Key:

MBE 300-F Level: Typically taken first year (Fall Semester)
MBE 300-S Level: Typically taken first year (Spring Semester)
MBE 300-O Level: Typically taken first year (Options -Summer Semester)
MBE 400-F Level: Typically taken second year (Fall Semester)
MBE 400-S Level: Typically taken second year (Spring Semester)

“Science track”: Students coming to the program with an engineering degree will normally take these courses:

MEB 300-F Bioprocess Engineering Principles

The primary goal of this course is to teach the principles of bioprocess engineering in a way that is accessible to biological scientists, bioengineers, and others who have little or no background in chemical engineering.

The course will: Define bioprocessing – Challenges and opportunities for bioprocessing in the 21st century; Describe and develop basic process flow diagram and flow sheet; Differentiate between upstream and downstream processing; Identify key unit operations in upstream and downstream processes; Identify major items of bioprocessing equipment and their function(s) in in a biomanufacturing setting; Establish differences in protein production using bacteria, yeast, animal, and plant cells; Describe key principles involved in bioreactor design and operation; Compare and contrast batch, fed-batch and continuous modes of bioreactor operation; Discuss scale-up of bioreactors and criteria to consider in bioreactor scale-up; Describe factors that impact cell growth and metabolism; Discuss the importance of monitoring culture pH, oxygen, temperature and major metabolites in bioreactors; Discuss primary recovery and some of the ways in which protein products are harvested; Describe downstream processes and some of the key unit operations for purification; Describe the importance of viral clearance and inactivation in purified protein products; Describe Buffer exchange and concentration operation using tangential flow filtration; Describe the formulation of purified protein products; Describe the term biosimilars and discuss the development and regulation of biosimilars.

MEB302-F Principle of Bioreaction Engineering

Introduction to (bio) reaction engineering. Definition of terms, classification of (bio)reactions , kinetics of reaction, rate and order of reaction, methods of determination of the order and rate of reaction. Arrhenius equation. (Bio) Reactor design and performance. Types or reactors. Batch reactors, semi-batch and continuous (perfusion) bioreactors. Mixed flow and plug flow. Calculation and comparison of performance and reactor size. Residence time distributions; E, F and C curves and their application. Methods of measurements of RTD. Models of non-ideal flow, dispersion model and dispersion coefficient, closed and open vessels. Tank in series model and laminar flow models. Bioreactor integration into the process. Process considerations – reaction medium (media composition) – product recovery (yield and titre). Process design methodology. Biopharmaceutical industry examples and case studies. Bioreactor control and operation.

MEB 303-F Molecular Basis of Disease

The list of diseases with known molecular basis includes infectious diseases, cancers, metabolic diseases and mental health diseases. The idea that some diseases are due to genetic causes, a demonstration of which dates back to the early 20th Century, has now been expanded to include the possibility that all recognized human disorders may involve one or more genetic components of the patient. This course examines the role of genes, proteins and RNA in causing or combating diseases, and emphasizes the current conceptual and analytical tools that are brought to bear, and their limitations, on our understanding.

MEB304-F Molecular Biology and Biotechnology

Students will be exposed to the conceptual foundations of biotechnology and the role played by discoveries and applications of molecular biology principles in advancing biotechnology horizons. This is a case-based course in which students will read landmark original papers and patents that shaped biotechnology, and discuss these in the class. The case-based approach will follow the first few weeks of background material where a more standard lecture style will be used so as to bring students with different backgrounds en par with modern molecular biology.

MEB305-F Drug Development

This course is designed to provide an understanding of how pharmaceutical companies discover, develop, and bring drugs and biopharmaceuticals to market. This course will focus on the development of traditional and biological drugs. The course will follow the process of drug development, taking the drug substance through the process of becoming a drug product, and then into clinical development and commercialization. Case studies from industry will be presented detailing companies and products that utilize state-of-the-art discovery technologies and advanced drug delivery systems.

MEB306-F Bioprocess Fundamental Laboratory (Vector & Strain Design & Development)

The purpose of this basic laboratory course is to provide the students with hand on experience in design and construction of the most widely applicable vector designs. There are a large number of variations possible in the design of vectors depending on, for example, the expression system and the uses they are put to. This course focuses on teaching the students the basic approaches and methods used in the laboratory and in a manufacturing. Students will gain knowledge of the use of selectable markers, promoters, vector targeting and linearization and analytical methods such as southern blot analyses.

MEB307-F-Biochemistry

This introductory course in basic principles of biochemistry is intended for science-track students, e.g. chemical and mechanical engineers with no prior knowledge of life sciences. The Course will cover basic properties, functions and properties of simple peptides, proteins and monoclonal antibodies, carbohydrates, and lipids; introduction to cell factory – cellular reactions involved in cell growth and metabolism, translation, transcription, and replication. Basic principle of protein expression and purification.

MEB309-F Introduction to Bioscience industry (including writing)

The course will equip students with an understanding of conceptual frameworks in market strategy and market assessment with reference to bioscience industries. These topics will be explored with reference to the commercialization of academic science into commercial ventures. We will examine industry dynamics within different segments of the life science industries, such as therapeutics, diagnostics, and medical devices. This includes evaluating common business models employed by entrepreneurial firms, and an introduction to analytical tools used to assess the attractiveness of a variety of life science marketplaces. Common tools used for market research, such as survey methods and qualitative interview based techniques, will be introduced. The course contains a client-sponsored team-project, in which students will conduct market research on a life science technology being commercialized by a university or start-up biotechnology company.

