I have compiled a list of our most popular 25 blogs, podcasts, and webinars  for 2017 listed in alphabetical order.

Achieve Integrated and Scalable Continuous Chromatography

Over the last decade, advances in the upstream processing of monoclonal antibodies (mAbs) has resulted in higher bioreactor titers. With increasing titers, the production bottleneck has shifted to downstream processing. Hence, the biopharmaceutical industry has reached a milestone where the need for higher throughput in downstream processing is leading to the adoption of more efficient multi-column continuous (MCC) counter-current chromatography systems which increase overall productivity while significantly reducing consumables costs…

Addressing Buffer Bottlenecks using automated In-line conditioning and ready-made stock solutions for mAb processes

Multiple buffers in a wide range of formulations are required to produce a single biopharmaceutical. Because of the large volumes required, buffer preparation can easily become a bottleneck in production. Traditionally, buffers are prepared manually in the volume needed according to specific recipes. Due to the large quantities used, buffer management requires careful planning and considerable floor space is required for the preparation and storage of such large buffer quantities. In addition to high labor and facility space cost, there is a risk of human error and variability associated with such a time-intensive manual activity. Buffer variability can affect both quantity and quality of the final product…

Affordable Biologic Downstream Purification with Single-Use Protein A Membrane

At this year’s Boston Biotech Week there were many exciting talks on downstream purification and associated new technologies. In particular, there were several talks about optimizing the downstream purification process. One very interesting talk, given by Renaud Jacquemart, PhD Principal Scientist, Director Vaccines Process Sciences, was titled “Enabling Manufacturing Of Affordable Biologics Through The Use Of A Protein A Membrane
 In A Single-Use Purification Strategy ” and focused on the application of a fully single-use chromatography purification process in place of resins. This strategy envisions the use of a unique Protein A membrane for which Natrix recently signed collaboration agreements with Merck & Co. and Sanofi…

Antibody Fragment Purification Platform

Since the 1980’s monoclonal antibodies have revolutionized medicine and become a vital tool in fighting many diseases. While there are many new monoclonal antibodies in the clinical trial pipeline, there are also some innovative drugs made from just an antibody fragment. Due to the multi-domain structure of antibodies, it is possible to create smaller antibody fragments that still include the antigen-binding domain. Antibody fragments have some advantages over full-length antibodies and several antibody fragment-based biotherapeutics are in clinical research. Several antibody fragments have been approved and are commercially available, including: ReoPro®, Lucentis®, and Cimzia®…

Automated Adenovirus Purity Analysis Speeds Viral-based Gene Therapy Process Development

Adenovirus-based vectors are commonly-used gene delivery vehicles, especially in gene therapy applications where their efficient nuclear entry mechanism and low pathogenicity for humans are much-valued attributes. In addition, Adenovirus vectors can be produced in high titers and the particles are stable yet easy to modify. Several methods of manufacturing Adenovirus-based products are in use today, including small-scale production in cell culture flasks, suspension-based scalable platforms and large-scale batch manufacturing in fixed-bed bioreactors. Downstream purification steps include chromatography and filtration, the objective of which is to produce high-quality, high-purity Adenovirus particles in a scalable manner. Methods for analyzing the purity and integrity of the Adenovirus particles in a time and cost-efficient way are therefore critical for this task…

Automated, single-use filtration to increase efficiency in upstream and downstream operations

In examining ways to improve overall bioprocess efficiency, filtration is a step that can sometimes be overlooked. However it is a key area to improve efficiency, as it is part of both upstream and downstream operations and consumes sizeable resources. The application of single-use technologies coupled with increased automation have successfully improved efficiency in other bioprocess operations, thus it is logical that filtration would also benefit from these technologies…

Bioburden Contamination in Downstream Bioprocesses – Potential entry points for contamination and innovative solutions

Bioburden contamination in biopharmaceutical manufacturing is a big concern. Contamination carries both tremendous cost and preventing it requires strict control of several possible entry points. The cost of bioburden contamination for a company can involve lost time, lost material, batch loss, possible facility closure and extensive QA/QC time to ensure proper cleaning and validation. In the worst case scenario, it can prevent supply of much needed medicine to patients and loss of commercial revenue…

Continuous bioprocessing – moving from theory to reality

Continuous manufacturing has been established in several processing industries for many years, providing many benefits over batch manufacturing. The feasibility of continuous processing has now been shown for monoclonal antibodies (mAb) at both the process development (PD) and the production scales by early adopters…

Cost and impact of a bioburden incident

A major area for safety improvement is bioburden management. High up on any list of critical quality attributes (CQAs) for mAbs, you will likely find a requirement for the absence of microbial contamination. Apart from the potentially tragic impact on patients, the economic consequences of a batch failure are enormous. For the mAb blockbusters, a month production stop can result in lost revenues of up to USD 1 billion…

