(340bw) Three Biotherapeutic Case Studies: Manufacturing, Analytical Characterization, and Delivery | AIChE

(340bw) Three Biotherapeutic Case Studies: Manufacturing, Analytical Characterization, and Delivery


Ramesh, S. - Presenter, North Carolina State University
Smith, R., North Carolina State University
Gorman, C., North Carolina State University
Daniele, M., NC State University UNC Chapel Hill
Menegatti, S., North Carolina State University
Biomolecular medicine has revolutionized human therapy. Currently, three grand families of drugs coexist in the market: small molecule drugs, proteins, and viral vectors for gene therapy. Each comes with unique challenges: (i) small drugs must be safely released through controlled mechanisms that supplement a sustained flux of drug localized at the therapeutic site; (ii) protein-based drugs like monoclonal antibodies (mAb) must be carefully characterized in terms of purity, and structural and biochemical potency; (iii) viral vectors for gene therapy must be produced in small to medium scale productions that meet the clinical demand for patient and disease-specific applications. In my doctoral work, I have conducted research addressing these three key topics to address their limitation in the biopharmaceutical space.

Expression and purification of trans-gene carrying Adeno-associated viruses for gene therapy: My collaboration with the process development group at BridgeBio Pharma involved the optimization of bioreactor conditions that lead to the increase in viral particle titer above 109 vp/mL. We also worked on the affinity capture of the viral vectors using commercial and novel affinity adsorbents, focusing on improving the viability of the product by optimizing operational parameters governing the elution steps. To cater to one of the most pressing purification questions regarding identifying full vs. empty capsids, I worked on developing a process analytical technique to quantify their separation efficiency in HeLa cultures.

Sustained and controlled release of antibiotics: A novel class of dendrimers called DendriPeps featuring a poly(amidoamine) (PAMAM) backbone hybridized with peptide segments was synthesized as a means to encapsulate poly(N-isopropyl acrylamide) [PNIPAm]-based microgels to create a coating that is reconfigurable in response to shear stress [1,2]. The shear-responsive nature of this encapsulation system was quantitatively investigated using innovative experimental techniques, and the shear rates were assigned to the disassembly of the DendriPep coating. The shear-responsive nature of the DendriPep on drug loaded microgels was used to build shear-responsive peptide delivery vehicles. The reversible encapsulation and detachment of the DendriPep coating on the microgels regulated the rate of release of antibiotic peptides from microgels coated with DendriPeps via the modulation of the shear imparted to the composite.

Miniaturized biosensors for in-line monitoring of critical quality attributes of therapeutic antibodies: Our group has developed multi-array QCM-based sensors for scalable, in-line, and real-time analysis of mAb (total concentration, structural integrity, glycosylation, and aggregation), and CHO HCP quantification. The total concentration of different mAbs will be analyzed using Protein A as the biorecognition agent. The regenerability and the reusability of the sensor will be evaluated, and its performance will be compared to at-line/off-line commercial assays.


[1] Smith, R. J.; Gorman, C. B.; Menegatti, S. DendriPeps: Expanding Dendrimer Functionality by Hybridizing Poly(Amidoamine) (PAMAM) Scaffolds with Peptide Segments. Macromol. Rapid Commun. 2019, 40, 1900325.

[2] Smith, R. J.; Fabiani, T.; Wang, S.; Ramesh, S.; Khan, S.; Santiso, E.; Silva, F. L. B.; Gorman, C.; Menegatti, S. Exploring the Physicochemical and Morphological Properties of Peptide‐hybridized Dendrimers (DendriPeps) and Their Aggregates. J. Polym. Sci. 2020, pol. 20200277.

Research Interests: biosensors, drug delivery, process development


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