This week’s headlines include: Alexion fortifies rare blood disorder drugs business with Achillion deal, Drugmaker to Test Machine Learning to Prevent Drug Shortages, Congo to start using J&J Ebola vaccine in November, Marrying CRISPR with immuno-oncology to defeat remote tumors, and Better Antibody Validation Approach Should Improve Critical Research Studies.

Podcasts:

Check out our podcast channel. We have over 30 great podcasts covering drug discovery, stem cell culture, upstream and downstream biomanufacturing and more! Click below to download from iTunes or Google play:

In Case You Missed It, Recent Articles on Cell Culture Dish and Downstream Column:

Ultrafiltration for Protein Concentration – Centrifuge and Crossflow Solutions

We recently finished our Ask the Expert discussion on “Laboratory based therapeutic and diagnostic marker protein concentration through centrifugal and crossflow ultrafiltration”. Ultrafiltration is an important tool in concentrating therapeutic and diagnostic marker proteins. Efficacy of ultrafiltration processes can be very application dependent and thus may raise technical questions in process planning. Two of the primary methods are using centrifugation or crossflow ultrafiltration. When considering the ultrafiltration method that is best for your application, it is critical that you select the appropriate method for target recovery and sample volume, while still considering speed and efficiency. During this Ask the Expert session, we covered topics related to ultrafiltration of large sample volume concentration, sensitive proteins and protein degradation, when to use cassettes vs. centrifuge, viral vector concentration, membrane selection and non-protein concentrations…

Raw Material Quality – Identifying and Mitigating Variation

In this podcast, we interviewed Cory Card, Principal Scientist Life Sciences, GE Healthcare about raw material quality, its impact on cell culture and technologies to identify and mitigate raw material variation…

Ask the Expert – Laboratory based therapeutic and diagnostic marker protein concentration through centrifugal and crossflow ultrafiltration

Efficacy of ultrafiltration processes can be very application dependent and thus may raise technical questions in process planning. To answer these questions, this week we are excited to have Rik McRae, Technical Manager for Operations, Sartorius Stedim Lab, Ltd. as our expert. Rick has over 20 years of experience in product and application research and development, production engineering and technical guidance and is currently a member of the Sartorius lab ultrafiltration team. Rik is a subject matter expert for technical support and application knowledge, with strong expertise in therapeutic protein, drug delivery nanoparticle, and diagnostic marker concentration applications, with centrifugal, pressure driven and lab scale tangential flow filtration systems…

Cool Tool – Vivaflow Crossflow Cassettes provide plug and play target molecule concentration systems that are scalable for a wide range of sample volumes

Ultrafiltration is an important function in many labs. While there are many ways to conduct concentration and filtration, it is critical that you select the appropriate method for target recovery and sample volume, while still considering speed and efficiency. Sartorius has launched its Vivaflow Crossflow Cassettes with these requirements in mind. With three products specifically designed to meet different customer requirements, they provide a simple to use, plug and play system for concentrating a wide range of sample types, over volumes from 0.1 liter to 5 liters, with high reliability and consistency of results…

Improved Protein yields in CHO and HEK293 cells using a dedicated transfection reagent: FectoPRO®

Transient gene expression (TGE) is commonly used for medium scale production of recombinant proteins and antibodies. This approach allows generation of sufficient protein amounts without an investment in production of stable cell lines prior to “proof of concept” studies or tools validation. The speed and flexibility of the process has enabled TGE to be widely adopted in bioproduction for early discovery, research applications and process development…

Novel affinity resins enabling the purification of next generation antibody fragments: KANEKA KanCap™ G and KanCap™ L

Ever since the licensing of first monoclonal antibody (mAb) drug, biologics have seen unprecedented growth as drugs to treat a variety of malignancies¹. The modular structure of mAbs have allowed protein engineers to create smaller, nimbler, and multispecific next-generation antibody therapeutics. Some of these modalities can be easily produced using microbial expression systems, offering higher yields and excellent process economy²…

Supplier Qualification and Material Selection – A Case Study of Biopharmaceutical Resin Manufacture

To ensure a safe and continuous supply of life-saving biopharmaceuticals, raw materials for biomanufacturing must be selected carefully and suppliers evaluated with much scrutiny. Several instances of drug shortages as the result of either a raw material shortage or contamination reinforce the need for thorough evaluation. Ensuring a reliable supply and the quality of the materials selected is of paramount importance…

Bioburden Control Strategies for Continuous Downstream Processing

Implementing continuous bioprocessing for biomanufacturing has been increasing in interest. As a result, questions have arisen about the implementation of this strategy for downstream processes. Of particular interest is maintaining a high degree of bioburden control in continuous downstream process. While bioburden control strategies for continuous processing focus on prevention, not unlike batch processing, many want to know if there are specific strategies that should be implemented with continuous bioprocessing that are different than those used in batch processing…

Cool Tool – Innovative sorbents enable a robust and streamlined protein purification process