MEB308-S Finance and Accounting Principles

This is a half course survey of Financial Accounting. Accounting is frequently referred to as the “language of business,” and thus, is an essential tool for all managers who strive to be effective communicators. The course involves the study of accounting from the perspective of the data user (an investor, manager, or lender), not the data provider (controller, CPA, etc.). Because of the breadth of this course, it is not reasonable to expect a student to master the subject matter. Instead, the goal of the course is to gain an appreciation and understanding of the topics covered. This does not mean that the technical aspects of accounting will be ignored, but rather that they will not be the central focus of learning. The educational goal of ALS 350 is for each student to become a competent user of accounting information. Students will learn how to interpret, understand, and use the basic financial statements. As part of this learning process, we will investigate the various rules utilized in the preparation of financial statements, the flexibility that exists in the application of these rules, the possible incentives that corporate managers face when selecting the various rules to apply, and the alternative outputs that result from these accounting policy choices.

MEB310-S Mammalian Cell culture technology

Mammalian cell biotechnology has undergone explosive growth over the last 30 years. Persons skilled in mammalian cell biotechnology are in high demand. The primary goal of this course is to provide students with an advanced background in mammalian cell biotechnology. The scientific, engineering, and practical industrial aspects will be presented through a series of lectures and student group presentations. Students learn and understand safety regulations and protocols, particularly as they apply to mammalian cell culture lab, as well as aseptic technique and methods to maintain pure cell cultures, free of contamination. The will acquire skills to collect, analyze, and present information regarding industry-standard practices for maintaining freedom from contamination and proper containment upon scale up, for both mammalian cell culture processes as well as bioprocesses involving other expression systems and/or host cells . They will gain knowledge of the history and status of mammalian cell biotechnology, including past, current and future products, as well as challenges faced and forthcoming, including process economics, speed to the clinic, product quality issues, safety, contamination and containment, scale up and manufacturing capacity. Students will study and understand the biology of cultured cells, including cell growth, death, physiology, mortality, transformation, differentiation, and adaptation. The ability to quantitatively analyze and model cell culture kinetics, including growth, death, and metabolism. They will gain knowledge of cell line engineering techniques and common host cell lines for recombinant protein and vaccine production. They will develop the ability to formulate cell culture medium and develop feeding strategies so as to control certain aspects of cell metabolism and enhance product safety and efficacy. They will gain a general (not engineering-level) understanding of the design of various cell culture bioreactor reactors and culture vessels.

MEB 311-S Bioseparation Engineering Science

The primary goal of this course is to provide students with an advanced background in bio-separations science and engineering including unit operations of chromatography, centrifugation, depth filtration, tangential flow filtration, precipitation and crystallization.

MEB312-S Fundamentals of Microbial Fermentation

Microbial fermentation generates products for every facet of life. The technology is used in the food, pharmaceutical, biologics, enzyme, and green technology industries, as a few examples. This course will provide students with hands-on experience setting up, operating and analyzing fermentations. Students will learn how to conduct growth studies in shake flasks and in a fermenter, induce protein production and perform assays to measure growth and product yields. Experiments will be conducted with a microbial strain expressing a protein. Good documentation is key for regulated industries and will be a key feature for assessing student performance in the course. Students will keep accurate detailed experimental plans, lab notebooks, batch records, analysis results and experimental reports. Teams will give oral presentations of their results and participate in group discussions comparing the different results.

MEB313-S Bioprocess Laboratory Course 1 (Upstream Cell Culture)

This laboratory course provides extensive hands-on experience in KGI’s lab-scale pilot plant for animal cell culture (part of the Amgen Bioprocessing Center). The pilot plant includes several 2-L glass bioreactors plus various single use systems, all run as scale-down models of large scale (25,000-L) systems. The course includes not only laboratory exercises and written reports, but also certain weekly classes wherein students will receive additional instruction, occasionally give presentations on their results, and see talks and demonstrations by vendors on their latest technologies.

MEB314-S Bioprocess Laboratory Course 2 (Upstream Microbial)

Microbial fermentation generates products for every facet of life. The technology is used in the food, pharmaceutical, biologics, enzyme, and green technology industries, as a few examples. This course will provide students with hands-on experience setting up, operating and analyzing fermentations. Students will learn how to conduct growth studies in shake flasks and in a fermenter, induce protein production and perform assays to measure growth and product yields. Experiments will be conducted with a microbial strain expressing a protein. Good documentation is key for regulated industries and will be a key feature for assessing student performance in the course. Students will keep accurate detailed experimental plans, lab notebooks, batch records, analysis results and experimental reports. Teams will give oral presentations of their results and participate in group discussions comparing the different results.

MEB315-S Bioprocess Laboratory Course 3 (Bioseparation)

This laboratory course provides hands-on experience with many of the techniques and principles taught in the complimentary lecture course, listed in this proposal. A student cannot take ALS 422 without taking this lecture course at the same time, or at a prior time. The experiments are designed to teach the students a broad understanding of these key issues in downstream bio-separation operations including chromatography and tangential flow and depth filtration. Following the course the students will gain a thorough understanding of unit operations downstream of bioreactor.

MEB316-S Biotechnology-Based Therapeutics

Advances in genomics, proteomics, recombinant protein technology and structural biology have created opportunities and challenges for the biotech and pharmaceutical industries. This course will provide students with a background of the scientific basis of some key aspects of biotechnology based drug, biologic and vaccine design, discovery and development process. Students will learn about therapeutic and vaccine targets, and how the drugs and vaccines are designed, tested and produced. They will also learn about recently developed biological pharmaceuticals along with many of the current targets of pharmaceutical companies. The mechanism of many of the current biotechnology-based therapeutics will be discussed. In addition, the elements involved in the development a biotechnology company will be taught. Environmental, ethical, regulatory, patent, economic and social issues related to biotechnology-based therapeutics will also be discussed

MEB317-F/S CMC Quality & Regulatory – Principles and Applications (3 credit)

This course will provide an introduction to the concepts and requirements for global pharmaceutical quality and regulatory compliance. The development of international harmonization for drug development and manufacture has made expert knowledge of these areas essential for pharmaceutical engineers and other professionals. The ICH guidelines have mandated a quality by design approach for drug development on continuous improvement as a goal of the quality system within orgaizations. Quality by Design, Process Analytical Technology (PAT) and Critical Quality Attributes (product and process) were introduced by the regulatory agencies (FDA) to provide the foundation for ensuring that product quality, safety and efficacy are built into process during design and not introduced as an afterthought. This introductory course provides the basic principles of QBD, PAT and CQAs using case studies and definition and terms relevant to understanding how a modern biopharmaceutical products are developed and marketed in a highly regulated environment.

