley play in the development of penicillin?
He produced sufficient material for testing the effectiveness of penicillin.
p.6
Challenges in Penicillin Production
What design feature was crucial for the agitator in the submerged process?
A mechanical seal to prevent the entry of organisms.
p.8
Role of Bio-process Engineers
Why is the penicillin experience significant for bioprocess engineers?
It shaped the mindset of bioprocess engineers.
p.9
Good Manufacturing Practices (GMP)
What does process validation ensure in drug manufacturing?
That a specific process will consistently produce a product meeting predetermined specifications and quality characteristics.
p.3
Role of Bio-process Engineers
What should aspiring bioprocess engineers study further?
Microbiology, biochemistry, cell biology, and advanced biochemical engineering.
p.2
Biotechnology vs. Biochemical Engineering
What does biotechnology usually imply?
The use or development of methods of direct genetic manipulation for socially desirable goals.
p.10
FDA Approval Process for Pharmaceuticals
Why does the FDA approve the process and product together?
To ensure that both the manufacturing process and the final product meet safety and efficacy standards.
p.4
Historical Context of Penicillin Discovery
Who were the key figures in building on Fleming's observations of penicillin?
Howard Florey and Ernst Chain.
p.8
Role of Bio-process Engineers
What concept was born with the advent of modern antibiotics?
The concept of a bio-process engineer.
p.6
Challenges in Penicillin Production
What could contamination by foreign organisms lead to?
Degradation of the product, nutrient consumption, or toxin production.
p.8
Collaboration Between Biologists and Engineers
What must bioprocess engineers continually reexamine?
The prejudices inherited from the penicillin experience.
p.9
Good Manufacturing Practices (GMP)
What is the role of GMP in drug manufacturing?
Ensures the manufacturing facility design, equipment, procedures, and personnel training meet quality standards.
p.9
Good Manufacturing Practices (GMP)
What is the significance of documented procedures in GMP?
They provide assurance that products have the identity, strength, quality, and purity they claim to possess.
p.3
Collaboration Between Biologists and Engineers
What is required for engineers to effectively integrate molecular biology into new processes?
A solid understanding of biology and its experimental tools.
p.10
Good Manufacturing Practices (GMP)
What does GMP stand for?
Good Manufacturing Practices.
p.1
Introduction to Genetic Engineering
What are some potential outcomes of the intellectual revolution in genetic engineering?
New medicines, semisynthetic organs, abundant foods, biological computers, superorganisms for pollution degradation, and various consumer products.
p.2
Biotechnology vs. Biochemical Engineering
What is the emphasis of the book regarding bioprocess engineering?
The application of chemical engineering principles to systems containing biological catalysts, with a focus on biotechnology.
p.7
Challenges in Penicillin Production
What special techniques were developed for penicillin due to its fragile nature?
A combination of pH shifts and rapid liquid-liquid extraction.
p.7
Challenges in Penicillin Production
What was the penicillin production capacity in the U.S. by the end of World War II?
Enough for almost 100,000 patients per year.
p.5
Historical Context of Penicillin Discovery
Which companies were prominent in the early efforts to produce penicillin?
Merck, Pfizer, Squibb, and the USDA Northern Regional Research Laboratory.
p.9
FDA Approval Process for Pharmaceuticals
What is the likelihood of a drug receiving FDA approval after entering human clinical trials?
Only one in ten drugs receives approval.
p.5
Challenges in Penicillin Production
Why was the surface method for penicillin production eventually deemed insufficient?
It had a long growing cycle and was very labor-intensive, not meeting the full need for penicillin.
p.2
Collaboration Between Biologists and Engineers
What is the main challenge in combining the skills of engineers and biologists?
It is not easy to combine the skills of the engineer with those of the biologist.
p.1
Introduction to Genetic Engineering
How has genetic engineering been practiced for thousands of years?
Through selection and breeding.
p.8
Role of Bio-process Engineers
What specialized training did chemical engineers lack before the penicillin process?
Training in the life sciences.
p.1
Biotechnology vs. Biochemical Engineering
Why are biological systems considered predictable?
Because they obey the rules of chemistry and physics.
p.8
Biotechnology vs. Biochemical Engineering
What has not yet emerged from the experience with genetically engineered cells?
A similar paradigm to that established by the penicillin process.
p.3
Collaboration Between Biologists and Engineers
What is a strength of biologists in research?
Biologists excel in forming testable hypotheses, experimental design, and interpreting data from complex systems.
p.7
Collaboration Between Biologists and Engineers
What multidisciplinary approach did Merck take in penicillin production?
Assigned a chemical engineer and microbiologist to each aspect of the problem.
p.7
Collaboration Between Biologists and Engineers
What areas of knowledge contributed to the progress in penicillin fermentation?
Understanding of mold physiology, metabolic pathways, penicillin structure, mutation methods, and process control.
p.9
Good Manufacturing Practices (GMP)
What are SOPs in the context of GMP?
Standard Operating Procedures that document processes and ensure compliance with quality standards.
p.10
Regulatory Constraints in Bioprocess Engineering
What is the role of bioprocess engineers in relation to regulatory requirements?
Much of their effort is to satisfy regulatory requirements.
p.1
Introduction to Genetic Engineering
What has enabled us to manipulate life at its most basic level?
The molecular-level manipulation of DNA.
p.6
Challenges in Penicillin Production
What process did engineers generally favor for antibiotic production?
A submerged tank process.
p.2
Biotechnology vs. Biochemical Engineering
What is the focus of biomolecular engineering?
Research at the interface of biology and chemical engineering, focused at the molecular level.
p.1
Role of Bio-process Engineers
What is the primary job of a bio-process engineer?
To rationally construct processes using living cells on commercial scales.
p.8
Biotechnology vs. Biochemical Engineering
What paradigm was established by the penicillin process?
A paradigm for bio-process development and biochemical engineering.
p.6
Challenges in Penicillin Production
What are important constraints on antibiotic fermenter design?
Oxygen supply and heat removal.
p.4
Challenges in Penicillin Production
Why did Florey and his associates approach pharmaceutical firms in the United States?
To persuade them to develop the capacity to produce penicillin, as the U.S. was not at war at that time.
p.9
FDA Approval Process for Pharmaceuticals
What are the three phases of human clinical trials?
Phase I (safety), Phase II (efficacy and side effects), Phase III (large-scale testing).
p.3
Historical Context of Penicillin Discovery
What significant observation did Fleming make with the contaminated dish?
No bacteria grew near the foreign particle, indicating the presence of an antibacterial agent.
p.3
Historical Context of Penicillin Discovery
What did Fleming demonstrate about the material secreted by the mold?
It had powerful antimicrobial properties.
p.5
Challenges in Penicillin Production
What was the initial method used for penicillin manufacturing?
The surface method, where mold grew on top of a quiescent medium.
p.3
Historical Context of Penicillin Discovery
What was Alexander Fleming trying to isolate in 1928?
The bacterium Staphylococcus aureus.
p.5
Collaboration Between Biologists and Engineers
What significant contribution did the Northern Regional Research Laboratory make to penicillin production?
Development of a corn steep liquor–lactose based medium that increased productivity tenfold.
p.5
Challenges in Penicillin Production
What was the estimated concentration of penicillin in fermentation broth in 1939?
One part per million (ca. 0.001 g/l).
p.5
Challenges in Penicillin Production
What challenge did companies face regarding the fermentation process for penicillin?
Low production rates per unit volume and difficulties in product recovery and purification.
