Biomedical Engineering Reference
In-Depth Information
TABL E 3.4. Select Critical Process Parameter and CQAs of Recombinant Malarial Drug
Substances Manufactured at Pilot Scale for Phase I Human Clinical Trials
Critical Process or
Quality Attribute
Outcome
Manufacturable process
Identified approach using P. pastoris
for scalable production
Acceptable quality
Absence of N-linked glycosylation
Limited O-linked mannosylation
Structural integrity
Induction of inhibitory antibodies
Acceptable quantity
>
20mg/L or
1000 doses/L broth
Overexpression of PDI
Improved profile for all of the above
and reduction of O-linked mannosylation
ACKNOWLEDGMENTS
The work on expression and production of EBA-175 was performed by the Malaria
Group at EntreMed, Inc., Rockville, MD. The Malaria Group was led by Dr. David
Narum, Associate Director, and its members were Steve Fuhrmann, SteveMerchant, and
Jennifer Wingard, along with Hong Liang from Molecular Biology and Dr. Tom Chen
from Pharmaceutical Sciences. The Malaria Group was directed by Dr. B. Kim Lee Sim,
Vice President, Preclinical Development. I also thank Dr. Louis Miller from the Malaria
Vaccine Development Branch, DIR, NIAID, NIH, for providing the yeast-encoded
synthetic gene sequence of AMA1-3D7. I appreciate the help of Drs Louis Miller,
Matthew Plassmeyer, Laura Martin, and Mr. Richard Shimp for their critical review of
the chapter. The EBA-175 project was funded in part with Federal funds from the
National Institute of Allergy and Infectious Diseases, National Institutes of Health, under
Contract No. AI-05421.
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