The course will also provide students with working knowledge of global regulatory requirements for Chemistry, Manufacturing, and Controls (CMC). The students will become versed in the ICH Quality guidelines that dictate how new products should be developed and post approval changes designed and executed in the most efficient manner. Students will be introduced to definitions and terminology used by regulatory agencies through case histories; ICH, Fast-track approval, post approval changes. The course will review approaches for traditional products such as growth factors and monoclonal antibodies well as cell therapies and the emerging area of biosimilars. This is a pre-requisite course for all other courses in CMC Quality and Regulatory courses that follow.

This course is a pre-requisite to subsequent courses in Regulatory & Quality.

MEB318-O Study Abroad

This is a research-based option. This course is identical to the MEB 321-O Research Project except that the research project is carried out in an academic laboratory that is close collaboration with the Amgen Bioprocessing Center at KGI.

MEB 319-O Industry Internship

This is an optional course for students who wish to spend a summer semester in relevant industry. Following approval of the company for internship, students are expected to work on topics and problems that enhances their understanding and knowledge of the biopharmaceutical industry. Assessment will be performed via a final report and formal presentation to faculty at the end of the internship.

MEB 320-O Team Masters Project

The Team Master’s Project (TMP) is the activity for second-year Master of Business and Science (MBS) students and for Postdoctoral Professional Masters (PPM) students. It is assigned 2-course units each semester for a total of 4 course units and a passing grade in both semesters is required for graduation with an MBS or PPM degree.

The students work in teams of three to six students on professional life science projects which typically focus on business, regulatory, technical or marketing challenges of a commercial life science company

MEB 321-O Research Project

This course is open to students that are interested in getting hands-on bioprocessing research experience. Students will review and present their analysis of real life bioprocess design and development challenge – They will review relevant journal publications to learn how to understand and draw from these. Students will select a suitable bioprocessing research project and prepare an accompanying research proposal. They will present and defend their proposal to the instructor panel and the other students. The students will conduct the research independently or as part of a team, followed by presenting and defending their findings to the instructor panel and the other students. Each student/team will provide a written report for a final grade.

Although all research projects will have a bioprocessing focus, there is a wide range of latitude allowed. The projects may cover anything from CHO or stem cell culture to bio separations. It is expected that most projects will be lab based and will take advantage of the extensive equipment and facilities of the Amgen Bioprocessing Center at KGI. However, the projects need not be lab based, and may even be primarily focused on the business aspects of bioprocessing. For instance, construction of a new SuperPro process model complete with economic analysis would make for a suitable project. Development of a new theoretical approach or mechanistic model would also make for a suitable project. The course instructors will gladly offer suggestions for suitable projects. All selected projects will be subject to the approval of the course instructors.

When appropriate, more than one student may work on a given project. Also, when appropriate, certain projects may be continued on to the next semester. Both of these provisions will allow students to take on more complex projects, if so desired. It is expected that certain projects may be suitable for eventual publication in a bioprocessing journal and/or provide preliminary data for future funding applications.

MEB400-F Principles of Bioprocess Engineering Design and Practice

The role of the bioprocess design in the development of a complete plant design. The reiterative nature of design. Equipment design. Types of bioreactor, purification columns, filters, heat exchangers, nano-filters, virus inactivation reactors and their applications in biotechnology. Design and scale up of each equipment. Process equipment costs and sources of data, cost indices: plant capital cost evaluation, typical distribution of plant capital costs and operating costs. Instrumentation: symbols, subdivision of the process streams and use of control systems: typical applications of flow, pressure, level and temperature control. The concept of loss prevention, Sis Sigma analysis and quality by design (QbD) in a biopharmaceutical industry setting: Doing a job safely, attitudes of mind. Management of safety: Factory Acts; Health and Safety at Work Act: production, storage and transport. Project review procedure: risk assessment, research and development, design, construction and operation. Identification of hazards. Inherently safe design. Hazan and hazard analysis.

Scope of computer-aided process engineering and computer-aided design in process engineering applications. Process flow-sheeting, topology analysis, sequential and simultaneous solution methods. Process flow-sheet simulation.

MEB401-F Biopharmaceutical Quality Assurance and Control (1.5 Credit)

Development and design of production processes for biotechnology products requires comprehensive quality systems that meet global cGMP expectations and are modern quality principles. The spectrum of biologic processes and products has increased in complexity as traditional protein therapeutics become generic (biosimilars) and new cell based therapies are approved. The focus on quality by design in the ICH process and establishment of FDA’s center for pharmaceutical quality reflect the importance of quality and compliance for pharmaceutical engineers.  The many product recalls and regulatory enforcement actions occurring today are frequently the result of poor product and process design resulting in supply shortages and significant loss of corporate reputation.

The goal of this course is to provide students with an advanced understanding of the principles and requirements of biopharmaceutical quality. The course will teach the critical thinking and judgment skills that are needed for the development of quality systems and the resolution of product quality issues. The course will include project assignments designed to assist and integrate into the students second year engineering design project. Quality by Design, Process Analytical Technology (PAT) and Critical Quality Attributes (product and process) will be emphasized to assist students in their design project.

