Manufacturing

eBook: Manufacturing CAR-T Cell Therapies — Insights and Challenges

The rapid evolution and clinical success of T-cell immunotherapies is an exciting advance in the war on cancer. This treatment modality uses engineered cells from a patient’s own immune system to target and destroy cancerous cells. Chimeric antigen receptor T-cell (CAR-T) therapy is emerging as the most studied treatment in T-cell immunotherapy and is the basis for many ongoing clinical trials. FDA approval of the first two CAR-T therapies in 2017 provides a regulatory development framework, but optimization of CAR-T…

Accelerating Intensified Bioprocesses with High-Throughput Small-Scale Tools

While many biopharmaceutical companies are exploring paths toward continuous processing, many tools already exist for implementing process intensification. As the authors of this special report illustrate, hybrid continuous processes that benefit from single-use technologies along with continuing improvements in perfusion cell culture already now are enabling improvements in cost reduction and accelerating time to market. And novel high-throughput and automated small-scale systems are helping development scientists gather more information in less time than before, reduce their development footprints, and make…

Oxygen Mass Transfer Correlation for a Rocking-Motion Bioreactor System

Disposable bioreactor systems are technologies commonly used in bioprocessing. They provide cost-effective contamination control and allow more flexible facility layouts than do stainless steel alternatives. One of the most popular types of single-use bioreactors uses a rocking platform in place of a traditional shaft and agitator assembly to aerate and mix cell culture material within a presterilized, single-use plastic bag (1). The system studied here is the ReadyToProcess WAVE 25 bioreactor (GE Healthcare Life Sciences). In contrast to conventional stirred…

Demonstrating Scalable T-Cell Expansion in Stirred-Tank Bioreactors

Emerging cell therapies have excited the pharmaceutical industry because they indicate potential new pathways to treat some of the most life-threatening diseases. T-cell therapies currently are the flagship technology in cell therapy with recent US FDA approvals of Novartis’ Kymriah (tisagenlecleucel) and Gilead’s Yescarta (axicabtagene ciloleucel) treatments. Those therapies and others still in development use peripheral blood isolated lymphocytes (PBLs) modified with chimeric antigen receptors (CARs) or modified T-cell receptors (TCRs) to trigger the innate cytotoxic response of these immune…

Single-Use Bioreactors: Performance and Usability Considerations Part 1: Performance for Process Control

There is ever increasing pressure for the biopharmaceutical industry to drive toward higher efficiency and lower costs. Compared to the past, target markets for many drugs typically are becoming smaller, and so-called blockbuster drugs are becoming more the exception than the rule. Regulatory agencies have continued to increase the pressure on drug makers to meet increasing quality standards and accept higher levels of responsibility. Furthermore, customer pricing, healthcare markets, and recent biopharmaceutical pricing scandals all add incentives toward more efficient…

Accelerating Vaccine Production Using a Nonviral Enabling Technology for Cell Engineering

At the recent World Vaccine Conference, Victor Ayala, PhD, an early stage investigator with Advanced BioScience Laboratories, Inc. (ABL), discussed how to accelerate vaccine production using a nonviral enabling technology for cell engineering. ABL is a contract research/manufacturing organization (CRO/CMO) providing manufacturing and laboratory research services to advance leading vaccines and therapies from clinical development to the commercial market. The company has been conducting R&D research for over 55 years and performing CMO manufacturing for over 25 years. With more…

Cultivating Better Working Relationships with Contract Manufacturing Organizations: A Panel Discussion

On 21 March 2018, a panel discussion during BPI West in San Francisco addressed ways to improve working relationships between sponsors and contract manufacturing organizations (CMOs). Our goal as organizers was to avoid retreading overfamiliar ground: Many outsourcing articles stress the importance of good communication without delving into actual strategies for improvement. So I asked the panelists to focus on the word better and what that actually means in this context. The most productive way to approach such a discussion…

Dual Sourcing of Protein A Resin to Mitigate Supply Chain Risk: A Comparative Study to Determine Equivalence

Protein A affinity chromatography is a well-established technology that is used extensively for large-scale purification of monoclonal antibodies (MAbs). With this mode of chromatography, very high product purity can be achieved in a single, relatively simple unit operation. A solution containing the target protein of interest is applied to a liquid-chromatography column at near-neutral pH, and one or more wash steps follow to lower product- and process-related impurities (1). Product is eluted through application of a low-pH buffer. Finally, the…

Innovators and Biosimilar Companies: Experts Predict Intense Conflicts Ahead

CPhI Worldwide (organized by UBM) announced last fall the final section findings of the fifth edition of the CPhI Annual Report. Presented live at the meeting in Frankfurt, Germany, the report is now available online. It highlights immediate and long-term trends in pharmaceutical data, regulation, generics, and biosimilars. Four experts gave their views. They warned that the US Food and Drug Administration’s (FDA) approach to achieving six-sigma (nearly perfect or 99.9997% defect-free) quality is failing in respect to the pharmaceutical…

eBook: SUStainability — Concerning Single-Use Systems and the Environment

Disposable materials have been used in many aspects of biomanufacturing since muromonab was first launched in 1986. Single-use stirred-tank bioreactors first became commercially available from HyClone in 2004 (1). Despite their demonstrated value to bioprocessing, disposable materials remain the subject of wide-ranging differences of opinion. Discussions of any technology are healthy and important for identifying areas for improvement, but some hearsay and bold propositions made regarding single-use components and the environment are not always helpful. Sustainability is an important and…