This week’s headlines include: The Stem-Cell Revolution Is Coming — Slowly, FDA Issues Long-Awaited Biosimilar Interchangeability Guidance, MilliporeSigma Opens Meglumine Production Facility in Spain, Biogen to pay Forward Pharma $1.25 billion to protect MS drug, ‘Biobead’-based TB vaccine shows potential in mice, Donors and Drug Makers Offer $500 Million to Control Global Epidemics, and A Superbug That Resisted 26 Antibiotics.
In Case You Missed It, Recent Articles on Cell Culture Dish and Downstream Column:
HEK293 cells are easy to grow in culture and commonly used for transfection to produce recombinant protein or gene products. Transfection of HEK293 cells is prevalent due to the fact that they are easy to transfect with high efficiency, and in the right culture environment, can achieve high levels of expression quickly. Two applications with widespread use of HEK293 cells are viral vector production for gene therapies and recombinant protein production.
As biomanufacturing processes become increasingly complex, the FDA has stressed the importance of their Quality by Design (QbD) and process analytical technology (PAT) initiatives in an effort to encourage more consistent manufacturing processes and product quality. A QbD approach provides a systematic look at bioprocess development, which attempts to predict unique challenges and address them in advance. A key aspect of QbD is defining critical quality attributes (CQA) and critical process parameters (CPP) and then monitoring these closely through the use of PAT. However a challenge in this approach is to ensure that the culture is being monitored precisely, so that critical process parameters can be maintained accurately.
Cell culture media optimization continues to play a critical role in both increasing titers and providing a mechanism for modifying protein quality. One way to optimize media is to include supplements that improve productivity or protein characteristics. As a result, there is an interest in developing novel animal-free supplements that can impact these processes for both mammalian and microbial culture. It is important to note that supplements chosen to enhance media can have dramatic effects, both positively and negatively, on productivity, growth and protein quality. This highlights the importance of understanding what the drivers of the cell culture process are in order to identify appropriate supplements.
As the Cell Therapy industry increasingly moves from research to clinical trials and commercial manufacturing, it is necessary to scale up manufacturing processes to meet increasing product demand. Clinical and commercial manufacturing also requires that the manufacturing process be compatible with quality and regulatory expectations to ensure safety.
I have compiled a list of our most popular 10 Blogs for 2016. Here are the top Downstream Column blogs in alphabetical order.
As part of our Boston Biotech Week 2016 coverage, we will be writing about some of the posters presented at the conference. One poster that caught my eye for downstream was presented by Oncobiologics and JSR Life Sciences, “Optimization of a Protein A Chromatography Process for a Herceptin® Biosimilar (Trastuzumab).” In the poster, Oncobiologics and JSR Life Sciences describe the steps taken in identifying the most efficient chromatography process.
Only 1 out of each 50 biopharmaceutical new product candidates makes it through the research phase into clinical trial testing and subsequently to the market. This high attrition rate is predominantly in the early development phases and is attributed to (I) undesired pharmacokinetics profile (39%), (II) lack of efficacy (30%), (III) in vivo toxicity in preclinical model (11%), (IV) adverse effect in humans (10%), and (V) other reasons, of which most commonly commercial arguments based on cost of goods (10%). It is therefore imperative that technologies become available that allow significant de-risking of biopharmaceutical product trajectories in the early research and development phase. The importance of this has been recognized by the field with the introduction of the “Design of Experiments” (DoE) approach, identifying critical quality attributes and performance attributes like yield, glycosylation, potency, and consumable costs of a manufacturing process. Owing to the DoE approach, scientists now have a tool to strategize the development of a novel product candidate. That said, it is often found that due to the complexity of many novel molecules, the number of parameters that need to be tested still requires vast numbers of experiments which are time consuming and costly.
Because Protein A is a valuable resource in any mAb purification strategy, companies often search for ways to improve the productivity of their affinity chromatography step. One strategy worth further investigation is variable column loading. By varying residence time (RT) over the loading phase, productivity from an affinity chromatography step can be significantly improved.
“In 2001, President George W. Bush issued an executive order banning federal funding for new sources of stem cells developed from preimplantation human embryos. The action stalled research and discouraged scientists. Five years later, a Kyoto University scientist, Shinya Yamanaka, and his graduate student, Kazutoshi Takahashi, re-energized the field by devising a technique to “reprogram” any adult cell, such as a skin cell, and coax it back to its earliest “pluripotent” stage. From there it can become any type of cell, from a heart muscle cell to a neuron.”
“MilliporeSigma opened a facility in Mollet des Vallès, Spain, dedicated to the manufacture of meglumine, an FDA-approved excipient for pharmaceuticals and a component of medical imaging contrast media. The facility, validated by the FDA, is the only location in Europe that manufactures meglumine, an amino sugar derived from glucose. The facility in Spain is solely dedicated to the production of meglumine, thereby ensuring continuity of supply to customers as well as meeting increasing demand for the excipient, said Andrew Bulpin, head of process solutions strategic marketing and innovation at MilliporeSigma. As an excipient, meglumine interacts directly with active pharmaceutical ingredients to increase solubility. Therefore, the manufacture of meglumine must meet the same stringent regulatory and quality requirements as active pharmaceutical ingredients (APIs), he added.”
“Biogen Inc said on Tuesday it would pay Forward Pharma A/S $1.25 billion to license the Danish company’s patents covering multiple sclerosis drugs, providing Biogen an insurance policy on future sales of Tecfidera, its blockbuster oral treatment for the disease. Biogen and Forward Pharma have been locked in a dispute over the patents for dimethyl fumarate, the key active ingredient in Tecfidera, which had sales of about $4 billion in 2016. While the deal gives Biogen a share of Forward’s intellectual property, the legal cases are ongoing.”
“While Bacillus Calmette-Guérin is the only approved tuberculosis vaccine, its variable efficacy, along with the rise of drug-resistant TB, means there is always room for an updated shot. A new candidate, based on “biobeads,” elicited an immune response in mice and could lay the path for a new approach to preventing the disease.”
Stung by the lack of vaccines to fight the West African Ebola epidemic, a group of prominent donors announced Wednesday that they had raised almost $500 million for a new partnership to stop epidemics before they spiral out of control.
“People keep asking me, how close are we to going off the cliff,” says Dr. James Johnson, professor of infectious diseases medicine at the University of Minnesota. The cliffside free fall he is talking about is the day that drug-resistant bacteria will be able to outfox the world’s entire arsenal of antibiotics. Common infections would then become untreatable.