One of the major concerns facing relatively young biotechnology companies once a lead product has been identified is the issue of manufacturing. Usually this involves the upscaling of a lab-scale process while at the same time, complying with good manufacturing practice (GMP) to ensure a reproducibly-produced and consistent product. It also involves the establishment of specific and robust assays in process controls and release criteria. This issue has become more acute in the EU since 2004 due to the EU Clinical Trials Directive requiring GMP-certified production of investigational medical products even for phase I trials. Startup biotech companies are often limited in their finances and resources, as well as being bound by tight milestones. Quite often the expertise in upscaling and GMP-compliant production as well as the facilities and equipment required are not available in-house…
BioProcessing Journal Posts
In recent years, cell therapy has been suggested as a promising approach for repair and regeneration of damaged tissues. VesCell™, a blood-derived autologous cell therapy product consisting of ex vivo enriched angiogenic cell precursors (ACPs) was developed by TheraVitae for the treatment of severe heart diseases. A non-mobilized, blood-derived cell population consisting of low density cells, termed synergetic cell population (SCP), was isolated and cultured in the presence of serum-free medium (X-Vivo 15, Lonza, Walkersville, MD, USA) supplemented with growth factors and autologous serum to yield VesCell. Significant cell numbers (>50×106) exhibiting morphological, immunocytochemical, and functional characteristics of the angiogenic cell lineage were obtained from blood samples. The ACPs expressed the hematopoietic stem cell (HSC) markers CD34, CD133 and CD117, as well as specific angiogenic markers such as vascular endothelial growth factor receptor 2 (VEGFR2) (receptor 2 [R2] is also known as kinase domain region [KDR]), CD144, and CD31…
The efficacy of pharmaceuticals, nutraceuticals, and cosmeceuticals depends not only on the chemical composition of the active ingredients, but also on the formulation of the product and the method of delivery. Nanoemulsions—formulations that encapsulate drug or nutrient molecules in sub-micron-sized oil droplets suspended in water—have been found to increase the rate and level of absorption into the body, and offer other benefits including the mitigation of side-effects as well as an antiviral and antibacterial action. With an emulsifier layer surrounding the droplet, nanoemulsions exhibit high levels of stability for extended periods of six months or more…
Controlled cell deposition by way of micrometer-sized jets are increasingly becoming a fiercely pursued area of research. We recently uncovered the ability to jet living cells using one such jetting methodology, now referred to as bio-electrosprays. This technique has never been explored for processing living cells until now. Electrosprays charge media within a needle, subsequently imposing an external electric field to assist in drawing the media into a micro-jet. The resulting instabilities assist in jet break-up, forming cell-bearing droplets. These droplets containing viable cells could be deposited onto a wide variety of biological and non-biological substrates. In this article, we report our developmental studies into this jet approach with a view to the successful handling and deposition of primary neonatal cardiac myocytes…
Key questions for any company planning to build a new facility include processes to be followed for effective design, commissioning, and qualification. Pilot plants need to be flexible, but as flexibility increases, so does complexity and cost. The scope of the new clinical trial pilot plant for bioprocess operations at Eli Lilly and Company (K360) was based on specific technology platforms and extensive benchmarking. Global regulatory issues had to be considered in the design as well because the material it produces will be used worldwide. The K360 plant has the capability to produce mammalian, bacterial, and yeast-based protein and peptide products following typical processes for growth in bioreactors. The protein or peptide of interest is recovered following fermentation and then purified in the facility. The plant’s output is bulk active pharmaceutical ingredient (API)…
Proteins are widely used in research, medicine and industry, but its extraction from their natural sources can be difficult, tedious and expensive. Therefore, a simple and inexpensive system that allows large-scale production of safe recombinant proteins will always be highly desirable. Traditional production systems that use microbial, insect and mammalian cell cultures have drawbacks, in terms of cost, scalability and product safety. Several studies have shown that molecular farming in plants has many practical, economic, and safety advantages as compared to these conventional methods. Thus, the use of plants for recombinant protein synthesis is gaining wide acceptance…
A variety of affinity chromatography mechanisms exist that exploit either immobilized proteins or small molecule ligands. Among them, protein-A chromatography is widely used as a platform technology for a commercial-scale manufacturing of therapeutic monoclonal antibodies. Antigen, dye and specific ligand-columns are used to purify target proteins for research uses and diagnostic applications. It uses specific interactions between affinity columns and target proteins. In general, the samples containing a protein of interest, such as cell culture media, serum, and tissue or cell lysates, are loaded on to the affinity columns; the proteins will normally bind to the column due to high affinity…
The search for new and more effective drugs is a complex and challenging endeavor requiring a number of strategies for identifying and processing new drug candidates. A common tool used in this search is high-throughput screening (HTS) of a large library of small molecular weight compounds. In each of our HTS campaigns, more than 500,000 compounds are tested for biological activity against one of our many molecular disease targets in order to identify compounds of potential therapeutic interest. High-throughput screens can be divided into two major types: those using cells, and those not using cells. At least 50% of our screens are cell-based and require a consistent, uniform supply of cells throughout the screening campaign. The provision of the cells is a primary consideration in our cell-based assays and therefore, an automated cell culture laboratory was included in our HTS facility. This laboratory serves two functions: the preparation of cell banks, and the daily provision of microtiter plates containing cells for the HTS…
Enriched or pure oxygen is increasingly being used to improve mammalian and microbial cell culture productivity. Sterilizing filtration of the process gas stream is required to remove all microbial contaminants. The filters used to sterilize the gas stream must meet demanding requirements. They must be capable of withstanding sterilization and integrity testing after each use. Oxygen challenges filters because filter components may suffer corrosion and filter materials can potentially ignite under extreme conditions. So the components of filters used with pure oxygen should be tested and rated for pure oxygen service. This article will delve into the main issues involved in sterilizing enriched or pure oxygen gas streams…
The “Lean” manufacturing process management methodology is derived largely from Toyota Motor Corporation’s automotive production system, implemented as a response to the problems they observed within their production facilities over 50 years ago. The principle of reducing costs by eliminating waste—also known as “Lean Thinking”—has been gaining momentum as a continuous improvement philosophy for all sorts of industries outside of its automotive industry origins. In recent years, we have seen several examples of successful Lean implementations in the pharmaceutical and biotech companies. Multinational corporations such as Merck, Pfizer, and GlaxoSmithKline have reported significant gains by applying Lean not only to manufacturing, but also in critical areas like quality control, regulatory adherence, and administration management…