Single-step harvesting of a high-density cell culture from a Biostat STR bioreactor with Sartoclear Dynamics body-feed filtration from Sartorius Stedim Biotech (WWW.SARTORIUS.COM)

Downstream Disposables: The Latest Single-Use Solutions for Downstream Processing

Downstream processing has been considered a “bottleneck” in the manufacture of protein biotherapeutics ever since cell culture engineers began dramatically improving production efficiencies around the turn of the century. And as single-use technologies have grown in importance and acceptance, offering more solutions every year, their biggest challenges too have been in the separation, purification, and processing that follows product expression in cell culture. Many of the technologies familiar to process engineers — e.g., centrifugation and chromatography — present technical and…


Multicolumn Chromatography: Facilitating the Commercialization of Monoclonal Antibodies

Since 2001, global contract development and manufacturing organization (CDMO) CMC Biologics has completed more than 120 projects with at least 100 pharmaceutical partners. During that time, the company has taken a holistic approach to helping clients balance manufacturing risks and rewards. The team focuses on evaluating key technologies to deploy a constantly evolving set of capabilities in support of biopharmaceutical clients throughout their product lifecycles. Part of that commitment is continually evaluating what would best benefit customers and where key…

Figure 1: Right-sizing and rapid multicycling enables small-footprint downstream processing to match high-productivity upstream production (adapted from reference 1).

Membrane Adsorbers, Columns: Single-Use Alternatives to Resin Chromatography

Filtration membranes are used extensively throughout the biopharmaceutical industry for a range of applications, from coarse filtration to nanofiltration. Advantages of filter technologies include easy scaling, disposability, and (for many membrane filters) rapid and robust performance in a single-pass. The same advantages have been realized with membrane adsorbers. Chromatography resins are inherently disadvantaged by diffusion limits of the pores in chromatography media. Therefore, resin columns must be significantly oversized to match the performance of high productivity bioreactors. By comparison, membrane…

Microsoft Word - Goodwin - Repligen Manuscript 01Sep16.docx

Reducing Clinical-Phase Manufacturing Costs: Collaborating for Savings without Compromising Quality or Performance

In downstream purification of monoclonal antibodies (MAbs), the single greatest contributor to manufacturing costs is the expensive capture step typically based on protein A affinity chromatography. Almost since its introduction to bioprocessing, efforts have been made to reduce the cost of this step. Several alternative ligands have been promulgated as potential replacements for protein A, but they have proven difficult to adopt and scale up. Supplier companies have pushed for increases in capacity and economics, but those are always accompanied…


Special Report: A Strategy for Cost-Effective Capture Using Agarose-Based Protein A Resins

It is well recognized that the cost of Protein A resins is substantial. If a developmental monoclonal antibody (MAb) makes it to marketing approval and manufacturing, the high cost of purification using a Protein A resin is amortized over a large number of purification cycles, and the contribution to cost of goods is reduced to acceptable levels. However, a high percentage of clinical projects will fail, and the Protein A resin will be used only for a small number of…

Figure 1: Affinity chromatography principle: target-specific ligands are chemically immobilized or “coupled” to a solid chromatographic support. The complex mixture that contains the target molecule with impurities is loaded over the affinity column, and the target molecule that has specific binding affinity to the ligands on the resin will bind. Impurities are washed away, and the bound molecule is eluted from the column, resulting in its purification from the original feedstock.

Innovative Downstream Purification Solutions for Viral Vectors: Enabling Platform Approaches to Advance Gene Therapies

Over the past decade, gene therapy applications and their importance in the biopharmaceutical industry have been increasing. Gene therapies promise versatile treatment options that could revolutionize and transform medicine. As treatment modalities, they offer the possibility of long-term and potentially curative benefits to patients with genetic or acquired diseases. Gene therapies are designed to treat disease by delivering genetic material that encodes a protein with a therapeutic effect into a patient’s cells. It can be used to replace a missing…

Along with increased selectivity, mixed-mode and multimode media offer  significant potential operational cost savings by eliminating intermediate purification  steps that require additional time, materials, equipment, and personnel.

Selective and Flexible Chromatography Media: Improving Biopharmaceutical Operational Efficiencies

Continuing development in protein and peptide engineering have produced a broad range of new biological products with improved therapeutic and diagnostic potential. In the development pipeline, more than 900 biologic products target more than 100 diseases (1). Increased manufacturing complexities caused by closely related impurities and requirements to improve process efficiencies and reduce operating costs highlight the need for new approaches in protein purification. Platform-based chromatographic approaches have been successfully applied in separating and purifying monoclonal antibody (MAb) products. But…

Martin Smith, PhD, Chief Technology Officer, Pall Corporation

Preparing for Continuous Bioprocessing: An Interview with Pall Corporation’s Chief Technology Officer Martin Smith

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…

Figure 1:  Principles of simulated moving bed technology

Continuous Chromatography Is Now Possible for Clinical Manufacturing

Intensified and integrated bioprocess technologies are creating a paradigm shift toward more efficient, higher flexibility facilities for biopharmaceutical manufacturing. Continuous technologies that are designed as single-use systems help to greatly facilitate process intensification, delivering further efficiencies with reduced set-up times and elimination of the need for cleaning and cleaning validation. Chromatography is often considered to be a challenging bioprocess step, which has caused great interest in a simplified, safer solution. Continuous multicolumn chromatography using a single-use flow path is an…

Figure 1: The aminobenzoic acid ligand of
the CMM HyperCel mixed-mode cation
exchanger provides cation-exchange
functionality through the carboxyl group and
hydrophobicity-based binding through the
aromatic ring.

Optimizing Continuous Monoclonal Antibody Polishing By Using Coupled Unit Operations

The biopharmaceutical industry is under a great deal of pressure to modernize manufacturing to meet the challenges of production at vastly different scales for niche drugs as well as for expected massive blockbusters, biosimilars, and regional manufacturing. To address these challenges, the biopharmaceutical industry is embracing process intensification through single-use and continuous processing technologies. Implementing these technologies offers increased productivity and manufacturing flexibility and reduces the footprint, capital outlay, and operating costs. Pall Life Sciences has developed several technologies designed…