MEB402-F Process Dynamics, Instrumentation and Control

As the biopharmaceutical industry matures bioprocesses are shifting from batch to semi-batch and continues operations. A good example of this trend is the development of bioreactors with continuous perfusion bioreactors becoming the bioreactor of choice for the next generation of platforms. Compared to batch operations, continuous operations rely significantly more on process monitoring, control and automation. This course is intended to introduce students to basic principle of process monitoring and control as applied in a biomanufacturing setting. The course will introduce the concept of quality by design, statistical methods and Process Analytical Technology (PAT) principles. Areas covered include: Controlling the process within pre-set operating condition, optimizing plant operation to produce a good quality product, defining critical process parameters and maintain them within acceptable limits, providing operator interface for monitoring and control via operator console (Human Machine Interface), provide alarm/event logging and trending facilities and generate production data reports.

MEB403-F Chemistry, Manufacturing and Control Regulation of Biologics (1.5 Credit)

Regulatory Chemistry, Manufacturing and Control (CMC) requirements greatly influence strategy for pharmaceutical process development and post approval changes. Knowledge of global CMC requirements is a critical skill in rapid and efficient pharmaceutical approval and compliance. Globalization has created a complex regulatory environment for the manufacture and distribution of pharmaceuticals (and medical devices). Most product supply chains are now multinational with increasing trends towards investment in rapidly developing but poorly regulated nations. The development of regulatory strategies for product development and post approval changes requires the understanding of many national regulatory agencies and international harmonization efforts. The advent of Biosimilars will place increased emphasis on CMC product characterization and process comparability and/or interchangeability as the key criteria for introduction of “generic” biologics.

The primary goal of this course is to provide students with an advanced background in the principles and requirements of regulatory CMC that can be applied to their process design project as well as prepare them for career paths in the regulatory field. Through a series of lectures and case studies this course will teach the critical thinking and judgment skills that are needed for the development of CMC regulatory strategies and influence.

MEB404-F Emerging therapeutics – Stem cells, gene therapy, tissue engineering

Next generation biologics include stem cells, gene therapy a, tissue engineering and regenerative medicine. In this course the students will be given basic understanding of the challenges and opportunities in developing a biopharmaceutical grade product based on these emerging discoveries. Students learn stem cell biology and the challenges regarding clinical testing and commercialization of cell therapies and gene therapies. The ability to collect, analyze, and present information regarding new cell therapy and gene therapy products and processes in development. Different bioreactor design and scale up as well as scalable purification methods will be developed. Through case studies.

MEB405-F Bioprocess Business Plan and Entrepreneurialship

The course is designed to train the students in entrepreneurial leadership in biological – based industries. It consists of two elements. The first element focuses on the practical application of preparing a business plan for new ventures. It centers on bioprocessing of new products and their potential translation into real outcome via a viable business. The second element is designed to introduce the students to the key aspects of implementing the objectives of a business plan once appropriate funding has been obtained.

MEB406-F Planning and Management of Research and Development (R&D)

The course consists of using phase appropriate platform design approach used in the biopharmaceutical industry to take a drug candidate from laboratory to pilot scale and tech transfer to manufacturing. The students will receive instruction on the appraisal of laboratory and pilot scale operations involved in bioprocess sequences and then seek to complete an original investigation into process scale performance for their target product. This will require developing a detailed experimental planning program including predictions of mass and energy balances and of transport phenomena (e.g. heat transfer for removal of metabolic heat, mass transfer for oxygen supply). A dedicated series of individual experiments will be developed. The course will include group discussions with multiple faculty members and visits to Amgen Bioprocessing Center to understand the sequence of operations.

MEB406-F Planning and Management of Research and Development (R&D) in the Biopharmaceutical industry

The biopharmaceutical industry is exceptionally research intensive. The sector spends almost 10 time more per employee on research than any other sector. Effective commercialization of biopharmaceutical drug starts with efficient process design and development that can take up to five years. The aim of this course is to develop the skills of the students to become effective in a research and development environment. Case studies will be sued to teach students how to develop a phase appropriate bioprocess research and development proposal with timelines, budget and deliverables that meets with companies business critical decisions. The research and development plan developed will be integrated into a single roadmap covering preclinical to early and plate phase clinical and tech transfer to manufacturing.

MEB407-F Bioindustry Ethics and Society

The development and use of genomic based technologies is highly regulated and complex process that includes not only drug discovery, bioprocess development and manufacturing but also areas such as law, business, and ethics. The completion of human genome and potential of commercialization of radically new medicines including biologics including stem cells, gene therapy and regenerative medicine have raised many ethical questions. Topics covered in this course include considerations of these issues and their impact on human health care in the 21st Century. These include, for example, the use of animals in tests, design of ethical clinical trials and conflicts of interest.

MEB408-S Team Design Project

This is the capstone project. The students will work in teams to design a complete biomanufacturing plant capable of producing commercial quantities of an API or DP. Each team will work on a separate and specific project leading to a process. Typical example include manufacturing of insulin, human growth hormone, tissue plasminogen activator, monoclonal antibodies for caners, and autoimmune diseases. Students will evaluate potential commercial opportunities and manufacturing options, selecting the expression system, designing the bioreactor, harvesting and purification sequence of operations. A detailed literature survey will be included to understand the best industry practices. Team discussion and consultation with subject matter experts within KGI and with external companies will then be followed leading to specification of the purity profile for the product. This is then followed by preparation of detailed engineering flow sheet that includes each unit operation. Selection and sizing of each equipment for each unit operation will then be carried to meet a specified annual demand for the product. Finally an economic evaluation of the process will be carried out to evaluate the cost of good and potential pricing of the product. The final design will be evaluated and interpreted using available simulation and modelling techniques. A group report and individual report will be presented by each student in the team.

“Engineering track”: Students coming to the program with a life science degree will normally take these courses

MEB 300-F Bioprocess Engineering Principles

The primary goal of this course is to teach the principles of bioprocess engineering in a way that is accessible to biological scientists, bioengineers, and others who have little or no background in chemical engineering.