Direct vs. indirect methods for characterization and analysis of subvisible particles – A comparative study

Characterization and analysis of subvisible particles of biological origin can be challenging or give insufficient information. In this study Adeno associated virus (AAV) particles contaminated by host cell proteasomes are analysed with direct versus indirect methods performed in a standard laboratory setting to reveal the difference in performance and quality of the information obtained. The focus is on the ability to detect the AAV particles of interest and distinguish them from the contaminating proteasomes. The compact, tabletop MiniTEM system enables automatic sample screening and imaging together with direct measurements of particle size and particle classification. This method is compared with the indirect methods Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) measurements using Zetasizer Nano and NanoSight NS300 respectively. Both the DLS and NTA methods measure the Brownian motion of the particles or molecules in suspension and use the Stokes-Einstein equation to give the particle size distribution…

Downstream Bioprocessing Cost Modeling – Looking at Integrated Continuous, Single-use and Stainless Steel Platforms

Process economics are frequently discussed with respect to continuous biomanufacturing implementation. More specifically, are the potential cost benefits worth making a manufacturing change and in which situations are the benefits greatest? At Biotech Week Boston in September, there was a very interesting talk titled “Cost modeling of the downstream bioprocessing design space,” presented by Mark Schofield, Ph.D., Senior R&D Manager, Pall Life Sciences. In the talk, Dr. Schofield shows data related to cost modeling the downstream bioprocess design space. He also describes some of the challenges facing biomanufacturing including cost pressure, competition, and the rise of biosimilars, and how implementing integrated continuous operations can address several of these challenges…

Enabling Antibody-drug conjugate manufacturing using single-use systems in downstream – Extractables study demonstrates a good fit

Antibody drug conjugates offer tremendous therapeutic potential and the market for ADCs is expected to expand rapidly. However, antibody-drug conjugate manufacturing presents both technological and logistical challenges. Antibody drug conjugates are composed of three parts: an antibody specific for the tumor associated antigen, which has restricted expression on normal cells, a cytotoxic agent designed to kill target cells when internalized and released and, a chemical linker to attach the cytotoxic agent to the antibody. New linker systems are designed to be stable in circulation and release the cytotoxic agent after being internalized by the targeted cells. Because the cytotoxic agent is delivered in such small quantity, it must be powerful enough to kill the tumor cells. Therefore, the potency of these cytotoxic agents is 100-1000 fold more potent than cytotoxic agents delivered as free drugs…

Fine Tuning Viral Clearance Approaches with a Total Viral Challenge Strategy

Viral clearance is a critical component of the regulatory submission and approval process. These studies help to define the overall safety of a drug by looking at the capability of a manufacturer’s downstream purification process to eliminate potential viral contaminants…

Impact of Continuous Chromatography Mode on Protein A Resin Lifetime

Traditionally, Protein A chromatography is performed in batch mode using a single, packed column. In batch operations, antibody-containing samples are loaded onto the column at levels well below the total capacity of the resin to prevent sample breakthrough and subsequent product loss. However in recent years, continuous chromatography has emerged as an alternative to batch operations to improve productivity or increase resin capacity utilization of chromatography purification processes. Continuous chromatography by periodic counter-current chromatography (PCC) has been demonstrated to increase utilization of the chromatography resin capacity…

Increasing Downstream Bioprocess Efficiency and Overcoming Bottlenecks

Biomanufacturing is constantly evolving due to changing industry demands and new technologies that enable advancement. Industry goals are now primarily focused on reducing cost and improving throughput, productivity, time to market and flexibility. These goals must be met whilst maintaining the highest levels of product quality and safety requirements. With increased titer, downstream processes have had to manage higher titers and greater impurities than they were originally designed for. Thus downstream processes must also be improved to create an entire manufacturing process that is more streamlined and meets industry goals…

‘Jetting’ technology for manufacturing agarose beads with enhanced performance characteristics

The vast majority of chromatography resins designed for large-scale bioprocess chromatography separation are produced using traditional batch emulsification in conventional stirred-tank reactors. In these cases, the size of the beads formed in the reactor is a function of the shear force generated by the impeller. The faster the impeller speed, the smaller the beads are. As a result, there is a wide particle size distribution of the manufactured beads. Furthermore screening is required to remove coarse and fine beads, which detract from column performance. This screening is extremely time consuming particularly for smaller beads (less than 65 µm). The smaller the bead being produced the lower the achieved yield so realistically one cannot make beads financially viable less than 40 µm. It also adds high costs due to the additional time in the manufacturing facility with large volumes of waste from the fine and coarse beads. Even after this screening, the resin will still have a relatively wide size particle distribution…

