Biomanufacturing capacity is in demand, particularly with several biologic drugs entering final phases of the clinical pipeline. Capacity could quickly become in short supply if many of these drugs receive approval. One way to combat capacity crunches is to improve production and yield. Last week, I wrote a blog describing how CHO cells are the expression system for four out of five of the best selling biologic drugs. The blog titled “CHO Cells – the Top Expression System for Best Selling Biologic Drugs” posed a question on whether CHO production could be improved or whether we had hit peak performance. Since CHO cells are currently the top expression system for biologic drugs, it makes sense to look at ways to improve their productivity and ultimately conserve capacity….
Ever since hybridoma technology was discovered in the 1970’s, scientists have been improving the technology. They have worked to enhance the antibodies themselves by improving the way they are accepted by the human body and reducing side effects. Through genetic engineering scientists have been able to move away from a final product that is full mouse antibody, to a chimeric antibody (about 33% mouse and 67% human) and now some companies are manufacturing humanized antibodies (generally 5-10% mouse and 90-95% human). In addition to improving the genetic make-up of the antibody, work has continually been done to improve manufacturing techniques and antibody yield. In this blog we will look at three areas in the process where antibody production can be improved….
With several new stem cell therapies in development and many showing promising results in clinical studies, it is critical to begin moving stem cell manufacturing from small scale to large scale manufacturing for therapeutic use. Several of these potential therapeutic applications will require billions to trillions of stem cells per lot and manufacturing will need to expand to meet these demands. New technologies have been created to successfully culture large numbers of stem cells in a single batch….
A recent article in Pharma Times titled “US biopharma: nearly 300 vaccines in R&D,” points out that there are currently 300 vaccines either in clinical studies or under review by the Food and Drug Administration (FDA). While not all vaccines are cell culture derived vaccines, it does indicate that a large number of cell culture based viral vaccines are in the pipeline and that perhaps viral vaccine manufacturing should be examined. One area under consideration is how to improve viral yield so that vaccines can be made at lower cost and therefore available to more people. Viral yield is also very important when dealing with a pandemic because the higher the titer the more available the vaccine becomes to needy people. . During the last pandemic, the H1N1 outbreak in 2009, most vaccine manufacturing was egg-based and reports of low yields were common. When yields are low, it leads to shortages and delays in distributing vaccine to prevent significant public health risks. This indicates the critical importance of maximizing viral yield, regardless of the manufacturing host system. Now that cell culture based flu vaccines have been approved in Europe, cell-based viral yield will be crucial to prepare sufficient doses in case of another influenza pandemic….
In the biopharmaceutical industry there is an ongoing discussion about manufacturing capacity vs. demand for biologic drugs. Recently there has been increased concern because several biologic drugs have entered the final phases of the clinical pipeline. If many of these drugs receive approval, capacity could quickly become in short supply. The most common way to increase capacity is to build or expand manufacturing facilities to accommodate more or larger bioreactors. The problem with this approach is that expansion takes a great deal of time and capital upfront before manufacturing can begin. In addition, this approach is not scalable. This means that once the facility is built, it takes money to operate even when no drugs are being manufactured there. If for some reason demand goes down on any of the drugs, companies can find themselves with a lot of costly extra capacity. There is a fine line between not having enough capacity and having too much….
In this blog we will review ten companies that have made significant progress with stem cell therapies in clinical trials. The purpose of the blog is to give an overview of stem cell therapies in clinical trials, the diseases states they are treating, the technologies they employ, and the companies who are working to bring these products to market. We will look at five companies in part I and the remaining companies in part II….
Polystyrene has always been a good choice for cultureware because of its optical clarity, its ability to be molded into many vessel types and the fact that it is fairly inexpensive. The major disadvantage is that it is hydrophobic and not a very hospitable surface for cell attachment without treatment. Over the years, polystyrene modifications were developed to promote better cell attachment. Modifications can be chemical or physical and each offers specific advantages. One common treatment is gas-plasma treatment, also called tissue culture treated. These modifications worked quite well for the majority of cell types when grown in serum supplemented media. Difficult to attach cell lines required coating of the plate with biological extracellular matrices. More recently there has been a large movement toward animal-free cell culture, which prompted the need for more advanced cell culture surfaces. Thus. a new generation of cell culture surfaces was born to address more specific cell needs and to allow for culturing of the most difficult cell lines in a reduced serum or serum-free environment….
In May, Osiris’, Prochymal, received approval for a new stem Cell Therapy. The approval was first received in Canada, then New Zealand and is currently under review by the Food and Drug Administration (FDA) in the United States. Prochymal is a treatment for acute graft versus host disease. In addition, there are weekly reports of new stem cell therapies in development and many are showing promising results in clinical studies. With these advancements, it is logical to wonder how these stem cell therapies will progress from small scale manufacturing to large scale manufacturing for therapeutic use….
Stem cells can create systems to mimic healthy cells or diseased cells and by using these systems, companies can evaluate cell response to different drug candidates early in development. Studies using stem cells can identify new therapies, detect toxicity, and can help in evaluating effective dosing….
With a large number of cell culture based viral vaccines in the pipeline, manufacturing capacity will need to be maximized and the best way to achieve this is to increase yield and make manufacturing more efficient. Another advantage in increasing yield is cost reduction, which means that vaccines are more accessible to the developing world. In addition, manufacturing time is also decreased, which is critical in the case of a pandemic….
While mammalian cell alternatives to CHO based biomanufacturing are making a case, CHO still remains the most common cell line for best selling biologics on the market today. In a previous blog “CHO Cells the Top Expression System of Best Selling Biologic Drugs,” we discussed the manufacturing cell lines used in the top five best selling biologics of 2010. In 2010, four out of the top five best selling biologics used CHO cells for manufacturing. In 2011, according to Huggett and Lähteenmäki (2012), the top ten best selling biologics were Humira, Enbrel, Rituxin, Remicade, Avastin, Herceptin, Neulasta, Lucentis, Avonex and Rebif. Of these, seven are manufactured using CHO cell lines….
FDA has attributed higher approval rates to the use of FDA programs including Fast Track, Priority Review, and Accelerated Approval. FDA has also been successful in improving the approval process by streamlining reviews, increasing communication with drug companies during the review process, and meeting review deadlines. The FDA continues to lead the world in the first introduction of new active substances. According to the report “Over the past decade, roughly half of the new active substances launched anywhere on the world market were approved in the United States (see Figure 1). This year’s approvals contained ground breaking drugs in cancer and cystic fibrosis and also some firsts including the United States’ first approved drug from cord blood and first approved drug manufactured using genetically engineered plant cells….