The course will: Define bioprocessing – Challenges and opportunities for bioprocessing in the 21st century; Describe and develop basic process flow diagram and flow sheet; Differentiate between upstream and downstream processing; Identify key unit operations in upstream and downstream processes; Identify major items of bioprocessing equipment and their basic function(s) in in a biomanufacturing setting;  Establish differences in protein production using bacteria, yeast, animal, and plant cells;  Describe key principles involved in bioreactor design and operation; Compare and contrast batch, fed-batch and continuous modes of bioreactor operation; Discuss scale-up of bioreactors and criteria to consider in bioreactor scale-up; Describe factors that impact cell growth and metabolism; Discuss the importance of monitoring culture pH, oxygen, temperature and major metabolites in bioreactors; Discuss primary recovery and some of the ways in which protein products are harvested; Describe downstream processes and some of the key unit operations for purification; Describe the importance of viral clearance and inactivation in purified protein products; Describe Buffer exchange and concentration operation using tangential flow filtration; Describe the formulation of purified protein products; Describe the term biosimilars and discuss the development and regulation of biosimilars.

MEB302-F Principle of Bioreaction Engineering

Introduction to (bio) reaction engineering. Definition of terms, classification of (bio)reactions ,kinetics of reaction, rate and order of reaction, methods of determination of the order and rate of reaction. Arrhenius equation. (Bio) Reactor design and performance. Types or reactors. Batch reactors, semi-batch and continuous (perfusion) bioreactors. Mixed flow and plug flow. Calculation and comparison of performance and reactor size. Residence time distributions; E, F and C curves and their application. Methods of measurements of RTD. Models of non-ideal flow, dispersion model and dispersion coefficient, closed and open vessels. Tank in series model and laminar flow models. Bioreactor integration into the process. Process considerations – reaction medium (media composition) – product recovery (yield and titre). Process design methodology. Biopharmaceutical industry examples and case studies. Bioreactor control and operation.

MEB303-F Molecular basis of Disease

The list of diseases with known molecular basis includes infectious diseases, cancers, metabolic diseases and mental health diseases. The idea that some diseases are due to genetic causes, a demonstration of which dates back to the early 20th Century, has now been expanded to include the possibility that all recognized human disorders may involve one or more genetic components of the patient. This course examines the role of genes, proteins and RNA in causing or combating diseases, and emphasizes the current conceptual and analytical tools that are brought to bear, and their limitations, on our understanding.

MEB 322-F Heat transfer Bioprocess operations

Introduction to modes of heat transfer and applications in biochemical engineering operations including sterilization and heat inactivation. Heat transfer by conduction, convection and radiation, heat transfer during boiling and condensation. Unsteady state heat conduction in solids, response time of thermocouples. Fourier’s equation: analytical and numerical solutions, chart solutions. Worked examples. Unsteady state heat convection – cooling and heating of bioreactors – worked examples and case Studies Heat transfer with a phase change, condensation and boiling. Modes of condensation – film-wise condensation, Nusselt’s equation, laminar and turbulent flow condensation over flat plates, vertical and horizontal tubes, condensation over a bank of tubes and inside tubes. Radiation heat transfer – simple treatment, black body radiation. Simple heat exchanger design.

MEB 323-F Fluid Flow and Mass Transfer Bioprocess operations

Mass and Momentum transport: Laminar and turbulent boundary layer flow in pipes and simple geometries. Viscometers. Flow of non-Newtonian fluids. Velocity profile and pressure drops in pipes. Definition of generalized Reynolds number and friction factor for Newtonian and non-Newtonian flow. Application to mass transfers. Mixing and non-Newtonian flow in mechanically agitated vessels, bubble columns and air-lifts bioreactors. Power number and Reynolds number definitions and Power curves for mixing bioreactors. Scale-up and scale-down considerations. Flow past spherical and non-spherical particles. Steady and unsteady-state free and hindered settling. Flow through packed beds, capillary model. Definitions of porosity, permeability and tortuosity. Definition of flow, Carman-Kozeny, Burke-Plummer and Ergun equations. Dimensionless form of Ergun equation. Flow through filter cakes, compressible filter cakes and filter cloth resistance, constant rate and constant pressure filtration equations. Equations of flow through centrifuges, settling time and sigma factor calculations. Equations of centrifugal flow for two immiscible liquid Flow through Flow through fluidized beds, minimum fluidization velocity. Worked out examples. Convective mass transfer processes, the penetration and surface renewal theories, mass transfer coefficients, correlations. Simple mass, heat and momentum analogies.

MEB304-F Molecular Biology and Biotechnology

Students will be exposed to the conceptual foundations of biotechnology and the role played by discoveries and applications of molecular biology principles in advancing biotechnology horizons. This is a case-based course in which students will read landmark original papers and patents that shaped biotechnology, and discuss these in the class. The case-based approach will follow the first few weeks of background material where a more standard lecture style will be used so as to bring students with different backgrounds en par with modern molecular biology.

MEB305-F Drug Development

This course is designed to provide an understanding of how pharmaceutical companies discover, develop, and bring drugs and biopharmaceuticals to market. This course will focus on the development of traditional and biological drugs. The course will follow the process of drug development, taking the drug substance through the process of becoming a drug product, and then into clinical development and commercialization. Case studies from industry will be presented detailing companies and products that utilize state-of-the-art discovery technologies and advanced drug delivery systems.

MEB306-F Bioprocess Fundamental Laboratory (Vector & Strain Design & Development)

The purpose of this basic laboratory course is to provide the students with hand on experience in design and construction of the most widely applicable vector designs. There are a large number of variations possible in the design of vectors depending on, for example, the expression system and the uses they are put to. This course focuses on teaching the students the basic approaches and methods used in the laboratory and in a manufacturing. Students will gain knowledge of the use of selectable markers, promoters, vector targeting and linearization and analytical methods such as southern blot analyses.

