March 2015

From the Editor – March 2015

In this month’s lineup, you’ll find a common theme of balancing operating costs against company cultures and corporate philosophies. This is far from new: You can’t responsibly run a business without making such calculations! But the value in taking a fresh look at them lies in how we are forced to dust off and reassess some assumptions (even prejudices). It is easy (and all too human) to persist with outmoded assumptions — and we cannot afford to do that given…

Spotlight – March 2015

Niche-Disease: Fanconi Anemia by Cheryl Scott Fanconi anemia (FA) is a rare, genetic blood disorder that causes bone-marrow failure. It prevents bone marrow from producing sufficient new blood cells and/or makes it produce faulty blood cells. Although FA is a blood disorder, it can affect many organs, tissues, and systems. Children who inherit the condition are at higher risk of being born with birth defects. It is a complex and chronic disorder that can be psychologically demanding. FA is not…

Modern Technology Transfer Strategies for Biopharmaceutical Companies

Application of industrial biotechnology has changed dramatically over the past decade. Stainless steel process equipment has largely given way to disposable systems, facilitating easier and quicker process configurations and up-scaling. Suppliers generally made incremental advances in the quality of raw materials and consumables to ensure that those could more readily comply, “off the shelf,” with regulatory expectations. Once out-of-reach analytical equipment such as mass spectrometers and cell analyzers are becoming more common place in development laboratories, which better enables biopharmaceutical…

Expanded Change Protocols: Benefits, Cost Considerations, and Regulatory Views

The US FDA Office of Biotechnology Products’ quality by design (QbD) pilot program defines an expanded change protocol (eCP) as a particular type of comparability protocol that will “describe the quality by design, risk- based approach linking attributes and processes to product performance safety, and efficacy” (1). Sponsors have explored a wide range of potential applications for eCPs (e.g., movement within or beyond an established design space, site transfers, and additional process modifications supported by either a QbD or traditional…

Special Report – 11th Annual BioProcess International European Summit

Now in its 11th year, the BioProcess International European Summit will host more than 400 bioprocessing professionals from adademia and industry. Five major streams, seven keynotes, poster presentations, and an exhibition hall will take place 14–15 April at the Swissôtel Düsseldorf Neuss in Germany. Together, these opportunities fulfill the conference’s mission: to be the event where the biopharmaceutical industry connects to share new ideas and innovations across all phases of bioprocess development. In two days, the BPI European Summit will…

Improved Fluorescent Labeling Efficiency of N-Linked, High-Mannose Oligosaccharides: Using 8-Aminopyrene-1,3,6-Trisulfonic Acid (APTS) for Analysis of Glycoproteins

Glycosylation of proteins, including monoclonal antibodies (MAbs), is recognized as important for the efficacy, immunogenicity, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) of biotherapeutics (1–6). So research and development of protein candidates is increasingly focused on the effects of glycosylation and how its pathway is affected in the Golgi system of cells involved in biosynthetic processes (7). Such attention on glycosylation has helped advance analytical technologies such as high-pH anion-exchange chromatography (HPAEC) (8); normal-phase chromatography (NP- HPLC), hydrophilic-interaction chromatography…

The Importance of the Concentration-Temperature-Viscosity Relationship for the Development of Biologics

JIM DELILLO (WWW.FREEIMAGES.COM) Patient preference and a competitive landscape in the parenteral market have fueled the need for convenient delivery systems and a desire for less‑frequent dosing injections. Monoclonal antibodies (MAbs) often have high dose requirements, so they must be formulated at very high concentrations (1). At low concentrations, an antibody solution’s viscosity increases moderately as a function of protein concentration. But at high concentrations (>100 mg/ mL, depending on the molecule), viscosity increases exponentially (2, 3). Thus, a specification…

Characterization of Postcapture Impurity Removal Across an Adsorptive Depth Filter

In the manufacture of monoclonal antibodies (MAbs), the first purification step following harvest clarification is normally protein A affinity chromatography because of its high selectivity for IgG and high process yield (1, 2). At this stage, a MAb is eluted from a protein A ligand at low pH and then held or adjusted to a low pH (pH ≤ 3.8) for a given amount of time before pH adjustment, usually ≥30 minutes, in a virus inactivation (VI) step targeted at…

A Multidisciplinary Approach to Manufacturing Biotherapeutics

Optimizing antibody manufacturing processes has gone beyond the first-order goal of achieving elevated protein titers and now also focuses on understanding biologic and manufacturing process variables that define cellular machinery and protein quality. A holistic approach to biotherapeutic manufacturing incorporates several applied disciplines such as biology, engineering, process control, signal processing, and modeling to reduce the “black-box” model of cell- based protein production into an operational design space. This is in line with the US Food and Drug Administration’s quality…

A Quick Guide for Sourcing Biopharmaceutical Raw Materials

Before the ratification of regulatory guidelines from The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q8–Q11 (1–4) — whose scope includes raw materials for biopharmaceutical production — many drug manufacturers chose the most cost-effective and readily available raw materials sourcing options without specifically considering the provenance of those materials. Depending on the chosen supply chain, such materials could be of widely varying quality and not necessarily suitable for a destined application. Raw-material…