I have compiled a list of our most popular 15 Blogs for 2013. Here are the top blogs in alphabetical order.
I have been peripherally aware of 3-D printing for various industries. I know that architects can use it to create scale models of buildings, the car industry can use it to create part prototypes and prosthetics are even printed for use in healthcare. Although, I may be cell biased, to me the most exciting use for 3-D printers is to print living tissue.
Advances in Adherent Cell Culture Approaches Abound – Promoting Progress in Production Performance for Attachment Dependant Processes
Large-scale adherent cell culture is required in such processes as vaccine manufacturing; cell-based therapies (including stem cell); cell replacement and tissue repair. The vaccine industry is completing its move from production in animal and primary tissues (such as embryonated chicken eggs) to cultured cell-based platforms. A number of adherent animal cell types are used by vaccine manufacturers, including mammalian and avian lines for both viral and the newer “viral-vectored” vaccines. Many animal and human vaccines are produced in attachment-dependent cells such as VERO, MDCK or chick embryo fibroblast (CEF) cells. Some of the established adherent lines have been used for decades in classic production formats. The viruses used for such work range from clones of influenza to recombinant lentivirus, baculovirus or alphavirus.
The translation of a research-grade cell culturing process into a scalable, clinical-grade manufacturing protocol is not a simple one. There are many attributes of the culturing process that are crucial for manufacturing, yet are often overlooked by inexperienced Cell Therapy developers. These include, but are not limited to, cell characterization, feed strategy/media optimization, and closed system processing. Here, topics are discussed that should be considered when converting a promising preclinical finding into a scalable process that could be used for the commercial scale manufacture of cell-based products. The topics being discussed are applicable for both autologous and allogeneic cell-based products.
Genetic Engineering News recently published an article titled “Top 20 Best Selling Drugs of 2012,” in which they laid out the top sellers for last year. Of the top twenty spots, eight were captured by biologics. Other highlights for biologics included: The top three best selling drugs were biologics – Humira, Remicade and Enbrel, and all are involved in the treatment of arthritis. Every biologic on the list had sales that were up in 2012. The biggest sales increases were for Lantus (Sanofi) with an increase in sales of 19.3% and Humira (AbbVie) also up 19.3% from last year. Biologics to treat cancer were also at the top of the list with Roche’s Rituxin, Herceptin, and Avastin in fifth, seventh and nine place, respectively.
In my previous blog “Innovative Products from the ASCB Conference – Part I,” I highlighted a new product from Life Technologies – the Expi293 Transient Expression System. Launched last September, it combines specialized media, lipofectamine technology, and molecular biology to create a transient transfection system with titers that approach stable expression system yield. Everyone knows that stable expression systems provide the greatest chance for high expression of proteins; of course the downside is significant time (weeks or months), and resources to develop this type of system. While obviously necessary if moving to large- scale manufacturing, stable expression systems are not usually suitable for early drug discovery and development. The time necessary to develop a stable line would slow drug discovery and development by delaying go/no-go decisions and committing valuable resources to proteins that are still unproven.
In the formative years of cell culture, many referred to it as more art than science. Most likely, a response to the finicky nature of cells, inconsistent results and a lack of understanding about the science behind cell culture. As technological advancements occurred in cell culture, things like prepared media, biological safety cabinets, and disposable plasticware, scientists had time to think about other things beyond the best cell culture practices. In addition, the trend up until recently was mostly to use robust and easy to use cells like the HeLa line, which due to its robustness, eliminated the need for deep study and careful training on the delicate nature of animal cell growth. As a result, for the most part hands-on training in cell culture does not exist. If training does occur, it is usually by the ancient oral tradition of lab-lore which leads to the “how” but not the “why”. This lack of specific training in both how and why allows for the perpetuation of incorrect information and makes troubleshooting impossible.
There have been many improvements made in biopharmaceutical manufacturing since its inception in the 1980’s. This has culminated in the most common approach to large-scale biopharmaceutical manufacturing being the fed-batch mode applied to suspension culture. Improvements made to the process have involved each of the individual steps, including advances in cloning and selection methods, removal of animal products materials, implementation of single use systems and improved purification resins and columns. This isn’t to say that other approaches haven’t been tried, even with great success. For example, Genzyme (Sanofi) and Centocor (J&J/Janssen ) have long employed perfusion culture in upstream processes of some approved biopharmaceutical manufacturing. Nevertheless, the overall paradigm of batch-fed process throughout the industry has not evolved a great deal.
Last week, The Dish posted a blog titled “Biologics Have a Robust Pipeline According to Latest PhRMA Report,” where we discussed highlights from the Pharmaceutical Research and Manufacturers of America’s new report, “Medicines in Development – Biologics, 2013 Report.” In the report, 69 cell therapies were identified as having clinical trials under review with the Food and Drug Administration (FDA), including 15 in Phase III clinical trials. Of the therapies listed, nine therapeutic categories were represented and include: cardiovascular disease, skin diseases, cancer and related conditions, digestive disorders, transplantation, genetic disorders, musculoskeletal disorders, eye conditions, and other. The purpose of this blog is to give an overview of these therapies, the diseases states they are treating, the technologies they employ, and the companies who are working to bring these products to market.