MEB309-F Introduction to Bioscience industry (including writing)

The course will equip students with an understanding of conceptual frameworks in market strategy and market assessment with reference to bioscience industries. These topics will be explored with reference to the commercialization of academic science into commercial ventures. We will examine industry dynamics within different segments of the life science industries, such as therapeutics, diagnostics, and medical devices. This includes evaluating common business models employed by entrepreneurial firms, and an introduction to analytical tools used to assess the attractiveness of a variety of life science marketplaces. Common tools used for market research, such as survey methods and qualitative interview based techniques, will be introduced. The course contains a client-sponsored team-project, in which students will conduct market research on a life science technology being commercialized by a university or start-up biotechnology company.

MEB310-S Mammalian Cell culture technology

Mammalian cell biotechnology has undergone explosive growth over the last 30 years. Persons skilled in mammalian cell biotechnology are in high demand. The primary goal of this course is to provide students with an advanced background in mammalian cell biotechnology. The scientific, engineering, and practical industrial aspects will be presented through a series of lectures and student group presentations. Students learn and understand safety regulations and protocols, particularly as they apply to mammalian cell culture lab, as well as aseptic technique and methods to maintain pure cell cultures, free of contamination. The will acquire skills to collect, analyze, and present information regarding industry-standard practices for maintaining freedom from contamination and proper containment upon scale up, for both mammalian cell culture processes as well as bioprocesses involving other expression systems and/or host cells . They will gain knowledge of the history and status of mammalian cell biotechnology, including past, current and future products, as well as challenges faced and forthcoming, including process economics, speed to the clinic, product quality issues, safety, contamination and containment, scale up and manufacturing capacity. Students will study and understand the biology of cultured cells, including cell growth, death, physiology, mortality, transformation, differentiation, and adaptation. The ability to quantitatively analyze and model cell culture kinetics, including growth, death, and metabolism. They will gain knowledge of cell line engineering techniques and common host cell lines for recombinant protein and vaccine production. They will develop the ability to formulate cell culture medium and develop feeding strategies so as to control certain aspects of cell metabolism and enhance product safety and efficacy. They will gain a general (not engineering-level) understanding of the design of various cell culture bioreactor reactors and culture vessels.

MEB308-S Finance and Accounting Principles

This is a half course survey of Financial Accounting. Accounting is frequently referred to as the “language of business,” and thus, is an essential tool for all managers who strive to be effective communicators. The course involves the study of accounting from the perspective of the data user (an investor, manager, or lender), not the data provider (controller, CPA, etc.). Because of the breadth of this course, it is not reasonable to expect a student to master the subject matter. Instead, the goal of the course is to gain an appreciation and understanding of the

MEB 311-S Bioseparation Engineering Science

The primary goal of this course is to provide students with an advanced background in bio-separations science and engineering including unit operations of chromatography, centrifugation, depth filtration, tangential flow filtration, precipitation and crystallization.

MEB312-S Fundamentals of Microbial Fermentation

Microbial fermentation generates products for every facet of life. The technology is used in the food, pharmaceutical, biologics, enzyme, and green technology industries, as a few examples. This course will provide students with hands-on experience setting up, operating and analyzing fermentations. Students will learn how to conduct growth studies in shake flasks and in a fermenter, induce protein production and perform assays to measure growth and product yields. Experiments will be conducted with a microbial strain expressing a protein. Good documentation is key for regulated industries and will be a key feature for assessing student performance in the course. Students will keep accurate detailed experimental plans, lab notebooks, batch records, analysis results and experimental reports. Teams will give oral presentations of their results and participate in group discussions comparing the different results.

MEB313-S Bioprocess Laboratory Course 1 (Upstream Cell Culture)

This laboratory course provides extensive hands-on experience in KGI’s lab-scale pilot plant for animal cell culture (part of the Amgen Bioprocessing Center). The pilot plant includes several 2-L glass bioreactors plus various single use systems, all run as scale-down models of large scale (25,000-L) systems. The course includes not only laboratory exercises and written reports, but also certain weekly classes wherein students will receive additional instruction, occasionally give presentations on their results, and see talks and demonstrations by vendors on their latest technologies.

MEB314-S Bioprocess Laboratory Course 2 (Upstream Microbial)

Microbial fermentation generates products for every facet of life. The technology is used in the food, pharmaceutical, biologics, enzyme, and green technology industries, as a few examples. This course will provide students with hands-on experience setting up, operating and analyzing fermentations. Students will learn how to conduct growth studies in shake flasks and in a fermenter, induce protein production and perform assays to measure growth and product yields. Experiments will be conducted with a microbial strain expressing a protein. Good documentation is key for regulated industries and will be a key feature for assessing student performance in the course. Students will keep accurate detailed experimental plans, lab notebooks, batch records, analysis results and experimental reports. Teams will give oral presentations of their results and participate in group discussions comparing the different results.

MEB315-S Bioprocess Laboratory Course 3 (Bioseparation)

This laboratory course provides hands-on experience with many of the techniques and principles taught in the complimentary lecture course, listed in this proposal. A student cannot take ALS 422 without taking this lecture course at the same time, or at a prior time. The experiments are designed to teach the students a broad understanding of these key issues in downstream bio-separation operations including chromatography and tangential flow and depth filtration. Following the course the students will gain a thorough understanding of unit operations downstream of bioreactor.

MEB316-S Biotechnology-Based Therapeutics

Advances in genomics, proteomics, recombinant protein technology and structural biology have created opportunities and challenges for the biotech and pharmaceutical industries. This course will provide students with a background of the scientific basis of some key aspects of biotechnology based drug, biologic and vaccine design, discovery and development process. Students will learn about therapeutic and vaccine targets, and how the drugs and vaccines are designed, tested and produced. They will also learn about recently developed biological pharmaceuticals along with many of the current targets of pharmaceutical companies. The mechanism of many of the current biotechnology-based therapeutics will be discussed. In addition, the elements involved in the development a biotechnology company will be taught. Environmental, ethical, regulatory, patent, economic and social issues related to biotechnology-based therapeutics will also be discussed.

