eBooks

eBook: Development and Application of a Simple and One-Point Multiparameter Technique — Monitoring Commercial-Scale Chromatography Process Performance

In commercial-scale biopharmaceutical manufacturing, downstream chromatography steps are still a bottleneck and contribute to significant operational costs (1, 2). Some of those costs are inherent (e.g., resins, large buffer quantities, and cleaning) whereas others are avoidable (e.g., product loss due to rejected lots or deviations that result in production downtime). Maintaining efficient and robust chromatography process performance is therefore critical for minimizing operating costs. To do so, we introduce a simple and one-point multiparameter technique (SOP-MPT) for monitoring chromatographic process…

eBook: The Commercial Expression Systems Market — What Has Changed in the Past Decade

A decade ago, BioPlan Associates prepared the findings of its 2008 directory of expression system technologies that were being promoted or considered likely to be suitable for commercial licensing for biopharmaceutical manufacturing (1). Due in part to the relatively slow advances in this critical area of bioprocessing, this study remains perhaps the only directory of biopharmaceutical-relevant expression systems available for licensing. Here I discuss aspects of related bioprocessing technologies that have and have not changed in the past decade. Expression…

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

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:…

eBook: Innovations in CRISPR Technology — A Perspective on Research and Bioprocess Applications

One of the fastest growing areas in genome engineering is research using the powerful editing tool of clustered regularly interspaced short palindromic repeats (CRISPR). When paired with the Cas9 (CRISPR-associated protein 9), an RNA-guided DNA endonuclease enzyme from Streptococcus pyogenes, the site-specific prokaryotic immune system can be used to cut and manipulate DNA strands in cells of patients with genetic diseases to treat, or in some cases, prevent such diseases. Within the past couple of years, CRISPR has been shown…

eBook: Viral Vaccine Production — Cultivation of Vero Cells in Packed-Bed Bioreactors

Vero cells are anchorage-dependent cells that are used widely as a platform for viral vaccine production (1). In stirred-tank bioreactors, they are grown ordinarily on microcarriers. Fibra-Cel disks are an alternative attachment matrix because they provide a three-dimensional environment that protects cells from damaging shear forces. However, such disks have not been tested for the cultivation of Vero cells. We tested whether benchtop single-use and glass bioreactors with a packed bed made of Fibra-Cel disks would be suitable for cultivation…

eBook: Alternative Delivery of Biologics — Underdogs Pursue Roads Less Traveled

A number of failures in development of noninjectable delivery methods for therapeutic proteins have caused numerous development programs to crash and burn along with investors’ hopes, dreams, and cash. Most everyone reading BioProcess International is familiar with the issues and challenges: Needles hurt and involve risks to both caregivers and patients. Injections often require administration by trained personnel in specialized settings. But alternative delivery methods are fraught with greater challenges related to dosing, bioavailability (particularly for oral dosing), and inherent…

eBook: Development of a Representative Scale-Down UF/DF Model: Overcoming Equipment Limitations and Associated Process Challenges

Scale-down models (SDM) are physical, small-scale models of commercial-scale unit operations or processes that are used throughout the biopharmaceutical industry for validation studies, commercial deviation investigations, and postapproval process improvements. To support these studies, regulatory guidelines state that SDMs should be representative of the commercial process. For some downstream unit operations such as column chromatography, developing a representative SDM is straightforward because a linear scale-down approach can be used. However, developing a representative SDM for other downstream unit operations such…

eBook: Addressing Quality in Cell-Line Development — Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization

Using Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization Therapeutic monoclonal antibodies (MAbs) mostly are manufactured using bioengineered mammalian cells cultured in a bioreactor for two to three weeks. High temperatures and an altered redox environment may compromise the quality of MAbs produced (e.g., fragmentation, truncation), as can the presence of proteases, reductases, and other chemicals released from dead cells. Thus, it would be valuable to establish analytical methods that can help cell culture groups monitor immunoglobulin…

eBook: Of Microbrews and Medicines — Understanding Their Similarities and Differences in Bioprocessing Can Help Improve Yields and Quality While Reducing Cost

Meeting a biopharmaceutical scientist or engineer who proclaims a love for brewing is not surprising. Perhaps it’s because of the challenge of mixing raw ingredients together and waiting patiently for the final product, maybe it’s the hands-on nature of the equipment or the data analytics entertainment, or it just might be the simple joy of creating something. Whatever attracts a scientist or engineer to making medicines and/or craft brews, a surprising number of principles hold true for both bioprocesses despite…

eBook: Bioinks for Bioprinting — Three-Dimensional Printing in Research and Medicine

Three-dimensional (3D) printing is one method of digital biomanufacturing for both basic biological research and translational, clinical applications. The medical field has used it to create such constructions as 3D surgical models for preoperative planning, to assist surgeons in their procedure preparations, which improves postsurgical outcomes. Examples here include generation of cleft-palate models (1), orthopedic applications (2), and cardiovascular surgical planning (3). Other forms of 3D printing for biological applications — such as 3D bioprinting — go beyond such surgical…