A Roadmap to Biomanufacturing

Transcription

1 MASSACHUSETTS INSTITUTE OF TECHNOLOGY A Roadmap to Biomanufacturing

2 INTRODUCTION Join us in Principles of Biomanufacturing: Using Biotechnology to Manufacture Medicines and earn 3 CEUs and a MIT Professional Certificate. Connect and learn from an international community of professionals in the biomanufacturing field. Go on virtual field trips to Pfizer and Biogen to see biomanufacturing equipment in action. Featuring experts from: Leading biopharmaceutical companies, such as Amgen, Biogen, and Pfizer. Regulatory agencies such as the FDA. All materials 2017 Massachusetts Institute of Technology. 1

3 MEET YOUR INSTRUCTORS PROF. CHRIS LOVE J. Christopher Love is an Associate Professor of Chemical Engineering at the Koch Institute for Integrative Cancer Research at MIT. He is also an Associate Member of the Broad Institute, and an Associate Member at the Ragon Institute of MGH, MIT, and Harvard. Love earned a B.S. in chemistry from the University of Virginia and a Ph.D. in physical chemistry at Harvard University under the supervision of George Whitesides. Following completion of his doctoral studies, he extended his research into immunology at Harvard Medical School with Hidde Ploegh from , and at the Immune Disease Institute from Photo Credit: Lillie Paquette DR. PAUL BARONE Paul W. Barone has been at the MIT Center for Biomedical Innovation (CBI) since He is currently the Director of two biopharmaceutical industry consortia housed at MIT s Center for Biomedical Innovation (CBI): the Biomanufacturing Research Program (BioMAN) and the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB). Prior to joining CBI, Dr. Barone earned an M.S and Ph.D. in Chemical and Biomolecular Engineering from the University of Illinois, Urbana-Champaign, where his research focused on the development of novel nanoscale sensors for the detection of a variety of biologically relevant analytes, such as hydrogen peroxide, glucose and troponin. Photo Credit: David Parnes Photo Credit: David Parnes DR. STACY SPRINGS Dr. Stacy Springs is the Senior Director of Programs at MIT s Center for Biomedical Innovation (CBI) and the Executive Director of both MIT s Biomanufacturing Program (BioMAN) and its Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB). These academic-industry consortia are focused on pre-competitive collaboration to enable the delivery of affordable, safe and effective biopharmaceuticals. In addition, Stacy is the Associate Institute Director of the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL). Dr. Springs holds a Ph.D. in Chemistry from the University of Texas at Austin and gained postdoctoral training in protein and biophysical chemistry at Princeton University. All materials 2017 Massachusetts Institute of Technology. 2

4 A ROADMAP TO BIOMANUFACTURING The worst thing that could happen is that we find a breakthrough medicine and then we don t know how to make it, or even worse, we can only make so small quantities that we have to choose who gets help and who does not. I think we create tremendous value by making medicines available in large quantities and at affordable prices. JORG THOMMES The goal of modern biomanufacturing is to economically produce enough biologic drug to meet medical demand. But to do this efficiently you need to understand not just how the pieces fit together, but how they also impact one another. In that sense, biomanufacturing is quite similar to planning a vacation. Just as you need to know where you are starting, where you are going, and the possible routes between the two, you need to understand the unique features of the active biologic molecule, and the target composition of your final drug product. Senior Vice President Pharmaceutical Sciences & Technology Visterra Both the type of cells that you choose to produce your protein therapeutic, and the final product itself, influence your choices in manufacturing. And just as your final destination may dictate the route you take on your trip, the final biologic product may dictate the processing steps required to make a safe and effective biologic drug. Figure 1 Planning a Vacation Biopharmaceutical manufacturing is similar to planning a vacation. For example, if you want to travel from New York to San Francisco, you could drive a car to Chicago and then fly, or drive the entire way. The choices you make early in your planning impact all aspects of your trip. All materials 2017 Massachusetts Institute of Technology. 3

5 A ROADMAP TO BIOMANUFACTURING But what are the typical steps in manufacturing a biologic drug? The process starts with cell line development. Modern biomanufacturing uses the machinery of living cells to produce our target product. Here we will choose the type of cell we will use and will identify unique clonal variants that produce the largest quantity of our target biologic drug, while also maintaining its quality. At the end of this process, we will have identified one single clone that will be used throughout the rest of the manufacturing process. The next step is known as upstream processing. In upstream processing, we grow the production cells in large reactors to produce our product. The reactor operating conditions will depend on the chosen cell line and a series of optimization experiments performed at smaller scale during development. At the end of upstream processing, we will likely have tens of thousands of liters of cell culture fluid containing our target product, as well as the host cells, other proteins they may have produced, and any remaining nutrients and components of the media used to sustain cell growth. The next step is known as downstream processing. The role of downstream processing is to purify the biologic drug by using a series of orthogonal steps to remove unwanted components from the cell culture fluid. At the end of downstream processing, we will have a highly pure biologic drug substance. This drug substance is then mixed with other components in a process called fill and finish, to enhance its stability or improve its efficacy, so that it is ready to administer to patients. Figure 2 The Steps in Biomanufacturing Schematic showing the steps of biomanufacturing. First is cell line development, second is upstream processing, third is downstream processing, and last is fill and finish. Note: cell line development is not performed each time a product is manufactured. All materials 2017 Massachusetts Institute of Technology. 4

6 A ROADMAP TO BIOMANUFACTURING Just like planning our vacation, the details within each of these steps depend on our starting biologic molecule and our final product. And over the rest of this course, you will learn about how each choice made along the way impacts manufacturing. Finally, we must keep in mind that all biologic drugs are manufactured and sold with oversight from regulatory agencies, such as the Food and Drug Administration in the US. The goal of these agencies is to ensure that all biologic products are reliably manufactured using good manufacturing practices, and that the final product is safe and efficacious. This means that our manufacturing process is not designed in a vacuum, but with the final goal of leading to the sale of an approved biologic drug. WANT TO KEEP LEARNING? Explore the fundamental principles of biopharmaceutical manufacturing, including upstream and downstream processing, with MIT s online course: Principles of Biomanufacturing: Using Biotechnology to Manufacture Medicines The course starts February 5, Enroll today! All materials 2017 Massachusetts Institute of Technology. 5