Upstream Development

Fine-Tuning ADCs for Best-in-Class Therapeutics

Antibody–drug conjugates (ADCs) use the targeting ability of a monoclonal antibody (MAb) to deliver a highly biologically active drug to diseased cells while sparing healthy cells, creating potent and effective therapies. This emerging class of novel drugs currently focuses almost exclusively on cancer treatment. Two blockbuster ADCs — brentuximab vedotin (Adcetris from Seattle Genetics) for treatment of rare lymphomas and ado-trastuzumab emtansine (Kadcyla from Genentech/ Roche, manufactured by Lonza) for treatment of HER2-positive metastatic breast cancer — have improved treatment…

Automated Mini Bioreactor Technology for Microbial and Mammalian Cell Culture: Flexible Strategy to Optimize Early Process Development of Biologics and Vaccines

The use of mammalian and microbial cells in the production of biologics and vaccines is well established, and the majority of the top 10 drugs are now manufactured in this way. There is a significant and growing pipeline of new biologics (1), which in combination with increased pressure on cost reduction and generic competition from biosimilars (2), means that many biopharmaceutical companies are looking for ways to improve productivity in their development laboratories to ensure that upstream processes are efficient…

Design of Experiments with Small-Scale Bioreactor Systems: Efficient Bioprocess Development and Optimization

Design of experiments (DoE) is one of the most valuable techniques for organized and efficient planning, execution, and statistical evaluation of experiments. Although a DoE investigation can be completed using several runs in one bioreactor, small-scale bioreactor systems designed for parallel operation (such as the ambr15 or ambr250 systems) provide the optimal basis to economically realize a series of experiments. Because of the multitude of interdependent parameters involved in applications such as cell line development, culture media screening, and the…

Consistently Superior Cell Growth: Achieved with New Polyethylene Film Formulation

During the past decade, single-use bioprocessing bags and bioreactors have gained a significant foothold in the biopharmaceutical industry because they offer a number of advantages over traditional stainless steel equipment, especially for clinical production, multiproduct facilities, and emerging economies. At the same time, some companies are concerned that plastic materials might release potentially toxic substances that could affect cell growth and product titers (1). In a worst-case scenario, they could even compromise drug safety when a company uses disposable bags…

Verification of New Flexsafe STR Single-Use Bioreactor Bags: Using a CHO Fed-Batch Monoclonal Antibody Production Process at 1,000-L Scale

In the past decade, single-use bioreactors have gained wide acceptance for biomanufacturing. The biopharmaceutical industry is increasingly interested in performing modern production processes in single-use facilities. That trend is driven by the time and cost benefits of single-use technologies, as well as the enhanced manufacturing flexibility they offer (1). With single-use bioreactors increasingly used in late-phase clinical trials and commercial production, their quality, reliability, and assurance of supply becomes more critical. Many industry experts consider process control of film and…

Targeting G Protein–Coupled Receptors with Biologics for Therapeutic Use, Part 2

In part 1, we summarized the advances made in new approaches developed to address the challenges of antigen generation for targeting G protein–coupled receptors (GPCRs). We reviewed the antibody and biologics pipeline with progress highlighted by some interesting case studies on new targets (1). Here, we conclude by reviewing progress attained with other biologics. Peptides Targeting G Protein–Coupled Receptors More than 50 peptide-based therapeutic products are commercially available, but very few of them have been derived from recombinant display technology.…

Expansion of Human Mesenchymal Stem Cells: Using Microcarriers and Human Platelet Lysate

Cell therapy holds the promise of delivering the next generation of future medical breakthroughs. In this respect, multipotent progenitor cells such as human mesenchymal stem cells (hMSCs) have attracted high clinical interest because of their ability to differentiate into various cell types and their immunoregulatory properties. Furthermore, hMSCs express only low levels of class I major histocompatibility complex (MHC I) molecules on their surfaces and are therefore invisible to a host’s immune system. Finally, hMSCs can actively suppress the innate…

A Novel Solid-Media E. coli Platform: Comparison with Standard Fermentation Processes

MicroProtein Technologies Inc. has developed the MPTxpress high-yield, low‑cost, recombinant Escherichia coli manufacturing platform. Rather than using liquid culture media within stirred bioreactors, the system uses trays filled with semisolid (gelled) culture media overlaid with or without a permeable membrane on which the E. coli is cultured. Compared with conventional liquid fermentation platforms, the MPTxpress system reduces the number of steps in up- and downstream processing and required infrastructure, significantly improves yields, and lowers costs. It provides simplicity for mixing…

Due Diligence of Early Stage Technologies: Achieving Rapid Product Development with Low R&D Costs

Increased understanding of human diseases at molecular and cellular levels is leading to development of novel life-science technologies. Such advancements typically pertain to discovery and manufacturing of novel human therapeutics, new modes of drug delivery, and novel diagnostic technologies. The majority of those technologies are developed by early stage biopharmaceutical companies that have a greater appetite for risk than do larger companies. Early stage biopharmaceutical companies, however, have limited capital raised through personal sources, angel investors, venture capital, or government…

Targeting G Protein–Coupled Receptors with Biologics for Therapeutic Use, Part 1

G -protein coupled receptors (GPCRs) represent a target superfamily linked to many disorders across all therapeutic areas. Although this target class has been historically treated by small molecules and peptides, antibodies can offer a number of advantages over such molecules by virtue of their specificity, dosing frequency, and restricted penetration. They also can provide other functional effects specifically mediated by the Fc region (ADCC and CDC) as well as different modalities such as those offered by bispecific and antibody drug…