CBER Expertise
Improvement of biological product quality by application of new technologies to characterize of vaccines and blood products: NMR spectroscopy and light scattering
Principal Investigator: Daron I. Freedberg, PhD
Office / Division / Lab: OVRR / DBPAP / LB
Overview
Public Health Issue: Complex biological products are difficult to characterize, making the manufacture of a consistent and predictable product more challenging. Incomplete characterization of vaccines and blood products increases the risk of inconsistencies in manufacture. These risks are especially high for novel products, where traditional methods may miss subtle and unanticipated variability in products. Biophysical methods such as NMR spectroscopy and light scattering provide an invaluable complement to the biological assays traditionally used to characterize these products. For example, small amounts of free polysaccharide in conjugate vaccine formulations that may greatly reduce the efficacy of these vaccines are most effectively detected with spectroscopic methods.
Regulatory Contribution: Development and evaluation of improved tests for licensed and candidate vaccine and blood product characterization using NMR spectroscopy and light scattering will improve the ability to consistently manufacture complex biological products.
Research Approach: Development and evaluation of new methods to characterize Anthrax and other bacterial vaccines by NMR spectroscopy, e.g., the detection of small amounts of free polysaccharide in conjugate vaccine formulations and precise measurement of anthrax protective antigen, lethal factor and edema factor within vaccine products.
Mission Relevance and Outcomes: Testing of vaccine and blood product samples and development of new technologies for physical characterization of complex biological products will aid in evaluating licensed vaccines and candidate vaccines such as AVA anthrax based on recombinant technology. For example, recently an adulterated vaccine was identified by NMR testing.
Publications
Proc Natl Acad Sci U S A 2007 Jul 10;104(28):11557-61
Extracellular structure of polysialic acid explored by on cell solution NMR.
Azurmendi HF, Vionnet J, Wrightson L, Trinh LB, Shiloach J, Freedberg DI
Anal Chem 2006 Jul 1;78(13):4634-4641
Chemical Characterization of Diaspirin Cross-Linked Hemoglobin Polymerized with Poly(ethylene glycol).
Buehler PW, Boykins RA, Norris S, Alayash AI
Dev Biol 2005;122:77-83
Using nuclear magnetic resonance spectroscopy to characterize biologicals.
Freedberg DI
Anal Chem 2005 Jun 1;77(11):3466-3478
Structural and Functional Characterization of Glutaraldehyde-Polymerized Bovine Hemoglobin and Its Isolated Fractions.
Buehler PW, Boykins RA, Jia Y, Norris S, Freedberg DI, Alayash AI
Carbohydr Res 2005 Apr 11;340(5):863-74
The utility of residual dipolar couplings in detecting motion in carbohydrates: application to sucrose.
Venable RM, Delaglio F, Norris SE, Freedberg DI
Proc Natl Acad Sci U S A 2005 Apr 12;102(15):5564-9
Escherichia coli K1 polysialic acid O-acetyltransferase gene, neuO, and the mechanism of capsule form variation involving a mobile contingency locus.
Deszo EL, Steenbergen SM, Freedberg DI, Vimr ER
J Am Chem Soc 2004 Aug 25;126(33):10478-84
Discriminating the helical forms of peptides by NMR and molecular dynamics simulation.
Freedberg DI, Venable RM, Rossi A, Bull TE, Pastor RW