I have compiled a list of our most popular 25 Blogs for 2015. Here are the top Cell Culture Dish blogs in alphabetical order.

10 Biologics on Best Selling Drugs List for 2014

Last month Genetic Engineering News published an article titled “The Top 25 Best-Selling Drugs of 2014,” where they listed the best selling drugs for 2014. Ten biologics were on the list and seven of the top eight best selling drugs were biologics. The top 10 are listed below…

3D Bioprinting – Research Successes, Challenges, and Future Possibilities

Bioprinting – an additive manufacturing approach to creating tissues in 3D (rather than the traditional 2D cell culture methodologies) – involves programming a robotic dispenser to deposit layer upon layer of biological and biocompatible materials (called “bioinks”) to create viable 3D tissue.

Though bioprinted organs like the one implied in Dr. Anthony Atala’s TED talk (“implied”, because it features not a living bioprinted organ but merely a suggestion of one) and even newly invented organs are (arguably) possible in the future, much of the current research focus is on smaller and more manageable pieces, like pharmaceutical testing tools. As with any industry in its infancy, standard practices are still evolving, and the hurdles faced in growing 3D tissues and organs are the subjects of exciting research all over the world…

3D Printing and 3D Bioprinting – Changing the Healthcare Landscape

According to a recent report, “Applications of 3D Printing 2014-2024: Forecasts, Markets, Players,” “The global 3D printing market will reach at least $7 billion by 2025, which includes a conservative estimate of $3 billion for bioprinting.” The ability to create three-dimensional (3D) models and prototypes has enabled advancements in many industries. As the use of 3D printing grows overall, the use of 3D printing and 3D bioprinting in healthcare applications is also increasing…

2014 FDA New Drug Approvals – 11 Biologics Receive Approval

Last month, the FDA released its report titled “Novel New Drugs 2014 Summary,” in which they discuss approvals that occurred in calendar year 2014. In 2014, the FDA’s Center for Drug Evaluation and Research (CDER) approved 41 novel new medicines, called new molecular entities or NMEs. The number of approvals in 2014 was up from 2013 with 27 approvals and up from 2012 with 39 approvals. In fact, in looking at approvals over the past ten years, 2014 had the most approvals overall…

Achieving control and reproducibility of cell culture by eliminating serum

Several recent articles highlight the problems with reproducibility and the associated implications for advancing discovery work in basic research and drug discovery. Cells are incredibly sensitive to their environmental conditions including but not limited to cell signaling factors in media. Switching batches of serum or growth factors can make all the difference in the world (1). Elizabeth Iorns, co-founder of the Reproducibility Initiative stated, “The lack of reproducibility in cancer studies is a major obstacle in the development of viable therapies to cure cancer”. She went on further to imply the need to verify cancer studies and institutionalize scientific reproducibility (3). While serum has been empirically used in cell culture its relatively undefined nature is rarely questioned. FBS provides unknown but required factors for replication not present in basal media like DMEM. Even though FBS has been the reagent of choice to overcome the challenges of culturing primary cells it comes with a curse; in addition to the few required factors, a kitchen sink of other factors are also present. Surprisingly serum is thought of as one reagent and this has been shown to be the case. However each lot of serum is an independent reagent with different characteristics than another lot of serum. This can be demonstrated when one lot of serum can support the growth of cells and the associated functionality while another can not. This dichotomy accounts for a portion of the difficulty in reproducibility…

Cancer Drug Market Continues to Grow and is Fueled by Significant R&D Focus and Clinical Pipeline

In May the report, Innovation in Cancer Care and Implications for Health Systems: Global Oncology Trend Report, stated that the global cancer drug market had hit $100 billion in annual sales and predicted that the market would reach $147 billion by 2018. Further, the report forecasts that by 2017, as a therapeutic area, oncology will receive the highest amount of spending by developed nations.

