Analytical

Analytics for Modern Bioprocess Development

Twelve years ago, about the same time the US Food and Drug Administration was putting the finishing touches on its quality by design (QbD) and process analytical technology (PAT) guidelines, I wrote an article about breakthrough pharmaceutical educational programs. That article included the perspectives from a few members in academia of the future essential skills for pharmaceutical students. At the time, bioinformatics and computerized industrial process modeling were relatively new disciplines, but their importance in future manufacturing was clear. Several…

Essentials in Quality By Design

Quality by design (QbD) is a systematic approach to drug development. It begins with predefined objectives and emphasizes product and process understanding and process control, all based on sound science, data-based decision making, and quality risk management (QRM). As introduced by the US Food and Drug Administration (FDA), QbD brings modern drug development methodologies to chemistry, manufacturing, and control (CMC) teams working on biologics, pharmaceuticals, and vaccines. The innovations associated with QbD are not so much the development concepts (which…

Reference Standards for Therapeutic Proteins: Current Regulatory and Scientific Best Practices

Sponsors developing and manufacturing protein therapeutic products use a variety of analytical tests (e.g., cell-based potency and chromatographic assays) to assess quality attributes of their active ingredients and drug products. Those tests are used to assess product quality in a number of activities, including characterization, comparability, lot release, and confirmation product quality and stability. Reference standards play a critical role in calibrating and confirming the suitability of such tests and in helping analysts to draw scientifically sound conclusions from data…

Cell Therapy Bioprocessing Technologies and Indicators of Technological Convergence

The cell therapy industry is undergoing a natural evolution from scientific curiosity into a commercially and clinically attractive opportunity (1). This evolution is by no means complete, and growing evidence suggests that its progression is driving significant developments in cell therapy bioprocessing — notably, convergence. Table 1:&#8 194; () Progressively, bioprocessing technologies primarily used in production of noncell-based products are being evaluated for cell therapy bioprocessing applications (2). Consequently, this process of convergence is leading to an increasing proportion of…

Activatable Immunoconjugates for Target Cancer-Cell–Specific Diagnosis and Therapy

In cancer treatment, early diagnosis and targeted therapies are assumed to yield the highest cure rates. However, most current methods are limited by their low sensitivity to early disease and a lack of specificity for targeted cell killing. Newly developed, activatable immunoconjugates assist in the accurate detection of cancer through in vivo imaging with high target-to-background contrast (1,2). They also provide for the possibility of highly specific, light-mediated treatment with minimal effects on healthy cells surrounding tumors (3). In fact,…

Cell Therapy Manufacturing

Fueled by a recent resurgence in public financing and compelling clinical data for indications as diverse as acute macular degeneration and pancreatic cancer, a growing number of cell therapies are driving toward pivotal clinical studies and commercialization. Although regulatory precedents have been set for various autologous and allogeneic products in the United States, Asia, and the European Union, regulatory guidance continues to evolve for a widening array of cell products. Adult stem cells (e.g., mesenchymal stem cells), embryonic stem cells,…

Accelerating Purification Process Development of an Early Phase MAb with High-Throughput Automation

    Monoclonal antibodies (MAbs) are the fastest growing segment in the biopharmaceutical industry because they are potentially efficacious in the treatment of diseases such as cancer and autoimmune disorders (1,2). With steadily increasing demand for efficient and affordable therapies, speed to clinic/market is important, and biopharmaceutical companies push multiple drugs into development each year to ensure business sustainability (3,4,5,6). Downstream purification process development for therapeutic MAbs is a critical step on their path to reach clinical trials and beyond…

Single-Use Bioreactors and Microcarriers

Cell-based therapies hold promise for treating many acute and chronic diseases (1). Optimism surrounding that therapeutic potential has driven the initiation of multiple clinical trials in pursuit of such treatments. Procedures for preparing these therapeutic agents begin with selective isolation of cells from desired tissues. That is followed by ex vivo expansion of cells of desired phenotype and functionality. Once expanded to acceptable levels, cells are stored to preserve their viability during transportation to treatment facilities. The final step in…

Assessing Flange Strength and Dimensional Variability

Plastic syringes are viable alternatives to glass syringes in the biopharmaceutical market. They have two main advantages over glass syringes: their break resistance (specifically on the finger flange) and their ability to maintain tighter dimensional tolerances and less variability (because of the flexible molding process). Both attributes are critical when a 1-mL long prefilled syringe is used with an autoinjector device. The high break resistance of plastic syringes can reduce the number of rejected units during a fill–finish process. And…

Nucleic Acid Impurity Reduction in Viral Vaccine Manufacturing

Commercial-scale viral vaccine manufacturing requires production of large quantities of virus as an antigenic source. To deliver those quantities, a number of systems are used for viral replication based on mammalian, avian, or insect cells. To overcome the inherent limitations in production outputs with serial propagation of cells, mammalian cells can be immortalized, which increases the number of times they can divide in culture. Modifications that immortalize cells are typically accomplished through mechanisms similar to those converting normal cells to…