This article proposes a “design space” structure for using Quality by Design (QbD) to develop processes and control strategies for developing and manufacturing biopharmaceuticals…
The cell therapy industry is positioned to make major changes in healthcare and disease treatment. The Alliance for Regenerative Medicine (ARM) recently reported on the robust state of the industry and identified that revenue from cell therapy products grew from $460 million in 2010 to $1.3 billion in 2013. There are currently more than 40 commercially available cell therapy products with indications ranging from cardiovascular to cancer and non-healing wounds. The pipeline for these therapies is also expanding. ARM reports nearly 270 trials underway (Phase 1 through Phase 3). Another 58 projects are in the research stage and 245 in pre-clinical. Adding to this total, there are 77 industry-sponsored cell-based immunotherapy trials. Cell therapy represents a very different approach to treatment when compared to small molecules or many biologics. As such, regulatory authorities are evolving and adapting their approach to help ensure patient safety and efficacy of these innovative and complex therapeutics. A recent decision by regulatory authorities in Japan allows for an accelerated pathway for approval. This presents a tremendous opportunity for the industry, but at the same time, exerts tremendous pressure on developers to rapidly and efficiently characterize their products and processes in order to take advantage of such accelerated pathways. This article provides an overview of current regulations for cell-based therapies in the United States (US), European Union (EU), and Japan, and considerations for working successfully within these frameworks. It also describes a structured approach to process development that can help achieve accelerated timelines…
Tangential flow filtration (TFF) microfiltration has been used as one of the choices for clarification of mammalian cell or microbial cell culture in the biopharmaceutical industry. Unlike the ultrafiltration process for protein concentration and the diafiltration application where the feed solution is relatively clean (free of colloids or larger particles after the clarification/purification process), the microfiltration process needs to handle a rather high-fouling feed stream such as cells, cell debris, colloids, etc. In a previously published article, we discussed that a TFF microfiltration step is limited by a maximum throughput or capacity obtainable under a given set of operating conditions. Some distinct microfiltration characteristics, such as critical permeate flux, permeate flux control, and maximum throughput were explained in that article…
Kojic acid is produced industrially by the Aspergillus species using aerobic fermentation processes. Kojic acid has applications in several fields such as the pharmaceutical, food production, cosmetics and dermatology, agriculture, and chemical industries. The production of kojic acid is greatly increasing, based on the demands of these industries, and studies focused on improved processes are ongoing. This article will discuss the methods written about by various members of the scientific community…
The use of thrombolytic agent, streptokinase (SK), has been adapted to treat patients with the medical condition, hemorrhoids, in a new pharmaceutical formulation. Part of the development process included studies for measuring SK biological activity in the suppository product. Thus, the main objective in this study was in adapting and validating an established chromogenic substrate method for biological activity quantification of SK extracted from suppositories. By using several solutions and methods described in this paper, results revealed 103.82–124.99% of SK biological activity recovery and high molecular integrity. The chromogenic substrate method was specific for SK, and linear from 200– 600 IU mL-1 (R2 = 0.995 ± 0.002) with a variation coefficient of less than 7.11% and 12.62% for repeatability and reproducibility experiments, respectively. SK biological activity values estimated by the chromogenic substrate method were comparable with those estimated by the clot lysis method used as the reference. We have concluded that the method validated in this study was specific, accurate, and precise for quantifying biological activity of SK extracted from a suppository formulation intended to treat patients with acute hemorrhoids.
Dendritic cell (DC) population is a key functional constituent of cell-based immunotherapy drugs. The correct cell count and adequate viability of DCs are one of the quality control criteria for the final product release. The number of viable DCs is historically determined by microscopy using a manual counting method: Bürker chamber, and trypan blue dye for dead cell exclusion. The manual method can have significant variability between cell counts determined by different people performing the procedure, which may contribute to an unstable manufacturing process. The manual method is also timeconsuming for the operator. An automated cell counting process helps remove the variability between operators and can free up the operator for other tasks. The Vi-CELL® XR is an automated cell counting and viability analyzer that uses the trypan blue dye exclusion method. The Vi-CELL was evaluated as a suitable method for quality control of DC counts and viability for a dendritic cell-based biologic drug. The test for Vi-CELL counting accuracy was performed three times each on known concentration control beads, under the same operating conditions. The diameter and circularity of dendritic and lymphocyte cells was determined by a NIKON™ Eclipse microscope to set up the “correct recognition of DC. The size range for DC was established so that lymphocytes could be excluded. The number of total DC, viable and also non-viable, were analyzed and compared to Bürker chamber counting. There was no significant difference between the DC count obtained by Vi-CELL and by Bürker chamber. Vi-CELL automated cell counting was established as a method which is accurate and suitable for use with dendritic cells.
As a contract manufacturing organization (CMO) in this environment, it is essential for hameln pharma to deliver goods to their customers reliably, in terms of quantity, delivery time, and quality. Therefore, the topic of quality assurance plays a huge role— for both final packaged units as well as for bulk products. After a long-term analysis of the bulk product weighing process, hameln pharma’s objective was to significantly streamline the time-consuming process of manual counting and visual inspection. Moreover, taking cGMP standards into account, they wanted to optimize their existing process in order to remove any possibility of incomplete package volumes. Katrin Strasser, hameln pharma’s operational excellence expert, explained that: (1) packing box weights fluctuated with humidity levels during their manufacture; (2) labels for product packages varied; and (3) the actual number of items in a box carton were not always consistent