The report also goes on to state that the largest R&D therapeutic focus area is oncology with almost 2,000 products in the pipeline. This focus on oncology can also be seen when looking at the best selling biologics over the past three years (2012-2014) and in recent new drug approvals…

Cell Culture Media Optimization: Making the perfect magical potion

Current Cell Cultivation Strategies and Future Trends in the Ever Advancing Stem Cell Therapy Space – A Step by Step Guide In our first Cell Therapy blog of 2015, “Cell Therapy: Are we there yet?, some of the major cell types that are under commercial development as well as some of the key clinical indications were described. Although the vast curative potential of this expanding industry is exciting, new challenges are also becoming apparent for the Cell Therapy space. Primarily, how do you meet the demand for a consistently performing high quality cell product that is by nature extremely sophisticated and can be, depending on the cell type, susceptible to spontaneous changes that may affect product performance?

Cell Therapy: Are we there yet?

Current Perspectives and Future Directions of the Ever Advancing Stem Cell Therapy Space. The almost infinite differentiation ability of stem cells advocates the curative potential of numerous pathological conditions that arise from dysfunction or destruction of specific cell populations within the body. Recent years have witnessed an explosion of novel cell based-therapies and several companies are now immersed in clinical development and commercial scale up phases needed to bring these treatments to market. As these novel therapies inch ever closer to final approval and “prime time” use in the clinic, they are molding the industry for the development of future Cell Therapy products and simultaneously shaping the regulatory landscape that ensures cell product safety, reliability, and efficacy…

Closed Systems in Biomanufacturing Offer A Variety of Benefits

I recently attended IBC’s Biopharmaceutical Development and Production week (BDP) and was pleased to find talks focused on single-use technologies, flexible facilities, closed systems and continuous processing. These subjects are sometimes referred to as “biomanufacturing of the future,” because they represent a change in paradigm from traditional biomanufacturing. While we have covered single-use and continuous bioprocessing extensively on Cell Culture Dish in the past, we have not dedicated much time covering the benefits and opportunities associated with closed systems. This blog will attempt to provide a high-level review of some of the topics associated with closed systems and will provide several outside resources for readers who want to explore the topic in more detail…

Continuous Bioprocessing – The Biomanufacturing Model of the Future?

While attending IBC’s Biopharmaceutical Development and Production week (BDP), I was glad to find an entire session just on continuous processing technologies and implementation. We have covered continuous processing topics in the past on Cell Culture Dish, but I was interested to hear the latest developments in this area and also to hear some additional first hand accounts of implementing a continuous process including the benefits and challenges of such a system. This blog will provide a high-level overview of some of the topics associated with continuous bioprocessing and share some implementation examples in biopharmaceutical manufacturing…

Continuous Downstream Processing – A Tool to Address Key Manufacturing Challenges

A decade or more ago, companies were very focused on how to increase mAb titers, but that has shifted significantly as titer levels have steadily increased in upstream culture. Now downstream is facing challenges presented by rising titers and facilities that were designed for traditional batch processing and titers in the range of 5 g/L or less. Continuous processing has been shown to effectively increase productivity and facility utilization in several instances. Some reasons to consider a continuous process or semi-continuous option include addressing facility fit issues and improving facility flexibility and utilization. Product quality concerns, particularly for unstable products where delays in processing could negatively affect quality, can also be managed more effectively with continuous processing…

Culturing hPSCs: From MEFs to Naïve State Cells

Culture conditions for human pluripotent stem cells (hPSCs) have improved greatly since in vitro methods for culturing human embryonic stem (hES) cells were first described (1,2) (Figure 1). These initial methods relied on the use of mouse embryonic fibroblasts (MEFs) or feeder cells in combination with fetal bovine serum (FBS) supplemented media. (3) However, the prospect of clinical uses for these cells quickly resulted in a need for improved methods that eliminate these potentially immunogenic animal-derived components. Efforts to improve hPSC culture protocols have largely focused on removing the undefined and non-human components (4-6) of the system (Figure 1), leading to feeder-free culture methods that utilize a combination of growth factors (bFGF and/or TGF-β), a serum replacement in the medium, and cultureware coated with an extracellular matrix surface such as Corning® Matrigel®. (7-8) Subsequently, multiple publications have reported formulations for the maintenance of hPSCs in a defined, feeder-free, or xeno-free (i.e. devoid of animal components) manner. (9-12)…