Lowering MAb Clinical Trial Material Manufacturing Costs with Purpose-designed Protein A Chromatography Resins – A Case Study

The use of Protein A affinity chromatography is commonplace in biopharmaceutical manufacturing, with 95% of all commercially available MAbs using Protein A purification. High purity is achieved in one step (around 99%), but it is well recognized that the cost of Protein A resins is substantial. If a product makes it to marketing approval and manufacturing these costs are amortized over a large number of purification cycles and the contribution to cost of goods is acceptable. However, a high percentage of clinical projects will fail, resulting in the Protein A resin only being used for a small number of cycles – significantly reducing cost-efficiencies…

New KANEKA KanCapA™ 3G for Improved Binding and Milder Elution of Therapeutic Antibodies

Protein A is by far the most common purification method in biopharmaceutical manufacturing. Due to its high affinity and selectivity for therapeutic antibodies, high purity can often be reached in a single step. With the expanding market for therapeutic antibodies, pressure to reduce the cost of pharmaceuticals, and increases in upstream production titers; Protein A improvements have been required to meet industry demands for improved downstream purification efficiency…

Optimize Changeover Workflows with ÄKTA readyflux – An Automated, Single-use Crossflow Filtration System

In biomanufacturing process efficiency is key. This is particularly true in pilot and small scale manufacturing where frequent change-overs between product campaigns or batches is often required. Cleaning and validation during change-over can involve significant time, labor, water and utility costs. One way to optimize workflows is to use single-use technologies and another is to automate processes as much as possible…

Optimize downstream processing with single-pass inline concentration

Concentration of biological drug substances is an important step at various stages in biomanufacturing. Concentration is often necessary between chromatography steps, in post harvest, during pre-capture or for in-process volume reduction. Concentration may also be needed between chromatography steps. During concentration applications, there is a potential for aggregation, particularly with sensitive biologics even when they are only slightly stressed. Therefore, an effective concentration system must operate efficiently under mild conditions while at the same time being flexible enough to integrate readily with different downstream operations…

Pre-activated Resins for Ligand Immobilization to facilitate the Creation of Customized Affinity Purification Media

In the development of biopharmaceuticals there are times when an off the shelf affinity chromatography medium is unavailable or isn’t highly selective for the target molecule being purified. It is possible then to design a custom chromatography solution by coupling a specific ligand to a pre-activated resin…

Protein A Chromatography – A look at where we have been and where we are going

In this podcast and accompanying article, we interviewed Jonathan Royce,  Business Leader, Chromatography Resins, GE Healthcare Life Sciences, about the evolution of Protein A including the latest developments in Protein A chromatography resins. We also discussed what the future holds for this purification mainstay and how it can continue to address the changing needs of biopharma.

Resolving large scale buffer management challenges

In this podcast and accompanying article, we interviewed Joakim Lundvist, Modality Manager, BioProcess™ Hardware, GE Healthcare about large-scale buffer management challenges. Buffer preparation is known to be one of the most resource-intensive activities in biomanufacturing as large volumes of buffers and process liquids are often required. So how can this be done in a more efficient way? How can more capacity be added to buffer preparation without adding major capital investment? Are there ways to reduce the manufacturing footprint and time spent on buffers? We examined the biggest challenges in buffer management and explored how technologies like inline conditioning can provide possible solutions…

Scale up with confidence – Introducing ReadyToProcess 32 L (450/200)

To reduce costs, increase flexibility and shorten time to market, the use of single use and disposable technologies have increased significantly in biopharmaceutical development and manufacturing. In downstream processing prepacked chromatography columns reduce the need for time consuming cleaning validation and column packing. The last few years has seen a steadily increasing implementation of prepacked chromatography columns in process development and clinical manufacturing. Many of these projects are now scaling up for commercial production…

Subvisible Particle Characterization: Why Simply Counting Shadows Leaves You in the Dark

Significant advances in analytical technology over the past few years have improved the quantification and characterization capabilities for subvisible ( 1 – 100 µm) and submicron particles (≤1 µm). As the technology continues to improve so do the expectations of regulatory agencies for sponsors to characterize particles in these size ranges. However, multiple orthogonal methods are required to span the entire range and accurately characterize the particle profile. Each instrument has its own limitations based on detection method and properties of therapeutic protein products that must be well understood to generate high quality data. KBI Biopharma has extensive experience with particle detection methods, as well as, in-depth particle data analysis. KBI’s Particle Characterization Core team can help choose appropriate orthogonal particle to combine in order to accurately quantify, characterize and identify particles in specific therapeutic protein products for all size ranges based on clients’ needs…

Don’t miss our Top 30 Cell Culture Dish Blogs of 2017