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…

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…

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…

Host-Cell Protein Risk Management and Control During Bioprocess Development: A Consolidated Biotech Industry Review, Part 2

Even with increased understanding of host cell proteins (HCPs) and their potential risks, no practical approach has been made available for HCP risk management during bioprocess development. A BioPhorum Development Group (BPDG) team has identified common HCP-related risk factors and built a template for semiquantitative risk assessment during process development based on publicly available information. To this end, the BPDG HCP working team’s assay and knowledge-sharing experts have established a common HCP risk assessment tool and mitigation strategy to guide…

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…

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…

A Product–Packaging Interaction Study to Support Drug Product Development

Drug packaging is subject to a number of regulatory requirements, including those for product containers and packaging. For example, according to the federal Food, Drug, and Cosmetic Act (FD&C) section 501(a)(3), a drug is considered adulterated “if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health.” And 21 CFR states that drug packaging “shall not be reactive, additive, or absorptive so as to alter the safety,…

Large-Volume Wearable Injectors: A New Delivery Approach Could Change the Game

Biologic drugs are a driving force in the pharmaceutical industry. More than 2,700 were in pharmaceutical pipelines as of June 2017 to treat cancers (836), rare diseases (566), neurologic conditions (420), autoimmune disorders (311), and other ailments (567) — triple the number in 2013 overall (1). Biopharmaceuticals make up more than half of all drugs in development and are nudging out traditional small-molecule drugs rapidly while already bringing in billions of dollars in sales. The success of such drugs is…

eBook: The Future of Monoclonal Antibody Manufacturing — Incremental Improvement or Industrial Revolution?

Monoclonal antibody manufacturing is at a crossroads. Biomanufacturers could continue exploring new technologies and fine-tuning proven systems such as mammalian cell expression systems in stirred-tank bioreactor fed-batch cultures. But some experts say an opportunity is arising to turn the industry on its head by taking lessons from other branches of bioprocessing, such as the industrial enzyme sector. Drug makers are criticized often these days for the high prices of their products. The lay media, governments, payers, and patients themselves all…