Ted Randolph
Gillespie Professor • Center for Pharmaceutical Biotechnology, Co-Director
Chemical and Biological Engineering

Office: JSCBB C227
Mailbox: 596 UCB


B.S., University of Colorado (1983)
Ph.D. University of California, Berkeley (1987)


  • National Academy of Inventors 2021
  • College of Engineering Dean's Faculty Fellowship 2016
  • College of Engineering Dean’s Faculty Fellowship 2011-12
  • AAPS Dale E. Wurster Research Award in Pharmaceutics, 2010
  • Triennial John M. Prausnitz Award in Applied Chemical Thermodynamics, 2009
  • Bioscience Company of the Year - BaroFold, Inc., co-founded by Ted Randolph
  • American Society of Engineering Educators Dow Lectureship Award, 2007
  • Editorial Board Member J. Pharmaceutical Innovation
  • Ebert Award, Best Original Investigation in 2006, American Pharmacists Association
  • American Institute of Chemical Engineers, Professional Progress Award, 2005
  • Boulder Faculty Assembly Research and Creative Work Award 2003
  • College of Engineering and Applied Sciences Max Peters Award for Outstanding Service 2002
  • Editorial Board Member, Journal of Pharmaceutical Sciences
  • Outstanding Graduate Teaching Award, Department of Chemical Engineering, 2000
  • Editorial Board Member, Current Pharmaceutical Biotechnology
  • College of Engineering and Applied Sciences Outstanding Research and Service Award, 1998
  • Invited Foreign Researcher, Japanese Agency of Industrial Science and Technology, 1995
  • Patten Associate Professor Chair in Chemical Engineering, University of Colorado, Boulder, 1993
  • John J. Lee Junior Professorship Chair in Chemical Engineering, Yale University, 1993
  • Senior Faculty Fellowship, Yale University, 1993
  • NSF Presidential Young Investigator Award (1991)

Selected Publications

  • Hassett KJ, Meinerz NM, Semmelmann F, Cousins MC, Garcea RL, Randolph TW 2015. Development of a highly thermostable, adjuvanted human papillomavirus vaccine. Eur J Pharm Biopharm  94:220-228.
  • Chisholm CF, Nguyen BH, Soucie KR, Torres RM, Carpenter JF, Randolph TW 2015. In Vivo Analysis of the Potency of Silicone Oil Microdroplets as Immunological Adjuvants in Protein Formulations. J Pharm Sci  104(11):3681-3690.
  • Shomali M, Tanriverdi S, Freitag AJ, Engert J, Winter G, Siedler M, Kaymakcalan Z, Carpenter JF, Randolph TW 2015. Dose Levels in Particulate-Containing Formulations Impact Anti-drug Antibody Responses to Murine Monoclonal Antibody in Mice. Journal of Pharmaceutical Sciences 104(5):1610-1621.
  • Gerhardt, A; Nguyen, BH; Lewus, R; Carpenter, JF; Randolph, TW 2015. Effect of the Siliconization Method on Particle Generation in a Monoclonal Antibody Formulation in Pre-filled Syringes. Journal of Pharmaceutical Sciences Volume: 104 Issue: 5 Pages: 1601-1609 DOI: 10.1002/jps.24387 
  • Mehta SB, Lewus R, Bee JS, Randolph TW, Carpenter JF 2015. Gelation of a Monoclonal Antibody at the Silicone Oil-Water Interface and Subsequent Rupture of the Interfacial Gel Results in Aggregation and Particle Formation. Journal of Pharmaceutical Sciences 104(4):1282-1290.
  • Hassett KJ, Cousins MC, Rabia LA, Chadwick CM, O'Hara JM, Nandi P, Brey RN, Mantis NJ, Carpenter JF, Randolph TW 2013. Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization. Eur J Pharm Biopharm. 85(2):279-286.
  • Xu Y, Carpenter JF, Cicerone MT, Randolph TW 2013. Contributions of local mobility and degree of retention of native secondary structure to the stability of recombinant human growth hormone (rhGH) in glassy lyophilized formulations. Soft Matter 9(32):7855-7865.
  • Bee, J.S., et al., Production of particles of therapeutic proteins at the air-water interface during compression/dilation cycles. Soft Matter, 2012. 8(40): p. 10329-10335.
  • Britt, K.A., et al., Excipient effects on humanized monoclonal antibody interactions with silicone oil emulsions. Journal of Pharmaceutical Sciences, 2012. 101(12): p. 4419-4432.

