Analytical

Better Bioprinting Ahead: Breakthroughs and Remaining Challenges

Bioprinted organs soon could revolutionize clinical trials, transplantation, and regenerative medicine. But as Chris Lo reminds us in a new GlobalData report (1), several technical hurdles must be negotiated before biopharmaceutical companies can harness three-dimensional (3D) bioprinting for such purposes. BPI explores persistent printing problems and promising solutions below by analyzing Lo’s report alongside commentary from founding editorial advisory board member Bill Whitford (bioprocess strategic solutions leader at GE Healthcare Life Sciences), Lev Gerlovin (vice president in the life sciences…

eBook: Sensor Technologies — Essential Tools for Bioprocessing 4.0

Sensors are essential devices that can be used for most, if not all, typical biopharmaceutical development and manufacturing processes to monitor fundamental process parameters such as flow, temperature, pH, and dissolved oxygen throughout all process stages. As the bioindustry progresses toward automation, digitalization, and other “Manufacturing 4.0” concepts, robust single-use and smart sensors for bioprocess monitoring will be needed. Read this BPI eBook to garner valuable perspectives on both of these types of sensors. Discussions herein focus on smart sensor…

Evaluating Biosimilars: A View from the Small-Molecule World

For many years the pharmaceutical industry was dominated by small (usually synthetic) molecules, mixed with a number of nonactive materials and encapsulated or (in the really old days) rolled into pills or pressed into tablets. Although synthesizing the active pharmaceutical ingredients (APIs), formulating the dosage forms, and analyzing the materials at every stage of a product life cycle were not always trivial activities, they were relatively straightforward. Most of the tools needed for analyzing/controlling each step of the manufacturing process…

Bioassay Evolution: Finding Best Practices for Biopharmaceutical Quality Systems

Bioassays help drug developers determine the biological activity (potency) of their products, which has been a biopharmaceutical critical quality attribute (CQA) since long before that concept had a name. Because of their complex nature, bioassays are among of the most challenging experiments to perform reliably with dependably accurate results. Consistent assay performance requires a controlled environment and qualified reagents; skilled analysts who understand cell physiology, regulatory requirements, and the latest techniques; and assay protocols that are intelligently developed, characterized, and…

Biopharmaceutical Product Specification Limits and Autocorrelated Data

Calculations, including statistical tolerance intervals, can assist in the development and revision of specification acceptance criteria. Manufacturing results for attributes of a biopharmaceutical product can be positively autocorrelated. The sample standard deviation — calculated from limited, positively autocorrelated data — tends to underestimate the long-term process standard deviation (1). In this article, simulated data are used to assess the relative performance of statistical tolerance intervals, intervals calculated using the minimum process performance index Ppk approach, and the sample range. Prevalence…

Bioprocess Development and Qualification: PAT-Based Stage 1 and 2 Acceleration Strategies

Well-established process analytical technology (PAT) strategies, such as those based on spectroscopy, bring with them several challenges related to the nature of those tools themselves (1–3). Such tools are multiparametric by design — in the sense that most spectroscopies capture multiple attributes sometimes different in nature (e.g., near-infrared, NIR, captures chemical and physical attributes simultaneously). Often a reference method is required; at other times, indirect calibrations are based on the correlation of one culture attribute with another for which a…

Ask the Expert: Cell Culture Media Analysis Using Handheld Raman Analyzers

In biopharmaceutical manufacturing, cell culture media supply critical nutrients and maintain pH and osmolality to optimize protein product yield. Because media composition and condition have a strong effect on final biologic product quality and production, biopharmaceutical companies monitor media for lot-to-lot variability. Stability testing for degradation due to light exposure, temperature changes, or shelf-life/time is possible with rapid spectroscopic methods. In an 8 October 2019 “Ask the Expert” webinar, O. Dean Stuart (product manager at Thermo Fisher Scientific) explained how…

Trends in Data Analytics As Organizations Undergo a Digital Transformation

The biopharmaceutical industry is in the midst of an exciting transformation as biologics experience massive growth — even outpacing the small-molecule segment (1). Biologics are predicted to comprise over a quarter of the pharmaceutical market in 2020 (2). At the same time, a plethora of new biologically derived therapy concepts — e.g., cell and gene therapies — are in development. Some biologics classes have become mainstream — e.g., monoclonal antibodies — with biosimilars entering the market and contract manufacturing organizations…

Detection and Clearance of Viruses in the Biopharmaceutical Industry

Viral contamination is a common threat to all animal- and human-derived biopharmaceuticals. This type of contamination can affect any part of a bioproduction process, so biomanufacturers need to perform viral testing studies and incorporate viral clearance methods into their processes. Viral contaminants can come from cell lines (e.g., endogenous retroviruses) or from adventitious (e.g., mycoplasma) introduction during drug manufacturing. Virus testing of master cell banks (MCBs), working cell banks (WCBs), end-of-production cell banks, and bulk unprocessed harvest material is called…

Analytical Testing Strategies for CAR T-Cell Products

Assay lifecycle development for traditional biopharmaceuticals such as vaccines and monoclonal antibodies (MAbs) has a clearly defined pathway, from preclinical method selection, development, and optimization through the milestones in preclinical phase trials, and finally to postlicensure method evaluations, comparability, and improvements. The analytical development roadmap for nontraditional biologics such as chimeric antigen receptor (CAR) T-cell therapies and gene therapies are not as clearly defined and can present many challenges along the way. Understanding the “what, how, and when” of analytical…