MEB317-F/S CMC Quality & Regulatory – Principles and Applications (3 Credit)

With the growth of the biologics over the past two decades, companies are moving towards a science based, rather than empirical based approach, to product and process design and commercialization. Quality by Design, Process Analytical Technology (PAT) and Critical Quality Attributes (product and process) were introduced by the regulatory agencies (FDA) to provide the foundation for ensuring that product quality, safety and efficacy are built into process during design and not introduced as an afterthought. This introductory course provides the basic principles of QBD, PAT and CQAs using case studies and definition and terms relevant to understanding how a modern biopharmaceutical products are developed and marketed in a highly regulated environment.

The course will develop students skills in regulatory principles and how to apply them to commercialize biologics including legacy products such as peptides, proteins and monoclonal antibiosis well as the next generation biologics, e.g. stem cells, gene therapy products, tissue engineered products and regenerative medicine products. Students will be introduced to definitions and terminology used by regulatory agencies through case histories; ICH, Fast-track approval, post approval, biosimilars. This is a pre-requisite course for all other courses in CMC Quality and Regulatory courses that follow.

This course is a pre-requisite to subsequent courses in Regulatory & Quality

MEB318-O Study Abroad

This is a research-based option. This course is identical to the MEB 321-O Research Project except that the research project is carried out in an academic laboratory that is close collaboration with the Amgen Bioprocessing Center at KGI.

MEB 319-O Industry Internship

This is an optional course for students who wish to spend a summer semester in relevant industry. Following approval of the company for internship, students are expected to work on topics and problems that enhances their understanding and knowledge of the biopharmaceutical industry. Assessment will be performed via a final report and formal presentation to faculty at the end of the internship.

MEB 320-O Team Masters Project

The Team Master’s Project (TMP) is the activity for second-year Master of Business and Science (MBS) students and for Postdoctoral Professional Masters (PPM) students. It is assigned 2-course units each semester for a total of 4 course units and a passing grade in both semesters is required for graduation with an MBS or PPM degree.

The students work in teams of three to six students on professional life science projects which typically focus on business, regulatory, technical or marketing challenges of a commercial life science company.

MEB 321-O Research Project

This course is open to MBS, MS, PPC and PPM students that are interested in getting hands-on bioprocessing research experience. Students will review and present their analysis of one or two bioprocessing journal publications to learn how to understand and draw from these. Students will select a suitable bioprocessing research project and prepare an accompanying research proposal. They will present and defend their proposal to the instructor panel and the other students. The students will conduct the research independently or as part of a team, followed by presenting and defending their findings to the instructor panel and the other students. Each student/team will provide a written report for a final grade.

Although all research projects will have a bioprocessing focus, there is a wide range of latitude allowed. The projects may cover anything from CHO or stem cell culture to bio separations to fermented beverages to biofuels. It is expected that most projects will be lab based and will take advantage of the extensive equipment and facilities of the Amgen Bioprocessing Center at KGI. However, the projects need not be lab based, and may even be primarily focused on the business aspects of bioprocessing. For instance, construction of a new SuperPro process model complete with economic analysis would make for a suitable project. Development of a new theoretical approach or mechanistic model would also make for a suitable project. The course instructors will gladly offer suggestions for suitable projects. All selected projects will be subject to the approval of the course instructors.

When appropriate, more than one student may work on a given project. Also, when appropriate, certain projects may be continued on to the next semester. Both of these provisions will allow students to take on more complex projects, if so desired. It is expected that certain projects may be suitable for eventual publication in a bioprocessing journal and/or provide preliminary data for future funding applications.

MEB400-F Principles of Bioprocess Engineering Design and Practice

The role of the bioprocess design in the development of a complete plant design. The reiterative nature of design. Equipment design. Types of bioreactor, purification columns, filters, heat exchangers, nano-filters, virus inactivation reactors and their applications in biotechnology. Design and scale up of each equipment. Process equipment costs and sources of data, cost indices: plant capital cost evaluation, typical distribution of plant capital costs and operating costs. Instrumentation: symbols, subdivision of the process streams and use of control systems: typical applications of flow, pressure, level and temperature control. The concept of loss prevention, Sis Sigma analysis and quality by design (QbD) in a biopharmaceutical industry setting: Doing a job safely, attitudes of mind. Management of safety: Factory Acts; Health and Safety at Work Act: production, storage and transport. Project review procedure: risk assessment, research and development, design, construction and operation. Identification of hazards. Inherently safe design. Hazan and hazard analysis.

Scope of computer-aided process engineering and computer-aided design in process engineering applications. Process flow-sheeting, topology analysis, sequential and simultaneous solution methods. Process flow-sheet simulation

MEB401-F Biopharmaceutical Quality Assurance and Control (1.5 Credit)

Biotechnology has created more than 200 new therapies and production levels now routinely exceed metric tons for many antibodies. Product complexity has also increased as stem cell therapies have entered clinical studies and the first antilogous cellular therapies have recently been approved in the United States. In turn, ensuring product quality has grown in importance and complexity. Instances of product recalls and regulatory enforcement actions are frequent and result in supply shortages and significant loss of corporate reputation and value. Production of biotechnology products requires comprehensive quality standards and systems that meet global cGMP expectations and are based upon thorough scientific knowledge of the product and process.

Persons knowledgeable in the principles and practice of biopharmaceutical quality management are in high demand and hold positions of significant responsibility within the private and public sectors of the healthcare industry. The primary goal of this course is to provide students with an advanced background in the principles and requirements of biopharmaceutical quality assurance and control. Through a series of lectures and case studies this course will teach the critical thinking and judgment skills that are needed for the development of quality systems and the resolution of product quality issues.