The Evolution of Vaccine Manufacturing – Past, Current, and Future Trends

The vaccine industry is a robust industry that is growing substantially. According to a 2013 report (1) from the World Health Organization (WHO), the market has quadrupled from $5B in 2000 to almost $24B in 2013 and is expected to rise to $100B by 2025. The influenza vaccine market alone was $2.9B in 2011 and is expected to rise to $3.8B by 2018. The vaccine industry is also a driver of growth in the global pharmaceutical market with 10-15% growth per year vs. 5-7% for pharmaceuticals.

One reason for the projected growth in vaccines is due to the more than 120 new vaccine products in the development pipeline. Some of these pipeline vaccines are poised to have a major impact on global public health by targeting very deadly or widespread viruses. Examples include the vaccines in development for the Ebola virus. These vaccines have been receiving extensive coverage and have been fast tracked as a result of last year’s outbreak in West Africa. Other significant vaccines in development include vaccines for dengue fever, H5N1 (bird flu), HIV, Herpes Simplex Virus, Epstein Barr (mononucleosis), chikungunya virus, and the Marburg virus…

Exosomes: A Major Phenomenon Flying Under the Radar

It was discovered some time ago that eukaryotic cells regularly secrete such structures as microvesicles, macromolecular complexes, and small molecules into their ambient environment. Exosomes are one of the types of natural nanoparticles (or nanovesicles) that have shown promise in many areas of research, diagnostics and therapy. They are small lipid membrane vesicles (30-120 nm) generated by fusion of cytoplasmic endosomal multivesicular bodies within the cell surface. Exosomes are found throughout the body in such fluids as blood, saliva, urine, and breast milk. Furthermore, all types of cells secrete them in in vitro culture. It is believed that they have many natural functions, including acting as transporters of nucleic acids (mostly RNA), cytosolic proteins and metabolites to many cells, tissues or organs throughout the body. Much remains to be understood regarding how they are formed, as well as of their targeting and ultimate physiological activity. But many don’t realize that some activities have been rather thoroughly demonstrated─ such as their function in some sort of either local or more systemic intercellular communication…

The Future of Biopharmaceutical Manufacturing – Solutions to Address Industry Challenges

There are many challenges facing biopharmaceutical companies as they move a drug from discovery to commercial manufacturing. These challenges drive continual improvements in both manufacturing strategy and the associated tools or technologies used. Some challenges currently facing the industry include…

Hollow Fiber Provides a Sweet Spot for Several Biomanufacturing Applications

Since the 1980’s hollow fiber has been a popular choice in manufacturing products for the in vitro diagnostics market and was also used for the clinical manufacturing of whole cells (1, 2). Despite proven success in monoclonal antibody manufacturing, the use of hollow fiber bioreactors has not reached widespread use in biopharmaceutical manufacturing – yet. Evolving demands and trends in biomanufacturing coupled with improvements in hollow fiber bioreactor technology has created an opportunity for hollow fiber to provide unique advantages in biopharmaceutical, Cell Therapy, and vaccine manufacturing…

Improving Continuous Process Efficiencies Through Development of a High-Performing Perfusion Media

The biopharmaceutical industry has a growing interest in continuous processing as a way to improve manufacturing efficiency and facility utilization. One reason is that continuous processing has proved a very successful manufacturing model in many other industries. Furthermore, certain continuous technologies have already been incorporated into existing biopharmaceutical manufacturing with many benefits. One continuous process technology that is currently being utilized in some commercial biopharmaceutical manufacturing is perfusion culture…

Intestinal Organoid Culture: a Convenient and Physiologically Relevant Model for Intestinal and Stem Cell Research

