Purdue University School of Chemical Engineering GRADUATE SEMINAR SERIES Dr. James N. Michaels Senior Scientific Director, Merck & Company "Development of Material Attribute Design Spaces for Particulate Dosage Forms" November 13, 2012 9:00-10:15 a.m. FRNY G140 Reception at 8:30 a.m. in Henson Atrium Abstract: Manufacturing in the pharmaceutical industry is strictly regulated by national and regional regulatory agencies. The regulations, which require that manufacturing operates under "current good manufacturing practices" (cGMPs), significantly constrain the type and extent of changes that can be made to manufacturing processes and process equipment once a product is in commercial production. Historically, this has impeded the implementation of new process technologies and the application of continuous improvement methodologies that are common in other industries. In recognition of this issue, the FDA created the "GMPs in the 21st Century" initiative, an updating of GMP principles that are articulated in a series of guidances issued by the International Council on Harmonization (ICH). Central to the new GMP paradigm is the concept of a "design space", a multidimensional space defined by key process and material variables in which final product quality is assured. In principal, this provides manufacturers flexibility to make some process changes without regulatory impact. As defined in the ICH guidances, a design space depends on the scale and design of process equipment, therefore the regulatory flexibility is limited to relatively modest changes in operating points. In general, changes in equipment or scale require development of a new design space with subsequent regulatory review and approval before the change can be implemented. This talk discusses the practicality and limitations of defining a design space strictly in terms of material attributes rather than process variables. This material-attribute design space is independent of scale and configuration of process equipment and the associated process variables. For this reason, it should be portable in the sense that post-approval changes of equipment scale, nameplate, or location would not require regulatory approval. The key principles and assumptions of this approach are discussed, and a number of short case studies from manufacture of solid oral dosage forms are presented to illustrate how modern understanding of particle technology and particulate systems can be applied to develop and implement such a design space. Bio: Jim Michaels is Scientific Associate Vice President and head of the Center for Materials Science and Engineering in the manufacturing division of Merck & Co., Inc. This group is a materials science and particle technology laboratory that supports pharmaceutical and biosterile product development and manufacturing. In addition, he has served for the last 10 years as Technical Committee Chair of the International Fine Particle Research Institute (IFPRI), a global, cross-sector industrial research consortium. Jim's research interests (when his day job allows it) include powder flow and particle enlargement through wet and dry granulation, enhanced by a more than 10-year collaboration with Jim Litster. He is a chemical engineer with B.S. and M.S. degrees from U.C. Berkeley and Sc.D. from M.I.T.