MEB402-F Process Dynamics, Monitoring & Control

As the biopharmaceutical industry matures bioprocesses are shifting from batch to semi-batch and continues operations. A good example of this trend is the development of bioreactors with continuous perfusion bioreactors becoming the bioreactor of choice for the next generation of platforms. Compared to batch operations, continuous operations rely significantly more on process monitoring, control and automation. This course is intended to introduce students to basic principle of process monitoring and control as applied in a biomanufacturing setting. The course will introduce the concept of quality by design, statistical methods and Process Analytical Technology (PAT) principles. Areas covered include: Controlling the process within pre-set operating condition, optimizing plant operation to produce a good quality product, defining critical process parameters and maintain them within acceptable limits, providing operator interface for monitoring and control via operator console (Human Machine Interface), provide alarm/event logging and trending facilities and generate production data reports.

MEB403-F Chemistry, Manufacturing and Control Regulation of Biologics (1.5 Credit)

Regulatory Chemistry, Manufacturing and Control (CMC) requirements determine the strategy parameters for new pharmaceutical process development and changes post approval. Knowledge of CMC requirements and relevant agencies is a key success factor in pharmaceutical approval and compliance. In particular, globalization has caused a significantly more complex regulatory environment for the manufacture and distribution of pharmaceuticals (and medical devices). Most product supply chains are now multinational with increasing trends towards investment in rapidly developing but poorly regulated nations. The development of regulatory strategies for product development and post approval changes requires the understanding of many national regulatory agencies and international harmonization efforts. The advent of Biosimilars will place increased emphasis on CMC product characterization and process comparability and/or interchangeability as the key criteria for introduction of “generic” biologics.

Often the introduction of product production and distribution improvements is limited by the effectiveness of the Chemistry, Manufacturing, and Control (CMC) regulatory strategy employed by the firm. Understanding of post approval reporting requirements for product deviation and needed field actions is an important responsibility of Regulatory CMC organizations. Requirements vary globally and are subject to strict filing timelines. In addition, management of inspectional schedules and resolution of inspectional findings or other enforcement actions is the responsibility of Regulatory CMC. Effective CMC organizations coordinate with global regulatory agencies to develop risk based approaches to inspection frequency and focus. Similar risk-based approaches are developed with global regulatory agencies to detect and prevent counterfeiting and product diversion. These are increasingly difficult problems in the global environment.

Persons knowledgeable in the principles and practice of regulatory CMC requirements of are in high demand and hold positions of significant responsibility within the private and public sectors of the healthcare industry. The primary goal of this course is to provide students with an advanced background in the principles and requirements of regulatory CMC including Post Approval reporting requirements, deviation reporting, Inspection coordination and resolution, and Good Distribution Practices (GDP) practices. Through a series of lectures and case studies this course will teach the critical thinking and judgment skills that are needed for the development of CMC regulatory strategies and influence.

MEB404-F Emerging therapeutics – Stem cells, gene therapy, tissue engineering

Next generation biologics include stem cells, gene therapy a, tissue engineering and regenerative medicine. In this course the students will be given basic understanding of the challenges and opportunities in developing a biopharmaceutical grade product based on these emerging discoveries. Students learn stem cell biology and the challenges regarding clinical testing and commercialization of cell therapies and gene therapies. The ability to collect, analyze, and present information regarding new cell therapy and gene therapy products and processes in development. Different bioreactor design and scale up as well as scalable purification methods will be developed. Through case studies.

MEB405-F Bioprocess Business Plan and Entrepreneurialship

The course is designed to train the students in entrepreneurial leadership in biological – based industries. It consists of two elements. The first element focuses on the practical application of preparing a business plan for new ventures. It centers on bioprocessing of new products and their potential translation into real outcome via a viable business. The second element is designed to introduce the students to the key aspects of implementing the objectives of a business plan once appropriate funding has been obtained.

MEB406-F Planning and Management of Research and Development (R&D) in the Biopharmaceutical industry

The biopharmaceutical industry is exceptionally research intensive. The sector spends almost 10 time more per employee on research than any other sector. Effective commercialization of biopharmaceutical drug starts with efficient process design and development that can take up to five years. The aim of this course is to develop the skills of the students to become effective in a research and development environment. Case studies will be sued to teach students how to develop a phase appropriate bioprocess research and development proposal with timelines, budget and deliverables that meets with companies business critical decisions. The research and development plan developed will be integrated into a single roadmap covering preclinical to early and plate phase clinical and tech transfer to manufacturing.

MEB407-F Bioindustry Ethics and Society

The development and use of genomic based technologies is a highly regulated and complex process that includes not only drug discovery, bioprocess development and manufacturing but also areas such as law, business, and ethics. The completion of human genome and potential of commercialization of radically new medicines including biologics including stem cells, gene therapy and regenerative medicine have raised many ethical questions. Topics covered in this course include considerations of these issues and their impact on human health care in the 21st Century. These include, for example, the use of animals in tests, design of ethical clinical trials and conflicts of interest.

MEB408-S Team Design Project

This is the capstone project. The students will work in teams to design a complete biomanufacturing plant capable of producing commercial quantities of an API or DP. Each team will work on a separate and specific project leading to a process. Typical example include manufacturing of insulin, human growth hormone, tissue plasminogen activator, monoclonal antibodies for caners, and autoimmune diseases. Students will evaluate potential commercial opportunities and manufacturing options, selecting the expression system, designing the bioreactor, harvesting and purification sequence of operations. A detailed literature survey will be included to understand the best industry practices. Team discussion and consultation with subject matter experts within KGI and with external companies will then be followed leading to specification of the purity profile for the product. This is then followed by preparation of detailed engineering flow sheet that includes each unit operation. Selection and sizing of each equipment for each unit operation will then be carried to meet a specified annual demand for the product. Finally an economic evaluation of the process will be carried out to evaluate the cost of good and potential pricing of the product. The final design will be evaluated and interpreted using available simulation and modelling techniques. A group report and individual report will be presented by each student in the team.

**WASC Approved