This week’s headlines include: Measles Outbreak Now at 880 Cases, With Fastest Growth Still in New York, CRISPRed B Cells Produce Antibodies Against Hard-to-Treat Viruses, Merck buys Peloton to expand its kidney cancer treatment portfolio, FDA to Launch Expanded Access Pilot ‘Project Facilitate’ by End of May, Miniature livers reveal behavior of common cancer-causing gene mutation, and Lymphoma Resistance Mechanism to Chemo Drug Identified.

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:

Next Generation Cell Viability Analyzer Vi-CELL BLU Cell Simplifies and Speeds Workflow

Beckman Coulter Life Sciences just launched its next generation cell viability analyzer, Vi-CELL BLU. As part of the launch, Lena Lee, Global Product Manager for Vi-CELL was interviewed about improvements over the legacy analyzer. The Vi-CELL has been helping researchers for over 20 years to monitor the health of their cells by providing total cell concentration, percent cell viability, and cell size (another indicator of cell health)…

Minimize Cell Culture Contamination and Batch Failure by Creating a Closed System for Cell Culture Expansion

Batch failure due to cell culture contamination is a serious consideration for biomanufacturing. A recent BioPlan Associates Survey examined the frequency, cost and leading causes of batch failure. They found that on average a failure occurs every 9.4 months and costs companies $1 to $2 million. The leading causes of batch failure were contamination and operator error. It is logical that anytime the cell culture system is open, for instance when opening flasks during cell expansion, there is an opportunity for contamination…

End-to-End Integrated Manufacturing Solutions Enable Gene Therapy Commercialization

The past decade has seen a surge in the development of gene therapies. Currently there are over 1,000 cell and gene therapy clinical trials underway worldwide.¹ While the majority of current trials are still in Phase I or Phase II, there are more than 90 trials in Phase III. In fact, at last year’s BIO International Convention, Scott Gottlieb, Commissioner of the US Food and Drug Administration (FDA) stated that he expects the FDA to approve 40 gene therapies by 2022.²…

Transfection Reagent Portfolio Enables Seamless Scalability from R&D to Commercial Therapeutic Viral Vector Manufacturing

One common challenge in viral vector production is transitioning from research-based production to more rigorous quality and safety profiles for clinical and commercial manufacture. In fact, raw materials used in production at research scale are often not cGMP-compliant and therefore fit for clinical or commercial manufacturing. This means that critical raw materials frequently need to be replaced with cGMP grade material sourced from approved suppliers during process scale up. cGMP grade materials are manufactured under strict conditions and must pass rigorous testing. This higher manufacturing standard reduces the risk of introducing adventitious agents into clinical and commercial viral vector manufacturing…

Spheroid Cell Culture – Practical solutions for frequently asked questions

The past decade has seen an increase in publications recognizing the value of culturing cells in three dimensions (3D) and the use of these 3D cell culture models has shown utility in many areas of research from cancer biology to regenerative medicine. One of the most common 3D cell culture types is spheroids. Spheroids more accurately recapitulate the native in vivo microenvironment with respect to cellular function and response to drugs than more traditional two-dimensional (2D) models. That said, working with spheroids is not without its challenges. Many labs working with spheroids have run into technical hurdles incorporating them into existing cell culture workflows. Whether it is issues with handling or optimizing protocols to assaying cells in 3D, these obstacles can be overcome…

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…

Scalable Protein A Chromatography for High-Throughput Process Development

Process development is a critical part of biomanufacturing, but it can be very time and resource intensive. With recent industry initiatives around speed to market, process development is an area that could really benefit from high throughput solutions. One high-throughput process development tool for chromatography is the use of 96-well plates. These plate platforms permit automated screening of large numbers of conditions very efficiently and use only a small amount of material for testing. This platform is great for screening but requires bridging experiments to translate results to process scale. In addition, automating the 96-well process requires investment in liquid handling equipment in order to reach the full potential of the platform…

Utilizing High-Throughput Process Development Tools to Create a Purification Process for a Biosimilar Molecule

Biosimilar molecules have some unique manufacturing requirements that must be taken into account when planning process development. The requirements for process development typically require a good deal of selectivity, cost-efficiency and the need to meet aggressive timelines. These lend themselves to a process development approach that incorporates high throughput…

Designing a Viral Clearance Study – A Step by Step Tutorial

Viral clearance testing is a regulatory requirement and critical part of the overall approval process for all biologics. Viral clearance testing is performed at two points in biologics development. Before Phase I clinical trials, viral clearance studies are conducted to demonstrate the capability of a downstream purification process to eliminate potential viral contaminants…

Headlines:

“Measles Outbreak Now at 880 Cases, With Fastest Growth Still in New York,” The New York Times

There have now been 880 measles cases reported in this year’s outbreak, already the largest since 1994, federal health officials said on Monday. An additional 41 cases were reported last week, according to the Centers for Disease Control and Prevention. Of those, 30 were in New York State, which is having the country’s most intense outbreak, largely in Orthodox Jewish communities…”

“CRISPRed B Cells Produce Antibodies Against Hard-to-Treat Viruses,” The Scientist

“Vaccines prevent millions of deaths a year and have pushed some diseases to the edge of existence. Yet it’s proven highly challenging, if not impossible, to develop effective vaccines against a number of viruses. Despite decades of research, there’s no approved vaccine that offers long-term protection against influenza, Epstein-Barr virus (EBV), or respiratory syncytial virus (RSV), a widespread pathogen that causes respiratory tract infections. For RSV, for instance, high-risk infants receive monthly injections of synthetically produced antibodies to protect them in the short term…”

“Merck buys Peloton to expand its kidney cancer treatment portfolio,” Reuters

“U.S. drugmaker Merck & Co Inc on Tuesday agreed to buy Peloton Therapeutics Inc for $1.05 billion in cash, gaining access to the privately held company’s lead kidney cancer drug candidate…”

“FDA to Launch Expanded Access Pilot ‘Project Facilitate’ by End of May,” Regulatory Focus

“Ahead of the launch of a new pilot aimed at improving patient access to unapproved oncology drugs, dubbed Project Facilitate, the US Food and Drug Administration (FDA) held a public workshop on Thursday explaining its goals for the initiative and to discuss ongoing issues related to expanded access. According to Richard Pazdur, director of FDA’s Oncology Center of Excellence, the pilot will be rolled out towards the end of May…”

“Miniature livers reveal behavior of common cancer-causing gene mutation,” FierceBiotech

“The gene BAP1 is mutated in up to 20% of liver cancer patients, but just how the abnormality promotes the growth of liver tumors is a big unknown. Researchers at Hubrecht Institute and Radboud University in the Netherlands have created a new model that’s helping to shed light on the role of BAP1 in liver cancer…”

“Lymphoma Resistance Mechanism to Chemo Drug Identified,” Genetic Engineering News

“A collaborative study from researchers at the Moffitt Cancer Center and Dana-Farber Cancer Institute has uncovered a mechanism of drug resistance to Venetoclax^®, also known as ABT-199, a BCL-2 targeting drug commonly used to treat chronic lymphocytic leukemia and acute myeloid leukemia. BCL-2 is a protein that promotes cell survival and is highly deregulated in numerous malignancies. This deregulation can be overcome by treatment with ABT-199. However, many patients who initially respond to the drug eventually develop resistance and tumor recurrence…”