Biochemicals/Raw Materials

Emerging Challenges to Protein A

Protein A affinity chromatography has been a target for replacement since its commercial debut, mainly because of its high acquisition cost. The technique became established despite the cost because it was born into an industrial culture that favored speed to market over manufacturing economy (1). Vendors have since strengthened protein A’s position with incremental but worthy improvements such as higher capacity, lower ligand leaching, and modest tolerance of NaOH. Collateral improvements in polishing technologies, such as the high throughput and…

Virus Risk Mitigation for Raw Materials

Recombinant protein–based medicinal products and modern cell-based vaccines have a very strong safety history with respect to viral and microbial contamination. However, virus contamination incidents do occur occasionally in manufacturing processes, and they can consume many resources and be expensive to rectify. The root cause of contamination incidents in recent years is most likely the use of contaminated raw materials. These include bovine serum contaminated with reovirus, epizootic hemorrhagic disease virus, Cache valley virus or vesivirus 2117; porcine trypsin contaminated…

Standards for Ancillary Materials Used in Cell- and Tissue-Based Therapies

Cell- and tissue-based therapies are being used increasingly to treat many diseases for which currently no other adequate treatment options are available. These products contain human or animal cells that can replace, regenerate, or augment a recipient’s diseased, dysfunctional, or injured cells, tissues, or organs. Cells or tissues might be unmanipulated, or their biological characteristics can be altered ex vivo before administration of the final product to patients. Examples of cell therapies range from traditional blood transfusions to recent approaches…

Upstream Chemistry Analysis in Cell-Based Process Development

Cell line selection is important to any pharmaceutical company’s development pathway for biological compounds (1). In cell-line selection laboratories, many different, slightly variable cell lines are tested in parallel for desired characteristics. Candidate cell lines are chosen for further development on the basis of their performance in basic tests of critical quality attributes (CQAs). Historically, such cell lines were selected in large-volume containers because it was necessary to have sufficient volume in culture to allow repeated sampling without damaging the…

Enhanced 2-D Electrophoresis and Western Blotting Workflow for Reliable Evaluations of Anti-HCP Antibodies

Biologic drugs are subject to unique regulatory and technical requirements because of their origin and expression in genetically engineered host cells, as well as their underlying physicochemical properties and elaborate purification processes. One such requirement is the accurate monitoring and effective removal of process-derived impurities such as host-cell proteins (HCPs) and DNA/RNA, viruses, cell culture media, chromatographic leachates, and so on (1). Of those impurities, HCPs are perhaps the most challenging to accurately monitor. Each expression system’s proteome consists of…

Protein A

The number of blockbuster monoclonal antibody (MAb) drugs continues to grow. In 2008, MAbs generated revenues in excess of US$15 billion (1), making them the highest-earning category of all biotherapeutics. The world MAb market will reach $62.3 billion in 2015, with next-generation therapeutic antibody revenues reaching $2.3 billion in 2015 according to Visiongain reports published in September and November 2011 (2, 3). Biosimilar antibodies will also begin to enter established markets as regulatory authorities clear approval pathways for them. Most…

A Salt-Tolerant Anion-Exchange Chromatography Sorbent for Flexible Process Development

In most downstream purification processes designed for biopharmaceutical drug production, dilution and diafiltration sequences are unavoidable. Such operations are routinely used to adjust a feedstock or chromatographic fraction to the optimal conditions required for best process performances. Nevertheless, those steps are often time, water, and labor consuming without participating directly in final product purification. Because biopharmaceutical production is increasingly driven by cost reduction, a possible means for enhancing process economics is to streamline purification by eliminating these unit operations before…

The Influence of Polymer Processing on Extractables and Leachables

Polymers provide a unique set of material properties, including toughness, chemical resistance, versatility, and low cost for both multiple-use and single-use bioprocessing systems. Polymer materials are manufactured as fittings and tubing for research and development (R&D) laboratories, as containers for bulk chemical and biological storage, as filters and separation technologies for downstream processing, and as containers and bottles for drug substance storage. These components and systems are helping drug companies improve their manufacturing flexibility, reduce their operating costs and capital…

Development and Qualification of a Scalable, Disposable Bioreactor for GMP-Compliant Cell Culture

During the past decade, single-use bioreactors have become widely accepted for use in cell culture process development and clinical manufacturing. Their key benefits over stainless steel bioreactors are flexibility, cost, and time savings associated with the reduction of cross-contamination risks (1). Here, we describe our approach to development and qualification of the Biostat STR single-use, stirred-tank bioreactor. Unlike other stirred single-use bioreactors, it offers a similar design to that of well-established, conventional (stainless steel) stirred-tank bioreactors. Disposability of the single-use…

PEGylation of Biologics

In the 1970s, life-science researchers envisioned protein therapeutics as the ultimate targeted therapy. Companies could use them to address genetic deficiencies and cancer, among other disease classes, as well as to nudge the immune system for treating autoimmune disorders. The first therapeutic proteins were derived from animal or microbial cells, so patients launched immune responses to them that could curtail their activity and produce dangerous side effects. PEGylation was initially used to prevent immune responses with such drugs. PEG is…