Manufacturing

Tracking Therapeutic Antibody Development in a Pandemic

The COVID-19 pandemic has generated a significant and rapid response from scientists who aim to develop drugs and vaccines in the academic, government, and industrial sectors. Such interventions are essential to containing SARS-CoV-2, the coronavirus that causes the COVID-19 disease. To inform and educate the public about global efforts to develop targeted therapies such as monoclonal antibodies (MAbs), The Antibody Society (TAS) and the Chinese Antibody Society (CAS) have designed and implemented a freely available online database called the COVID-19…

G-Protein–Coupled Receptors: Promising Targets for Antibody–Drug Conjugates

G-protein–coupled receptors (GPCRs) are a large and diverse family of seven-transmembrane–domain proteins expressed on the surface of human cells. These molecules respond to external stimuli by initiating signal-transduction pathways that affect the expression of a large family of genes — which, in turn, regulate a range of vital physiological processes and functions. Figure 1 illustrates the general pathways of GPCRs. Without these proteins, humans simply could not survive: Without β-adrenergic receptors, we could not regulate our blood sugar, for example;…

Next-Generation Biotechnology Product Development, Manufacturing, and Control Strategies, Part 1: Upstream and Downstream Strategies

Future biomanufacturing must address industry drivers, including the need for decreasing cost of goods (CoG), increasing market globalization, shortening development time for pipeline products, reducing risk to patient supply, and improving product quality. A CASSS chemistry, manufacturing, and controls (CMC) forum entitled “Next-Generation Biotechnology Product Development, Manufacturing, and Control Strategies” took place on 16–17 July 2018 in Gaithersburg, MD, to address those opportunities. Advanced technologies include single-use bioreactors, alternating tangential-flow (ATF) systems used during fermentation, modular and closed process equipment,…

Run Rules with Autocorrelated Data for Continued Process Verification

Control charts can be used to assist in monitoring of biopharmaceutical product quality attributes as part of continued process verification activities. A number of tests known as run rules have been developed to assess whether biomanufacturing processes remain in statistical control. In practice, results for such attributes can be positively autocorrelated. Simulated data are used to assess the performance of run rules with autocorrelated data to assist in determining risk–reward profiles for process monitoring. Autocorrelated Data The tendency for data…

Technology to Transform AAV Manufacture

Adenoassociated virus (AAV) vectors are a popular choice for modern gene therapies because of their favorable safety profile, low immunogenicity, and the ease with which they can be transduced into different cell and tissue types. An AAV genome is a single strand of DNA comprising a replication (rep) gene, which encodes regulatory proteins involved in genome replication, and a capsid (cap) gene, which produces three capsid proteins. However, AAVs cannot replicate alone. In nature, AAV shares an exquisite relationship with…

eBook: Antibody–Drug Conjugates — Refining Product Designs for Improved Outcomes

Antibody–drug conjugates (ADCs) seek to partner the target specificity of antibodies with the cell-killing punch of chemotherapy drugs. Researchers identify antibodies that bind to proteins found predominantly or exclusively on the surfaces of cancer cells. The cells can absorb the ADC into their interiors, where the chemical environment or enzymes detach the drug from the antibody, freeing it to wreak havoc. Although nine ADCs have received US Food and Drug Administration (FDA) or European Medicines Agency (EMA) approval (and many…

eBook: Trends in Facility Design — In-House Manufacturing Considerations for Cell and Gene Therapy Production

Manufacturing and facility challenges facing cell and gene therapy companies are similar to but more complex than those encountered by companies that produce traditional biopharmaceuticals such as vaccines, monoclonal antibodies, and other therapeutic proteins. A single product can have multiple components, manufacturing of which may or may not be outsourced. Project timelines are short, production technologies are new and evolving, and clinical demands change rapidly. Increasing competition for contract manufacturing services requires reserving capacity far in advance, which in most…

Unraveling the Complexities of Technology Transfer

In the biopharmaceutical industry, technology transfer refers to transfer of any process, together with its documentation and professional expertise, between development and manufacture or between manufacturing sites (1). This operation is common in the biopharmaceutical industry for a number of structural reasons. They include the dichotomy between small, innovation-based drug companies and large ones able to conduct late-phase clinical development and endowed with manufacturing capacity; the high capital cost of biopharmaceutical plants, which makes contract manufacturing attractive; and the need…

Developing Advanced-Therapy Products Through Global CDMOs

Tremendous growth in the cell and gene therapy (CGT) industry is driving unprecedented demand for manufacturing services. To be sure, advanced-therapy developers increasingly are choosing to install in-house capabilities. Doing so can offer companies greater control of their processes, timelines, and budgets than they might have when outsourcing products (1). But industry experts agree that contract development and manufacturing organizations (CDMOs) will remain integral to CGT manufacturing and commercialization (1, 2), especially with veteran contract partners scrambling to acquire CGT…

Dissolved Oxygen Control Tuning for Cell Culture Applications

Proper tuning of dissolved oxygen (DO) controller proportional integral (PI) values is essential for optimal cell culture performance in a bioreactor. When DO-PI values are optimized, gas flows are smoothed, and foaming and cell stress are reduced. Traditionally, this tuning has been performed by using nitrogen gas to purge oxygen from a test solution, thus simulating oxygen demand. That method has several drawbacks, however. First, nitrogen gassing cannot simulate the high demands of high-density fermentation. Second, nitrogen competes with other…