Upstream Development

Cell Therapy Bioprocessing

          The past 15 years have seen approval and commercialization of the first cell-based therapeutics, including cartilage repair products; tissue-engineered skin; and the first personalized, cellular immunotherapy for cancer. Those successes are outnumbered, however, by all too common product failures. Notable failures can be attributed to commercial concerns such as high cost of goods (CoGs) and technical hurdles such as inadequate characterization, high process variability, and loss of product efficacy when manufacturing is scaled up (1).…

Linear Scale-Up of Cell Cultures

    Reusable bioreactors have been the benchmark standard for many decades, during which a large knowledge base on process control and scale-up has been developed. However, single-use bioreactors are increasingly being implemented in modern bioindustrial upstream processes. Many of these bioreactors deviate from the traditional stirred-tank design, but a number of companies have expressed a strong need for single-use bioreactors based on the strirred-tank design. A traditional stirred-tank design would enable users to optimize their scale-up processes based on…

Industrializing Stem Cell Production

Stem cells have potential as a readily available, consistent source of many differentiated cell types. This unique property can be leveraged both for therapeutic purposes and for facilitating and improving a number of drug discovery and development processes. Large-scale, “industrialized” production of human stem cells in tightly controlled conditions will be required to deliver the quantity and quality of cells needed to support clinical trials and drug discovery development activities (Figure 1). Achieving this level of production while meeting rigorous…

I’m Losing Cell Viability and Function at Different Points in My Process, and I Don’t Know Why!

    Development of cell and tissue therapies presents bottlenecks in manufacturing process development and scale-up as commercial and academic groups move from small-scale research and development (R&D) to more complex logistics. Often, the simplicity of maintaining cell yield, viability, and function in a laboratory setting cannot be replicated when source tissue and final therapeutic products are subjected to the extended distances and times of actual clinical delivery. These bottleneck issues have a number of causes. One specific and common…

Understanding the Basics of Peptide and Protein Production

With strong growth in biologics, large molecules, and biopharmaceutical therapeutics in recent years, the pharmaceutical and biotech industries are increasingly turning toward peptides and proteins in their search for drug discovery targets. While both offer significant therapeutic potential, there are fundamental differences between the two types of molecule. Definitions: Peptides are short polymers formed from the linking of (usually ≤100) amino acids. They comprise some of the most basic components of human biological processes, including enzymes and hormones. The link…

Is Bovine Albumin Too Complex to Be Just a Commodity?

    Albumin is the most abundant serum protein. It serves several functions in vivo: e.g., binding and transport of fatty acids, hormones, and metal ions; maintenance of osmotic pressure and pH; and binding of exogenous toxins and products of lipid oxidation (1). Over time, development of large–scale purification methods have translated those functions into diagnostic, cell culture, and microbiological applications. It is important to note, however, that purification procedures can promote molecular changes and thereby add to the already…

Process Development’s Impact on Cost of Goods Manufactured (COGM)

    Manufacturing throughput (the amount of material a plant can produce per year) is affected by process yield and plant run rate. The higher they are, the more a plant can produce per year, requiring fewer lots to meet annual demand. Although a process development team obviously determines the process yield, the team also determines the impact on the run rate of duration and potential implementation complexity of the entire train of unit operations. Thus, an optimized process maximizes…

Efficient Development of Stable High-Titer Cell Lines for Biopharmaceutical Manufacturing

Commercial manufacturing of therapeutic monoclonal antibodies (MAbs) commonly uses mammalian cells to generate large quantities of a drug. Identifying cell lines that stably produce high protein titers is, therefore, a critical part of biopharmaceutical development. Unfortunately, identifying suitable cell lines is traditionally a time-consuming, labor-intensive process. That’s because their productivity and stability can vary enormously, so large numbers of clones must be screened to find those with both the highest yield and a desired level of product quality (1). Cell-line…

Nutrient Supplementation Strategies for Biopharmaceutical Production, Part 2

Some of the numerous feeding strategies are more appropriate than others for certain types of cell culture production systems. Once a nutrient supplement has been identified as described in Part 1 of this three-part review (1), a supplementation strategy must be chosen. Supplementing at too great a rate may expose log-phase cells to stresses such as increased osmolality and lactate levels that would inhibit biomass expansion. But inadequate supplementation can lead to early apoptosis through rapid depletion of selected important…

The Need for a New Process

Surveying BPI readers’ experiences SANJA GJENERO (WWW.SXC.HU) Better, faster, safer: The current drug-development “paradigm” emerging from the FDA is pushing for innovations that reduce process inefficiency and cost. The plethora of new risk-based methodologies include tools being developed as process-analytical-technology (PAT) tools within the encircling parameters of a process design space. All this parallels (and drives) some predictions that the biotechnology industry has seen the last of its blockbuster models, as predictive genomic tools enable personalized approaches to therapeutic development.…