Information Technology

Decision-Support Tools for Monoclonal Antibody and Cell Therapy Bioprocessing: Current Landscape and Development Opportunities

Industrial-scale manufacturers in a number of fields — from automobiles to biotherapeutics — have long relied on powerful computational and mathematical tools to aid in the scale-up, optimization, quality control, and monitoring of product development (1–5). Typical process pathways are highly multifactorial, with numerous branch points, feedback steps, instrumental attributes, and target parameters. Moreover, margins for error are minimal for most industrial processes, requiring high standards of precision from industrial and operational pathways (6). For those reasons, the complexity of…

Information Instead of Data: User-Friendly HMI Concept Increases Process Control Efficiency

Today, most plant operators are much more than classic process operators. In addition to operational process control, their range of tasks includes product quality assurance, optimization of resources, and maintenance of high‑throughput rates. Qualified information is necessary to reliably perform those tasks. The human–machine interface (HMI) of a process control system provides visualization. Siemens regards new HMI concepts such as advanced process graphics (APG) as the key to task‑specific or situation‑specific decision‑making (Photo 1). Graphics Monitor: the Process Window Before…

Outsourced Data Integrity: Are Short-Term Financial Gains Worth Long-Term Headaches?

Competitive pricing and continued cost pressures have contributed to the need for many US biopharmaceutical companies to outsource manufacture of active pharmaceutical ingredients (API) and finished products from countries with lower costs for labor, material, and equipment. The main benefit of doing so is lower costs of manufacturing with quality standards comparable to those found in the United States. India and China now account for 80% of API production. But those countries have received media attention because of biopharmaceutical manufacturing…

Bioconjugation Reaction Engineering and Kinetics Simulation

Bioconjugates represent an important and growing class of pharmaceuticals that include PEGylated proteins, vaccines, and antibody-drug conjugates (ADCs) (1–8). Numerous protein conjugation techniques exist (9). Among the more important conjugation chemistries used for protein therapeutics are N-hydroxysuccinimide (NHS), aldehyde, and maleimide (10–13). To date, process development of industrial biopharmaceutical conjugation reactions has largely been empirical in nature. Typically, many experiments testing different reaction parameters are required to identify optimal process conditions. In some instances, nonmechanistic statistical models can be used,…

Managing Collaboration Across the Extended Organization

In an increasingly competitive life-science landscape that includes numerous mergers, acquisitions, and changing business models, the demand for collaboration is increasing at such a pace that it exceeds information technology (IT) capabilities. The need to manage and control this collaboration across the supply chain has become mandatory. That is particularly true for larger organizations with hundreds or thousands of partners that are finding new ways to connect, interact, and conduct business. Individual businesses are forming contractual affiliations that extend beyond…

Analytics for Modern Bioprocess Development

Twelve years ago, about the same time the US Food and Drug Administration was putting the finishing touches on its quality by design (QbD) and process analytical technology (PAT) guidelines, I wrote an article about breakthrough pharmaceutical educational programs. That article included the perspectives from a few members in academia of the future essential skills for pharmaceutical students. At the time, bioinformatics and computerized industrial process modeling were relatively new disciplines, but their importance in future manufacturing was clear. Several…

Analysis By Size and Charge

An early BPI Lab article addressed the power of liquid chromatographic separations for biopharmaceutical laboratory use (1). Such techniques separate biomolecules based on a number of different properties: size, solubility, hydrophobicity/-philicity, binding affinity. The next most powerful means of separation — and thus high-resolution identification — of nucleic acids and proteins/peptides is based primarily on electrostatic properties: electrophoresis. Although it doesn’t really work in a process or preparative setting, it is a fundamental technique in modern biopharmaceutical laboratories, where it…

Advances in Sensor Technology Improve Biopharmaceutical Development

Today’s biomanufacturing operations require constant management of biopharmaceutical process attributes throughout process development and production. Continuous online measurements of pH, dissolved oxygen (DO), oxidation–reduction potential (ORP), and conductivity (Figure 1) allow real-time industrial process monitoring and adjustment. These functions are crucial to process improvement studies and accurate, reliable manufacturing of high-quality products. Figure 1: () “In the pharmaceutical industry, it is extremely valuable to see how an attribute changes with time and correlate that change with parts of the process,”…

Manufacturing Culture

Life sciences company leaders need to put the right people, processes, and technologies in place to create evolutionary cultures. Such cultures would embrace advanced manufacturing process intelligence and reap related business benefits. Since the late 1990s, my software company has helped biomanufacturers improve their process understanding. In that time, we’ve seen regulatory drivers such as quality by design (QbD) and process analytical technology (PAT) guidances call for improved manufacturing process performance through better process understanding and optimization. We define process…

A Framework for Process Knowledge Management

    Process development and manufacturing for biopharmaceuticals are often disjointed activities. Disconnects between groups within an organization can be aggravated by a lack of common terminology and poor data-management practices. Implementing a simple data model based on the ISA-88 standard for batch control can help companies capture process and facility data throughout their product life cycle (1). The first half of this two-part article illustrates how translating a process description to a structured electronic format could transform the bioprocessing…