Upstream Development

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…

Process Challenges of Antibody–Drug Conjugates

With two products now on the market, and a host of others in clinical trials, antibody-drug conjugates (ADCs) are slowly becoming a big business. Designed to deliver extremely active cytotoxic drugs that are otherwise undosable, they take advantage of the targeting ability of a specifically designed monoclonal antibody (MAb) to “shield” a highly potent API (HPAPI) as it travels through a patient’s bloodstream after administration. Once the antibody reaches its target on the cancer cell, it will release the payload,…

Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell-Derived Products, Part 2 — Application

Here we apply our approach to validation of animal cell culture process changes using qualified, scale-down bioreactors. As described in Part 1 (including Table 1, Figures 1 and 2, and References 1–23), the goal is to facilitate implementation for the benefit of both the patients and industry. “Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell–Derived Products, Part 1 — Concept” appears on pages 38–45 of BioProcess International’s May 2014 issue. Process changes often entail validation,…

Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell-Derived Products, Part 1 — Concept

Implementing continuous process improvements is increasing in priority for the biopharmaceutical industry. Such implementation can be driven by product safety, purity, and stability enhancement opportunities as well as by cost-reduction pressures. Companies invest in projects to improve product quality assurance, safety, and yield as well as production efficiency (1). Such changes may come at any process stage, from early cell-growth methods through final-product packaging improvements. Examples include growth medium optimization, purification column operation optimization, and enhanced recovery during final filling…

Activatable Immunoconjugates for Target Cancer-Cell–Specific Diagnosis and Therapy

In cancer treatment, early diagnosis and targeted therapies are assumed to yield the highest cure rates. However, most current methods are limited by their low sensitivity to early disease and a lack of specificity for targeted cell killing. Newly developed, activatable immunoconjugates assist in the accurate detection of cancer through in vivo imaging with high target-to-background contrast (1,2). They also provide for the possibility of highly specific, light-mediated treatment with minimal effects on healthy cells surrounding tumors (3). In fact,…

Accelerating Purification Process Development of an Early Phase MAb with High-Throughput Automation

    Monoclonal antibodies (MAbs) are the fastest growing segment in the biopharmaceutical industry because they are potentially efficacious in the treatment of diseases such as cancer and autoimmune disorders (1,2). With steadily increasing demand for efficient and affordable therapies, speed to clinic/market is important, and biopharmaceutical companies push multiple drugs into development each year to ensure business sustainability (3,4,5,6). Downstream purification process development for therapeutic MAbs is a critical step on their path to reach clinical trials and beyond…

Single-Use Bioreactors and Microcarriers

Cell-based therapies hold promise for treating many acute and chronic diseases (1). Optimism surrounding that therapeutic potential has driven the initiation of multiple clinical trials in pursuit of such treatments. Procedures for preparing these therapeutic agents begin with selective isolation of cells from desired tissues. That is followed by ex vivo expansion of cells of desired phenotype and functionality. Once expanded to acceptable levels, cells are stored to preserve their viability during transportation to treatment facilities. The final step in…

Enabling Technologies

Many technological advancements in recent years have enabled companies to shorten time to market, to better understand their manufacturing processes, and to characterize their products well. In BPI’s December 2013 issue (pages 47–50), I reported on the first half of an informal reader survey about those technologies, with commentary from some survey participants and others. This month concludes with my examination of analytical, formulation/fill–finish, and facilities technologies. Analytical Technologies After writing several installments of our new “BPI Lab” series this…