BioProcessing Journal Posts

Regulations and common sense require that a manufacturer qualify both the raw materials and the suppliers the firm will use to produce GMP supplies of a pharmaceutical or biopharmaceutical. Because the firm is accepting legal liability for the quality of all raw materials, it makes good business sense to devote resources to these activities. This article explores how to assure that qualification is complete, efficient, and compliant with current good manufacturing practice (cGMP), and discusses the challenges faced by today’s manufacturers…

Manufacturing Risk Analysis and Management

Across many areas of biopharmaceutical development, the goal of consistently transfecting appropriate quantities of DNA into cells has often been a significant bottleneck. Electroporation — a method of temporarily permeabilizing cell membranes by using a short electric pulse — has gained ground in recent years as an effective means of transfection. A cell loading system based on electroporation has been designed for ex vivo cell modification in a clinical setting and for incorporation into cGMP processing applicat

Biologics Production

Proteins and their promise for revolutionizing drug discovery have come virtually full circle in just a few decades. The advent of genetic engineering and the emergence of early recombinant proteins such as insulin and interferon dramatically boosted the perceived value of proteins in pharmaceutical research and of protein drugs in particular. Although the lights dimmed somewhat on the promise of therapeutic proteins in subsequent years, more recent times have seen a resurgence of interest in proteins, particularly monoclonal antibodies. Perhaps most telling has been the dawn of the post-genomic era, which has cast a bright spotlight on proteins, long respected as the work-horses of the cell, for their usefulness in exploring cell function, unraveling biochemical pathways, understanding disease, and for their massive value as novel drug targets…

Biologics Production

Several developing countries, including India and China, have young biopharmaceutical industries that have based much of their growth potential on the production of what are currently known as “biogeneric” products, or “bioequivalent” versions of biologics that have already been licensed in Western countries. With a disdain for foreign patents, an established philosophy of copying Western innovations, and success in generic pharmaceutical manufacturing, this approach appeared to be the logical way to build a biologic manufacturing industry. However, there are numerous problems with this development strategy. First and foremost is the inherent incompatability of the very concepts associated with biogeneric products…

Biologics Production Manufacturing

From an intellectual property (IP) standpoint, probably the two biggest problems I encounter in my practice for early-to-middle stage technology companies are: (1) their failure to fully understand and keep abreast of the competitive intellectual property environment , and (2) their failure to institute procedures that will permit and encourage development of a strategic intellectual property portfolio. By “strategic,” I mean an intellectual property portfolio that focuses on both an offensive and defensive position — a portfolio that not only covers the product and all aspects of its manufacture, production, and applications (defensive portfolio development), but also provides significant blocking positions with respect to competitors’ efforts…

Risk Analysis and Management

The Good Manufacturing Practices (GMPs) are becoming more and more familiar in biotechnology, and concepts such as quality assurance or validation are now part of the background of clinicians and researchers involved in clinical trials. A recent European Community directive (2001/20/CE) states that GMPs should also be applied to investigational medicinal products and not only to products on the market. Vector supernatant is a so-called Active Pharmaceutical Ingredient (API) and is subject to the same guidelines as traditional drugs produced by the pharmaceutical industry. This has a deep impact in the field of gene therapy because clinical trials are often run by small biotech companies or, at least in the first phases, by academic centers. The field is continuously developing and, according to the progress of the clinical studies, new processes are necessary to produce large-scale amounts of vector supernatant in a safe and reproducible way…

Manufacturing Viral Vectors

Gene therapy is a promising medical technology that has the ability to treat inherited diseases. However, efficient and economical large-scale production of vectors is necessary to meet the potential patient demand. Several approaches have been evaluated for the mass production of retroviral vectors, including fixed-bed bioreactors, suspension cultures, and microcarrier cultures. In this article, we report on the use of a Cytopilot fluidized-bed bioreactor for the production of retroviral vectors from the human packaging cell line TEFLYRD…

Cell & Gene Therapy Viral Vectors

Currently, the U.S. Food and Drug Administration (FDA) recommends DNA sequencing for the structural characterization of gene transfer viral vectors in investigational New Drug Applications (INDs). While FDA provides guidelines on what should be sequenced in regard to these vectors, it provides little insight — beyond GLP/GMP (GxP) guidelines — into how the finalized sequence data should be obtained. There is presently no provision for determining which sequencing methodology (or methodologies) is most appropriate for obtaining a completed sequence characterization for each of the different vector classes, and there is no standard that outlines what DNA sequencing-specific criteria the data and data collection processes should meet in order to guarantee that the sequence is 99.99% accurate…

Nucleic Acids Research Uncategorized Viral Vectors

A growing number of separations’ scientists and process developers are looking beyond protein A sorbents for capture and initial purification of monoclonal antibodies. A variety of strategic and operational goals have prompted examination of alternative immunoglobulin-selective sorbents. Most broadly, many workers wish to eliminate design considerations associated with leached protein A. Also cited is a preference for sorbents that can withstand stringent cleanup using 1 M sodium hydroxide. In some applications, it is desirable to avoid the low-pH elution conditions typically employed with protein A sorbents — conditions that can foster aggregate formation. In still other cases, the target antibody may bind poorly to protein A. Finally, there may be interest in evaluation of immunoglobulin-selective sorbents less costly than protein A sorbents…

Biologics Production

The United States Pharmacopeia (USP) is a 184-year-old organization that has been in the forefront of technology since its inception. From publishing a manual about how to prepare therapeutic potions, USP has evolved into a compendium of standards and information on manufactured pharmaceutical products, with more than 4,000 monographs covering drug substances and biologics, and their dosage forms, excipients, and nutritional supplements. It is not surprising that the USP initiative in cell and gene therapy and tissue engineering has closely followed the emergence of these technologies…

Cell & Gene Therapy Regulatory Risk Analysis and Management