Monoclonal antibodies and recombinant proteins have increased in importance and gained success as therapeutic agents in treating various diseases. Biomanufacturing of such a biopharmaceutical product by cell culture follows a main route. Upstream processing is strictly biology-driven, while on the other hand, purification is engineering driven. Fermentation is setting the pace. To some extent, that pace is a result of recent advances in cell culture, greatly increasing the densities of cells along with cell-related contaminants…
Category: <span>Manufacturing</span>
Manufacturers of biological products have come to accept that it makes sense, from both a business as well as a regulatory perspective, to address GMP compliance issues with bioprocessing methods as early as possible in product development. Logically, this same reasoning would also apply to the associated analytical methods used to characterize the product; however, companies still frequently leave methods optimization and validation until later in the developmental timeline which can expose them to unexpected regulatory challenges. In addition, as therapeutics increase in complexity (e.g., cell therapies, transgenics), it raises the likelihood that product characterization will be assessed by novel and increasingly intricate assays—making it difficult to follow a “one size fits all” approach to method selection, development and validation…
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…
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…
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)…
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…
In today’s biopharmaceutical pipeline, monoclonal antibodies are a predominant modality for a broad range of clinical indications, including inflammatory disorders, oncology, and infectious diseases. More than two dozen antibody-based products are commercially available. In 2004, six of the 12 new biopharmaceutics that gained approval in the United States and Europe were antibody-based products. Most antibody therapies require high doses over a long period of time, which requires large amounts of purified product per patient. Therefore, manufacturing capacity to meet the demands of antibody production is a real challenge. It is desirable to have highly productive and consistent manufacturing processes. In addition, speed to market is critical to deliver health benefits to patients quickly and to achieve business success…
In the last few years, we have seen many biotech products approved by FDA. These products have gained public awareness because of their ability to treat several debilitating diseases with very minimal side effects, and thereby impact the quality of life for many people. As a result, the biotech industry is constantly in the news for its successes and programs to develop new therapeutics for many unmet medical needs. Immunomedics, Inc., a New Jersey biotechnology company, recently completed an expansion project that included new bioreactor manufacturing suites and support laboratories. Building on the company’s existing headquarters site and fully integrating the new capacity into the existing operational facility, the project spanned two years and was completed in 2003…