Intestinal epithelial organoids are functional three dimensional (3D) models of the intestine that are novel and exciting tools for research across multiple disciplines including intestinal biology, adult stem cell biology and immunology. The 3D multicellular structures of intestinal organoids retain key physiological features of an intestine: the crypt and villus domains, a functional lumen and all of the major cell types present in the adult intestinal epithelium. The organoid culture can be passaged, expanded and frozen, and can be genetically manipulated via transfection of DNA or siRNA, or infection with an adeno- or lentivirus. As the organoids contain intestinal stem cells that rapidly divide and differentiate, this culture system is a convenient model for researching regenerative therapies. By bridging the gap between currently applied in vivo and in vitro methods, intestinal organoids are allowing scientists to ask and investigate questions that were not previously possible…

Is Now the Time to Move Your Research to 3D Cell Culture? Key Considerations and New Tools to Ensure Success

Mammalian cell culture has been used in research and drug discovery for many years. The use of this technology has resulted in many key discoveries in developmental biology, disease modeling, large-scale protein production, tissue engineering, stem Cell Therapy and lifesaving therapeutics. Traditionally, for adherent cell types, this work has been done in 2D culture as this was both easier to set up and maintain. 2D culture has since become standard practice. However, 2D culture has limitations, primarily the inability to mimic in vivo conditions of the cellular microenvironment and thus provide accurate physiological relevance…

A Look at the State of Cell Therapy – Current Manufacturing Options and Opportunities for Further Advancements – Part I and Part II

The Cell Therapy industry is still young but has already generated significant interest and excitement around the potential therapeutic value of its products. As a developing industry, there are still many challenges related to large scale manufacturing that need to be addressed. At the moment there are only a handful of companies readying themselves for large-scale commercial manufacturing, but the industry pipeline is impressive and sizable…

Materials and Assay Systems Used for 3D Cell Culture

Mammalian cell culture has served as an invaluable tool for cell biology research. Monolayers of adherent cells grown on flat and rigid two-dimensional (2D) substrates, such as polystyrene or glass, have evolved as a standard approach for conventional cell culture. 2D cell culture studies have played a pivotal role in furthering our understanding of developmental biology, tissue morphogenesis, disease mechanisms, drug discovery, large-scale protein production, tissue engineering, and regenerative medicine. However, there are inadequacies and limitations associated with 2D culture systems, especially regarding their inability to emulate in vivo conditions and provide physiological relevance…

A New Model for Continuous Processing in Downstream Purification

Continuous processing has certainly been a hot topic of late, and while most companies are not ready to move to a fully continuous process, many are investigating how incorporating components of continuous processing could improve their manufacturing…

Quality by Design – Maintaining Strict Control of Bioprocess Conditions

For QbD to work effectively you must be able to maintain tight control of your bioprocess conditions and that can be achieved through reliable analytics, characterization of influencing factors, minimizing user interference and early detection of deviation. As a result there is a need for tools to achieve these goals. One important method is to collect regular samples and monitor the substrates and metabolites using a metabolite analyzer. This provides routine updates on how the culture is performing…

Small Molecules in Stem Cell Research

Although their use in Stem Cell Research is quite recent, small molecules have long been associated with biological discoveries. Our understanding of biological processes often develops from discovering or designing ways to perturb a given process and observing the subsequent effects. While genetic and cytokine/protein-based approaches have been widely used for this purpose, small molecules offer some distinct advantages…

Stromal Cell Isolation from Adipose Tissue

Multiple preclinical studies have demonstrated that dissociation of adipose tissue with collagenase alone or in combination with neutral protease results in efficient extraction of viable and proliferative ASC, and that, post expansion, these cells are capable of multilineage differentiation into adipocytes, chondrocytes, osteocytes, and smooth muscle cells.

Our laboratory conducted a study to compare side-by-side human adipose tissue dissociation to single-cell suspension using crude, non-completely characterized Collagenase I (Worthington Biochemical Corporation) and Liberase MNP-S, a Sterile-A GMP-grade blend of collagenase I and II with a medium content thermolysin component (Roche Diagnostics). Highlights from the study are below…