Research Interests

Stabilization and Formulation of Therapeutic Proteins- Converting Molecules into Drugs: 

Protein-based pharmaceuticals are the fastest-growing class of new drugs. They not only offer promise for treatments to address major health challenges such as cancer, but also a wealth of new engineering problems to solve. Chemical engineers have long been proficient at producing products that meet exacting specifications for chemical purity, but therapeutic proteins now bring additional challenges: these products must not only be highly chemically pure, but also conformationally pure, and must remain so after manufacturing through the drug’s entire shelf-life and delivery to patients. For economic viability, therapeutic protein formulations typically require a shelf life of 18-24 months. Over the course of this time the protein must retain adequate chemical and conformational purity. Meeting the stringent requirements for chemical and conformational stability during shelf life is a daunting task. Most of the common chemical degradation products (especially hydrolysis and oxidation byproducts) are significantly thermodynamically favored versus the desired native state of the protein. Furthermore, the properly folded native state of most proteins is only marginally more stable (the free energy of unfolding, ΔGunf, is about 20-60 kJ/mol) than the unfolded state, and appears to be unstable under most conditions with respect to aggregated forms of the protein.

To slow degradation sufficiently to allow proteins to be used as therapeutic agents, proteins must be placed in a formulation that confers suitable stability against physical and chemical degradation. In addition to stabilizing the pharmaceutically-active protein ingredients, formulation components, or excipients, also must be compatible with their intended use. For example, a formulation intended for parenteral use (e.g., subcutaneous injection) must be sterile, non-toxic and exhibit acceptable viscosity and tonicity. Although these requirements place limits on the types and concentrations of excipients that practically can be used, there are still far too many possible sets of formulations to allow a purely empirical screening approach to be used. The approach that our group takes is to explore fundamental mechanisms of processes that result in degradation and instability of therapeutic proteins. In particular, we use a number of spectroscopic techniques (e.g., FTIR, EPR, NMR, 2D-UV, LALLS, fluorescence spectroscopies) and physical techniques (e.g., analytical ultracentrifugation, titration microcalorimetry, field flow fractionation, mass spectrometry) to understand how solution variables (such as concentration and type of excipients, protein type and concentration, solution ionic strength) and process variables (e.g., agitation) interact to stabilize or destabilize proteins.

Immunogenicity of Protein Therapeutics: 

Therapeutic proteins are susceptible to aggregation in response to a wide variety of stresses encountered during their manufacture, storage and delivery to patients. In turn, aggregates of therapeutic proteins may compromise their safety and efficacy. The primary safety concern is that aggregates in therapeutic protein products may induce immune responses, which can have consequences ranging from reduction of product efficacy to patient fatality. Currently it is not well-known what characteristics of protein aggregates are responsible for immunogenicity. We are working to understand how nano- and microparticulate contaminants (including protein aggregates and exogenous microparticles resulting from processing) affect the immune response to therapeutic proteins. In these studies, we rely on physical and spectroscopic methods to characterize aggregate size and structure, and then test how animal models (usually naïve or transgenic mice) respond to parenteral administration of the aggregates.

A related area is our studies of protein-based vaccines. Vaccines offer tremendous benefit to human health, but creation of vaccine formulations that provoke a reliable, protective immune response in a formulation with adequate shelf life is a serious challenge. We are studying the stability of protein structure when adsorbed to relevant surfaces such as the aluminum phosphate salt microparticles that are currently used as adjuvants to enhance immune response.