Although few cell therapies are currently available to patients, Cell Therapy Group estimates that there are 37 cell therapies currently in late stage clinical development. [i] Many of these are likely to be positioned for FDA review in the next few years. However, as the industry makes important progress in clinical research, several aspects of Cell Therapy development continue to present considerable challenges for large scale commercialization. One current challenge is that the production of cell therapies typically carries higher manufacturing risks than the production of small molecule pharmaceuticals, especially as production is ramped up to meet broader demand. Most cell therapies present significant risks of manufacturing errors or contamination issues, which can stop production entirely or affect efficacy and patient outcomes. Most cell therapies also have a relatively short shelf life, which can put additional pressure on production and distribution schedules. The cell manufacturing process must also meet both FDA regulations and the requirements of a successful business model. Companies developing cell therapies must identify the optimal strategies to transition to commercialization without compromising quality.
Cell-based therapies are gearing up to have extensive impact on the healthcare field in coming years. With a promise for treating various diseases, and long-term conditions like heart disease and metabolic disorders, stem cell therapies are gaining valid appreciation as a viable alternative to traditional methods. In fact, the overall U.S. market for stem cell products is predicted to reach as much as $6 billion by 2020, according to research from Robin Young Consulting.In order to capitalize on the potential of these therapies, there must be efficient methods for growing the adherent stem cells necessary for developing subsequent treatments. In the simplest terms, a proper surface is required that enables cell growth and harvest. In the lab phase, the focus is on producing the expected cell without much concern over cost or volume. However, when moving to a larger scale, cost becomes a significant issue, driving the need for manufacturing technology with an emphasis on safety, reproducibility and adherence to GMP standards.
The bioreactor is the cornerstone on which cell culture for biopharmaceutical production is based. The bioreactor should provide an efficient means to expand the cell culture and to repeatedly deliver a product with the desired quality attributes. Choosing the right bioreactor is vital, but how do you know which bioreactor is the most suitable for your applications? From the early-day use of glass flasks in research and stainless steel vessels in manufacturing, the bioreactor has come a long way. A fundamental change in bioreactor technology is the shift to disposables. Although the use of stainless steel vessels still prevail at the very large manufacturing scales, single-use options are increasingly common in culture scales up to 2000 L. The benefits with disposables are now widely acknowledged for both upstream and downstream applications. Single-use equipment offers increased flexibility with quicker set-up and changeover between runs, and reduces the need for costly and time-consuming cleaning and cleaning validation operations.
The University of Pittsburgh Graduate School of Public Health has examined over 100 years of health records to compile a very interesting and compelling study that supports vaccination efforts. The study, “Contagious Diseases in the United States from 1888 to the Present,” was published in the New England Journal of Medicine and focuses on comparing pre-vaccine health records with post-vaccine health records for seven major diseases, including polio, measles, rubella, mumps, hepatitis A, diphtheria and pertussis (whooping cough). By looking at the pre-vaccine data, they were able to project the number of cases that would have occurred if the vaccine had not been invented. Using this method they estimate that U.S. childhood vaccine programs have prevented more than 100 million cases of disease.
In the biopharmaceutical industry there is an ever-present drive to increase product yield and reduce cost. The industry is driven in this direction, not only by the drive to improve manufacturing techniques, but also by pressure from the government, physicians, and patients to reduce the overall cost of medications. However these cost savings must be achieved without compromising high safety standards. Since the inception of biopharmaceutical manufacturing in the 1980’s there have been continual improvements to the process. These improvements have culminated in the most common approach to biopharmaceutical manufacturing, fed batch suspension culture, most commonly expressed in CHO cells. While improvements have continued in areas including advancements in cloning, media formulation, removal of animal components, and downstream purification resins and columns, there has been little change to the actual fed batch paradigm. One technology that could perhaps make a big change in how biopharmaceuticals are manufactured is the use of perfusion bioreactors. Perfusion technology has improved extensively since its creation and its application to large-scale manufacturing and other applications in the production of biologics deserves a second, closer look.
A critical feature of a bioreactor system is the technology used for mixing. Different aspects of mixing and mixing technologies have been extensively studied in conventional bioreactor systems made of glass or stainless steel. However, the design proven in conventional systems is not always directly transferrable to a single-use format without modifications. Hence, it is necessary to understand the interrelation between the physical features of a bioreactor system and how these features ultimately affect the performance of the system.
Last week there was an article in Fierce Biotech Research titled “Doctor Calls for Boost in Cord Blood Stem Cell Research,”the article describes the potential of cord blood cells and discusses some of the areas where cord blood is being studied as a treatment for disease. I decided that this presented a good opportunity to revisit the subject on The Dish and to outline some of the current uses of cord blood, clinical studies, and research opportunities along with a discussion of potential hurdles to success.