Analytical

Process Analytics and Intermediate Purification of Bispecific Antibodies with a Non-Affinity Platform

The therapeutic benefits of monoclonal antibodies (MAbs) have been demonstrated in recent decades with uncontestable success as treatments for human disease. Despite MAbs’ key features such as specificity, selectivity, and safety, the format has limitations (1, 2). Bispecific antibodies may overcome number of difficulties (3). Multiple formats of bispecific antibodies have been developed, although only the κλ-body is fully human and devoid of linkers or mutations. It requires no genetic modifications of heavy and light chains and results in bispecific antibodies…

Computational Science Changes Biolaboratory Design

Until relatively recently, life-science research was characterized by test tubes, Petri dishes, and centrifuges. Now, as with many industries, the life sciences are undergoing a digital transformation. Computational science is changing laboratory design. The healthcare industries always have generated large amounts of data. What has changed is the available information technology. With the growth of cloud computing, large data sets — and the high-speed tools for analyzing them — are available increasingly to a degree not possible with traditional servers…

Single-Use Sensors and Control and Data Acquisition Tools to Streamline Bioprocess Development

Process development and biomanufacturing in the biopharmaceutical industry have evolved extensively over the past 10 years. More tools are available to study process variables to enable more efficient and productive processes, speed development, and reduce costs. High powered microcontrollers are embedded in laboratory devices to carry out complex tasks. Recently, users have started working with microcontrollers such as Raspberry Pi for personal projects. As personal computer power has accelerated multiplefold,leading to high processing power and compact, high-capacity memory readily available…

Cell Culture Media: An Active Pharmaceutical Ingredient or Ancillary Material?

Cell-based therapies are used to treat diseases that require the replacement of diseased, dysfunctional, and injured cells (1). To produce these therapies, a wide range of reagents and materials such as antibodies, growth factors, and enzymes are used in their manufacturing processes. Such necessary materials are administered through a cell culture medium. Active pharmaceutical ingredients (APIs) are the main ingredients that make products therapeutic. Ancillary materials (AMs) and raw materials (RMs) are essential components used during production but are not…

Trends in Chemistry, Manufacturing, and Controls: Next-Generation Technologies and Product Modalities

New technologies bring new regulatory challenges. The biopharmaceutical industry must be cautious in its implementation of new scientific ideas and technology platforms — no matter how promising those might be. Regulators will look skeptically on any claim that isn’t backed up by good data, and with no solid history of successful use to build on, a company must have all the answers itself. How do compliance professionals anticipate what kinds of questions reviewers will ask when the time comes —…

Science Guiding Technology: Cell Line Development and Engineering 2018

Cell line development engineers in the biopharmaceutical industry juggle several, sometimes contradictory priorities. They must present their bioprocessing colleagues with a master cell line that can express a reproducibly high-quality protein product at titers and growth concentrations that will be high enough for manufacturing efficiency — and without those parameters degrading over time. Performing the first step in every bioprocess, these scientists must consider their own budgetary concerns and efficiencies while facing regulatory scrutiny under the 21st-century risk-management paradigm. In…

Myths, Risks, and Best Practices: Production Cell Line Development and Control of Product Consistency During Cell Cultivation

Health authorities are requesting substantial details from sponsors regarding practices used to generate production cell lines for recombinant DNA–(rDNA) derived biopharmaceuticals. Authorities also are asking for information about the clonality of master cell banks (MCBs) and control strategies to minimize genetic heterogeneity. Such requests are prompted by recent reports indicating “nonclonality” for certain production cell lines. To address these and related issues, the CASSS CMC Strategy Forum on “Production Cell Line Development and Control of Product Consistency During Cell Cultivation:…

Rapid Generation of High-Producing Clonal Cell Lines: Using FRET-Based Microfluidic Screening for Analysis, Sorting, Imaging, and Dispensing

Sales of monoclonal antibodies (MAbs) are predicted to be over US$125 billion by 2020 (1). Such revenue potential puts significant pressure on the biopharmaceutical industry to reduce timelines, especially to first-in-human trials. Cell-line development represents a large and critical portion of the early development timeline. Whether a developer is using random or targeted integration for introducing genes into a host-cell genome, the regulatory requirement for addressing monoclonality introduces a time and resource-intensive step in this process. Many different techniques are…

Dye Ingress Methods for Container–Closure Integrity Testing: An Industry Position Paper

The primary goal of container–closure integrity (CCI) is to maintain the sterility and product quality of parenteral biopharmaceuticals throughout their shelf life and use. Guidelines detailing the initial CCI qualification and validation requirements have been defined and can be found in the US Pharmacopeia chapter 1207 (USP<1207>) (1). The guidelines described in USP<1207> can be applied to any common CCI testing (CCIT) method to achieve a method suited for its intended use within a drug product lifecycle. CCI is not…

Big Biotech Data: Implementing Large-Scale Data Processing and Analysis for Bioprocessing

Managing large amounts of data presents biopharmaceutical companies of all sizes with the need to adopt more efficient ways to handle the ongoing influx of information. At KNect365’s September 2017 Cell and Gene Therapy conference in Boston, Lisa Graham (founder and chief executive officer of Alkemy Innovation, Inc. in Bend, OR) spoke about the need for data management, data analysis, and process monitoring systems to evolve. Although she was speaking at a cell therapy event, her points are applicable to…