Engineering Commons^™

Biophysical Characterization Approaches To Aid The Selection Of Protein Formulations By Predicting Their Physical Stability During Long-Term Storage, Hristo Svilenov, Gerhard Winter

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

The formulation of therapeutic proteins is a critical process which aims at finding the most suitable conditions that impede protein degradation during long-term storage. One degradation path of high interest is the non-native aggregation¹. The latter can be greatly suppressed by the selection of suitable solution conditions². Over the years, various biophysical techniques have been explored as tools to quickly select the most promising formulations for long-term storage.

In this talk, we share the experience in our lab how some of these techniques can be integrated into protein formulation studies. We discuss the application of differential …

A Novel Technique To Characterize The Surface Hydrophobicity Of Proteins Using Inverse Liquid Chromatography, Dilip Sethi, Sarah Hedberg, Daryl Williams

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

This work presents a novel technique to characterize the surface hydrophobicity and other surface properties of proteins. The surface properties of industrial and therapeutic proteins are key to understanding their behavior in-situ, in the laboratory and in processes. Protein surface hydrophobicity is a marker for three dimensional structure, stability and function. Inverse Liquid Chromatography of Proteins (ILCP) with small molecule hydrophobic probes can be used to obtain direct measurements of the surface hydrophobicity of column resin-bound proteins using changes in probe retention behavior. The dimensionless hydrophobicity factor (H_f) for Lysozyme and BSA was obtained with changing pH …

Aggregation Challenges In The Formulation Development Of Multi-Dose Peptide Products, Jingtao Zhang, Katelyn Smith, Wei Xu, Yongchao Su, Suzanne D’Addio, Yogita Krishnamachari, Jameson Bothe, Daniel Yin, Xinpei Mao

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

The formulation development of parenteral peptide therapeutics frequently encounters aggregation challenges. In-depth biophysical understanding of the molecule and formulation are required to achieve formulation robustness. Further, unique considerations need to be given for peptide products that require multi-dose as the use of preservatives can promote aggregation while preservative effectiveness can also be impacted by its interaction with the peptide. This presentation will focus on the reversible and irreversible fibril aggregates in peptide formulations. Biophysical characterization of aggregation and formulation will be discussed in detail. Formation of reversible aggregates and the impact of excipients especially preservatives will be discussed. For the …

Conference Program, Samiul Amin, Paolo Arosio, Miguel Rodrigues

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

No abstract provided.

Conference Program, Erin Buckley, Christophe Moser, Brian Pogue, David Sampson

Advances in Optics for Biotechnology, Medicine and Surgery XVI

No abstract provided.

Novel Supply Chain And Process Modeling For Cell Therapy Manufacturing And Distribution, Chip White, Ben Wang, Kan Wang, Reid Bishop, Aaron Levine, Brian Liu, Bhavya Divvela, Aubrey Incorvaia, Kris Saha, Tava Das

Advancing Manufacture of Cell and Gene Therapies VI

We present a two-level hierarchical supply chain model of (autologous) CAR-T cell therapy that serves as the basis for the development of strategies to: 1) deliver cell therapy products that are safe and have a high level of efficacy, 2) minimize fulfillment time and variability, and 3) reduce total manufacturing and logistics costs while reducing the risk of patient morbidity and mortality. The model consists of two integral components: (1) an agent-based program for a “single manufacturing facility” that simulates the manufacturing and quality control process of cell therapy; and (2) a supply chain network program that evaluates different supply …

Key Engineering Challenges In The Biomanufacturing Of Lentiviral Viral Vectors, Peter Jones

Advancing Manufacture of Cell and Gene Therapies VI

No Abstract.

Tangential Flow Filtration And Scalability In Viral Vector Purification, Eni Sterjanaj, Heather Mall, Rachel Legmann, Jacky Dang

Advancing Manufacture of Cell and Gene Therapies VI

Pall Biotech has linearly scalable tangential flow filtration technology that can cover processing volume ranges from less than a liter to over 2000 liters. Manual assemblies can be used with Pall TFF filters in scales under 20L and programmable skids are available for larger scales. In this document TFF linear scalability of up to 200 liters is covered starting from a 7L initial volume and maintaining similar pressures, processing times and yields at all scales. Using this scalable technology Pall biotech can help biologics companies go to clinical trials and to commercial scale manufacturing successfully.

Please click Additional Files below …

Single Use Disposable Biosettler Removes The Dead Cells And Cell Debris Selectively To Increase The Viability Percentage Of Mammalian Cells (E.G., Car-T) During Expansion, Dhinakar Kompala

Advancing Manufacture of Cell and Gene Therapies VI

Current challenge in a FDA approved cell therapy product for adult B-cell leukemia is reported to be the percentage of viable cells after manufacturing is sometimes out of specified range. As the head of a large contract development and manufacturing organization observed, this fall in viability percentage during CAR-T cell manufacturing is a challenge to the whole industry.

We present a simple and powerful off-the-shelf solution to this big challenge in all mammalian cell culture expansion bioreactor system. Our single use disposable BioSettler has been demonstrated to be uniquely capable of removing dead cells and cell debris selectively from the …

Conference Program, Dolores Baksh, Rod Rietze, Ivan Wall

Advancing Manufacture of Cell and Gene Therapies VI

No abstract provided.

Development Of A Closed Car-T Manufacturing Process, Loo-Yong Steven Kee, Calley Hirsch, Devina Ramsaroop, Elizabeth Csaszar, Danylo Sirskyj, Aaron Dulgar-Tulloch

Advancing Manufacture of Cell and Gene Therapies VI

The field of immunotherapy has emerged as a promising new type of treatment for cancer with the approval of the first two CAR-T therapies. The clinical success of T-cell based immunotherapies necessitates a robust manufacturing process for these products to be consistently produced at commercial scale. Our CAR-T workflow combines unit operation specific solutions for thaw of an apheresis unit, wash, CD3 selection, T-cell activation, lentiviral transduction, incubator- and reactor-based expansion culture, harvest, formulation, cryopreservation and thaw of CAR-T product. We have evaluated the impact of both serum-containing and xeno-free culture media, commercially available T-cell selection and activation reagents, closed …

Workshop Agenda, Fernanda Masri

Advancing Manufacture of Cell and Gene Therapies VI

No abstract provided.

Scale-Up Study For Ex-Vivo Expansion Of Allogeneic Natural Killer Cells In Stirred-Tank Bioreactor, Juyoung Kim, Hyung Jin Nam, Sang Hyun Lee, Jong Beom Ku, Seung Ryel Han, Hye Jin Shin, Yu Kyeong Hwang, Sang Hoon Paik

Advancing Manufacture of Cell and Gene Therapies VI

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be …