Martin Smith, PhD, has been with Pall for about nine years and assumed the role of chief technology officer at Pall about 18 months ago. He spoke with Cynthia Challener, PhD, about Pall’s biopharmaceutical business unit and how the company is positioning its technology suite for a continuous process paradigm. Smith: There is no doubt in our minds that we see movement toward continuous bioprocessing. When you look across an array of different industries, the move to continuous or parallel…
Although implementation of continuous manufacturing for biopharmaceuticals is in the early stages, continuous cell culture technology has been around for close to thirty years. Perfusion was initially developed in the late 1980s as a means for increasing protein titers (1). However, high costs driven by media consumption limited widespread commercial adoption. In the same time frame, advances in cell line engineering, media composition, and bioreactor design led to 10-fold increases in titers for batch and fed-batch modes, eliminating the first…
As an increasing number of cell therapies move into late-phase trials, developers are considering innovative solutions to address scale-up and commercialization challenges. Many of their questions focus on the technologies and engineering strategies that will be needed to optimize their processes, especially bioreactors. At the January 2016 Phacilitate Cell and Gene Therapy World conference, Siddharth Gupta, a scientist at Lonza (Walkersville, MD), talked about the effects of upstream process decisions on product quality in his presentation “Bioreactor Manufacturing Platforms: So…
Production of recombinant proteins usually happens in suspension cultures, with oxygen limitation playing a major role. Oxygen and nutrition feeds are of great significance to aerobic suspension cultures. Oxygen is often the controlling factor in orbital shaken systems because oxygen transfer occurs only through diffusion, which is limited by gas-exchange surface and mixing characteristics. Here, we compare growth characteristics of microbial cultures in a standard shaken incubator with those of cultures in a RAMbio fermentation system, paying particular attention to…
Product quality attributes are critical for the functionality and manufacturability of therapeutic antibodies. They can be significantly influenced by a number of production process parameters, such as cell culture media. The composition of growth and feed media can influence antibody glycosylation, including the concentration of ammonia, glutamine, glucose, and metal ions (1, 2). Thus, it is critical during media development and optimization to monitor and consider a culture medium’s impact on glycosylation. For therapeutic antibodies whose mechanism of action includes…
Follicle-stimulating hormone (FSH) is a heterodimeric glycoprotein consisting of noncovalently linked α and β subunits. It stimulates the growth of immature follicles in ovaries and primary spermatocytes in testes and thus plays an important role in human reproduction (1). Human menopausal gonadotropin for infertility treatment was first introduced into clinical practice in 1950 (2, 3). Subsequently, treatments with urinary FSH have been replaced by recombinant human FSH (rh-FSH), which has been shown to provide several advantages such as absence of…
Often simply referred to as capacitance, radio-frequency (RF) impedance has been used for over two decades to measure online biomass. It is generally regarded as the most robust and reliable method to monitor live-cell concentrations in mammalian cell culture (1). Many biopharmaceutical companies have now made the transition from conventional glass or stainless steel multiuse (MU) vessels to single-use (SU) bioreactors. Disposables are rapidly becoming the preferred platform for new processes requiring current good manufacturing practice (CGMP) compliance. At the…
Over the past decade, the application of chemical optical sensors for bioprocess monitoring has gradually taken roots. Constant further development of this measurement technology and the possibility to manufacture such sensors in various designs (even for single-use applications) have led to new state-of-the-art devices for the biotechnology sector. Chemical optical sensors enable in situ, real-time monitoring of important culture parameters without sampling and therefore without disturbing a culture. Implementing this technology can decrease workloads and deepen knowledge about bioprocesses. In…
In biopharmaceutical development and manufacturing processes, single-use technology has become widely accepted (1). Storage and cultivation bags are particularly common. They are fabricated from plastics consisting of multilayer films and are typically provided gamma-sterilized by suppliers (2). The bags offer several advantages such as savings in time and cost. Lowered contamination risk results from reduced cleaning and sterilization demands. However, some adverse effects of polymer films on cell growth and metabolism have been reported, both for storage and cultivation bags…
Biological additives such as yeast extracts and peptones are commonly used in growth-media formulations for biopharmaceutical manufacturing. In spite of drivers encouraging companies to reduce variability in mammalian cell culture processes by using chemically defined media, many microbial and mammalian processes continue to use biological additives in their growth-medium formulations and/or feeds. According to Sheffield Bioscience (Kerry, Inc.), at least six of the top 10 licensed mammalian-cell– derived biotherapeutic products are manufactured using biological additives (1). During process development, it…