Monoclonal antibodies have long been purified using a platform approach. This platform mainly consists of three chromatography steps. These include a Protein A based affinity chromatography step followed by polishing steps. The purpose of the affinity chromatography is to capture the mAb, while the polishing steps remove any remaining impurities, such as residual DNA, host cell proteins, viruses and aggregates. There are options in the selected polishing steps, but often they involve cation exchange or hydrophobic interaction. Increasingly membrane chromatography is being used as a polishing step to remove any remaining contaminants…

Optimizing mAb Purification with Highly Selective Mixed-mode Cation Exchange Sorbent

In today’s market, mAbs are produced for several therapeutic applications, yet they are not a homogeneous family of products. Each mAb is unique, based on its isoelectric point, hydrophobicity and ability to aggregate; the contaminant HCP content is also process-dependent. As drug manufacturers seek to produce mAbs for various application, they are also looking to streamline processes for efficiency and quality…

Trainings:

Eppendorf Bioprocess Workshop

Implementation of an Affordable and Scalable Manufacturing Strategy for Gene Therapy
Upstream bioprocess development is an integral part of gene therapy product development. Cell culture bioprocess development is usually carried out at small working volumes. This helps save time and resources, because several experiments can be conducted in parallel, costs for media are kept low, and relatively little laboratory space is required. When more material is needed for characterization, trial runs, and finally for commercialization, biopharmaceutical companies transition the process to bench scale and then up to pilot or production scale. In this presentation, we will present bioprocess solutions for parallel process development at small scale. Furthermore, we will discuss bioreactor scalability and address several scaling approaches.

A Beginner’s Guide to Bioprocess Modes – Batch, Fed-Batch, and Continuous Processing
We will discuss the differences between batch, fed-batch, and continuous fermentation and how these influence culture growth. As an example, we look at E. coli fermentation processes at bench scale. We track the biomass and nutrient concentrations during batch, fed-batch, and continuous fermentation runs. We explain different methods to analyze the process, including determination of biomass, growth rate, productivity, yield, and analysis of process costs. The  comparisons can help bioprocess engineers to select the most appropriate method to meet their needs.  In our examples we studied E. coli fermentation at bench scale. The principles may also apply to bioprocesses using other microbes or mammalian cells, at both smaller and larger scales.

BTEC, NC – Wednesday, November 6, 2019 – Click here for information on North Carolina workshop

Conferences:

Headlines:

“Alexion fortifies rare blood disorder drugs business with Achillion deal,” Reuters

“Alexion Pharmaceuticals Inc (ALXN.O) on Wednesday agreed to buy smaller biotech Achillion Pharmaceuticals Inc (ACHN.O) in a deal initially valued at $930 million, as the company looks to retain its leadership in treating certain rare blood disorders. Alexion, which is paying a 73% premium, is eyeing Achillion’s two experimental treatments for the rare blood disorder, paroxysmal nocturnal hemoglobinuria (PNH), a market it has dominated with its flagship drug Soliris…”

“Drugmaker to Test Machine Learning to Prevent Drug Shortages,” The Wall Street Journal

“Merck KGaA plans to use analytics and machine learning to predict and prevent drug shortages, a move that could also save it money. Currently, the Germany-based pharmaceuticals company needs to stockpile medications to make sure it has enough on hand, meaning some of them expire before they can be used. Merck said its supply-and-demand forecasts are about 85% accurate today…”

“Congo to start using J&J Ebola vaccine in November,” Reuters

“Health authorities in Democratic Republic of Congo will introduce a Johnson & Johnson Ebola vaccine in November in the country’s eastern provinces, to counter the current outbreak, they said. The J&J vaccine will complement another vaccine manufactured by Merck, which has been administered to more than 225,000 people. It requires two injections eight weeks apart, unlike the Merck vaccine, which requires a single shot…”

“Marrying CRISPR with immuno-oncology to defeat remote tumors,” FierceBiotech

“Immuno-oncology drugs like Merck’s PD-1 inhibitor Keytruda work by blocking certain proteins cancer cells use to evade detection and destruction by the immune system. But, often, cancer cells can use other molecular disguises to escape the immune attack, rendering the drugs ineffective for many patients. Scientists at Yale University have come up with a solution to this problem, and it involves combining the gene-editing system CRISPR with a type of gene therapy designed to help the immune system find tough-to-spot tumor cells. The technology doesn’t cut segments of DNA and replace them, but rather it hunts for tens of thousands of cancer-related genes. Whenever it finds cells that have them, it marks them so the immune system can recognize them…”

“Better Antibody Validation Approach Should Improve Critical Research Studies,” Genetic Engineering News

“A team led by Peter McPherson, PhD, at the Montreal Neurological Institute and Hospital (The Neuro) published a study (“Implementation of an antibody characterization procedure and application to the major ALS/FTD disease gene C9ORF72”) in eLife that points to the need for better antibody validation and outlines a process that other labs can use to make sure the antibodies they work with function properly. Antibodies are used in laboratories and clinics to study proteins, which are the biomolecules that translate information from an organism’s genes into the structure, function, and regulation of its tissues and organs. Genetic mutations can cause protein imbalances or malfunctions, leading to human disease…”