Theodore W. Randolph - Bayer HealthCare Pharmaceuticals

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Bayer HealthCare Pharmaceuticals is a global leader in the research, development,
manufacturing and commercialization of innovative biotechnology and specialty pharmaceutical
products. Our campuses at Berkeley, Emeryville and Richmond form the core of our
global biotechnology operations.
Bayer HealthCare Pharmaceuticals is the sixth largest biotechnology company in the
world and is the second largest biotechnology employer in the San Francisco Bay Area. More
than 2000 people dedicated to every field of biotechnology, including research, clinical and
process development, manufacturing and commercialization make up the Bayer family in the
Bay Area. We also have an unwavering commitment to investing in our Bay Area communities.
We’ve been recognized for our efforts towards protecting the environment, sponsoring
innovative science education and workforce development programs and promoting a
diverse workforce. In keeping with our mission of Science for a Better Life, and by leveraging
the innovation potential of the Bay Area, we are poised to deliver the next generation of
biotherapeutics that address unmet medical needs and improve human health.
COLLEGE OF CHEMISTRY
B E R K E L E Y
Gregory Stephanopoulos
E. Terry Papoutsakis
Douglas A. Lauffenburger
George Georgiou
Frances Arnold
Bernhard Palsson
Linda G. Griffith
Michael J. Betenbaugh
The Bayer Lectures
in Biochemical Engineering
University of California, Berkeley
Theodore W. Randolph
Gillespie Professor of Bioengineering
Co-Director, Center for Pharmaceutical Biotechnology
Department of Chemical and Biological Engineering
University of Colorado at Boulder
Engineering Challenges of Protein
Formulations
Wednesday, January 30, 2008
4:00 p.m.
Pitzer Auditorium, 120 Latimer Hall
Reception to follow in 775 Tan Hall

Engineering Challenges of Protein
Formulations
Protein therapeutics offer remarkable potential benefits to human health.
Indeed, they form the fastest-growing new class of drugs. But because the
mechanism of their action depends on their three-dimensional molecular
conformation, this proper conformation must be preserved not only through
production, but also through the drug’s shelf life and eventual delivery to
patients. Thus, the engineer must deliver a purification process that yields a
chemically and conformationally pure product, and also a set of conditions
(temperature, pH, solution additives, container materials, etc., collectively
called the formulation) that maintains these purities.
In this talk, two examples of formulation engineering will be discussed.
The first will explore the thermodynamic effects of formulation solutes on
the kinetics of protein aggregation. Protein aggregation kinetics typically are
modeled using the modified Lumry-Eyring framework, which assumes that
the compact native protein exists in an equilibrium with reactive partially
unfolded species that form the transition state for aggregation. These
partially unfolded intermediates react through collisions with themselves
(or existing aggregates) to form aggregates (or larger aggregates). Under
favorable solution conditions described by the Wyman linkage relationship the
equilibrium between the native state and the transition state intermediates
can be shifted to favor the native state, reducing the concentration of reactive
intermediates and, consequently, the rate of aggregation.
The second example explores kinetic control of protein degradation
reactions. Lyophilization can be used to create formulations of proteins
contained in glassy matrices. Within these glassy matrices, some (but not
all) undesirable degradation may be significantly inhibited. Rational design
of lyophilization processes and the resulting glassy state formulations offer
promise of ultra-stable protein therapeutics and vaccines; the particular
example of development of a botulism vaccine will be discussed.
Theodore W. Randolph
Theodore W. “Ted” Randolph received
his Ph.D. in chemical engineering
at the University of California, Berkeley,
in 1987. He worked as a post-doctoral fellow
at the École Polytechnique Fédérale de
Lausanne and then joined the Department
of Chemical Engineering at Yale University
as an assistant professor. After promotion
to associate professor, he was named to
Yale’s first John J. Lee Junior Professorship
in Chemical Engineering.
In 1993, Dr. Randolph accepted the
Patton Associate Professorship in the
Department of Chemical Engineering
at the University of Colorado at Boulder. He currently serves as the Gillespie
Professor of Bioengineering, co-director of the University of Colorado’s Center for
Pharmaceutical Biotechnology, and Director of the NIH Leadership Training in
Pharmaceutical Biotechnology Program.
Dr. Randolph is a National Science Foundation Presidential Young
Investigator, and he has received the AIChE Professional Progress Award
and the American Pharmacist’s Ebert Prize. His research interests include
biopharmaceutical formulation, lyophilization of proteins, protein-solvent
interactions in non-aqueous environments, and protein refolding.
Dr. Randolph is an inventor on numerous patents, some of which form the
basis for two companies that he has founded: RxKinetix (now owned by Endo
Pharmaceuticals), a company formed to commercialize new extended-release
drug delivery technologies; and BaroFold, a company that uses high-pressure
protein refolding technology to develop and produce new protein therapeutics.