The Cell Culture Dish Podcast – Providing the latest for the cell culture industry!
Demystifying the FBS Selection Process – A guide for evaluating product quality, origination and cost consideration
In this podcast, we talked with Chris Scanlon, Global Marketing Development Manager at Thermo Fisher Scientific about how to effectively evaluate which FBS product is right for each application. This includes weighing product quality levels and country of origin. Chris also shares strategies for maximizing purchasing options and new FBS products on the horizon.
We began the interview by talking about how FBS has evolved to include several different product quality levels to meet the needs of end users. Chris shared that in the 14 years that he has been working with FBS that there has been an increasing number of tests performed to meet specific application requirements. Twenty to thirty years ago there were far fewer tests conducted, now Gibco sera runs up to 96 tests to give serum a more defined scope.
Next, I asked Chris about serum origination as one way to differentiate serum, how important is it and what does it tell consumers. He explained that there are two areas where origin can be important. The first is with respect to viruses. There are some countries that still have viruses like foot and mouth and blue tongue, for example. So, it can be important to understand the origin.
The other area where origin is important is in regulatory requirements. FBS from certain countries can’t enter other countries due to regulations, thus it is important to be mindful of serum origin and the FBS import requirements for your country.
He went on to describe a recent study that Thermo Fisher Scientific conducted. The study took 18 months to complete and involved over 500 researchers. In the study, they surveyed researchers about the specifications that were most helpful to them in determining what they would purchase. Fifteen specifications came back as most important with the origin being number 12. This was a surprise as they expected origin to be higher on the list. It turned out that endotoxin, hemoglobin, total protein and filtration quality made the top of the list, but origin wasn’t in the top 10.
I thought this study was very interesting and asked Chris what were some of the characteristics of FBS that end users were looking for most. He said that endotoxin was number one as it can really define the quality of serum. Endotoxin is measured at collection and it demonstrates how well the raw serum was collected. For instance, was it collected using a closed system and aseptic techniques. Once you have that endotoxin number, it can’t be changed, so it gives researchers a real look at how carefully collection was conducted. This in turn is an indication of whether the serum was exposed to any other contaminants that would hinder research. As such, endotoxin serves as a real quality marker. In addition to endotoxin, hemoglobin, total protein, osmolarity, pH, and filtration were listed as specifications that help researchers decide what to buy.
Next I asked Chris about Thermo Fisher Scientific’s FBS categories and how they are designed to help researchers find the best product for their needs. He said that they recently changed their categorization from five categories to three. They made the change because with five categories there was too much overlap between product specifications and it was difficult to understand the product differences. The team looked at the entire portfolio and compared this to the responses that they had received in the survey to develop a system that was easier to navigate. The new categories are Value (up to 50 tests), Premium (up to 96 tests), and Specialty where products are delineated for specific applications. It became easy for customers to make decisions between the three based on the culture requirements of cells they were using and their specific application.
I followed up by asking about Specialty FBS and their custom o...
Reducing Fill Risk in Drug Product Manufacture Utilizing New State-of-the-Art Systems and Platforms
In this podcast we talked with DQ Wang, PhD, and Vice President, Formulation, Fill and Finish of WuXi Biologics about their DP4 multi-product fill & finish facility featuring the Vanrx SA25 robotic, gloveless, isolator-based filling system. The system significantly reduces drug product fill risk and provides greater aseptic assurance. The facility is the first in China to use this technology platform and the system fits perfectly with “scale-out” manufacturing paradigms. This highly-flexible platform can easily transition between various Container Closure Systems (CCS) such as vials, pre-filled syringes and cartridges including the new Ready-To-Use (RTU) formats
We began the interview by talking about the completion of pre-filled syringe drug product runs in one of WuXi Biologics’ drug product fill facilities in Wuxi, China. What made these runs so unique is that they were produced in a new state-of-the-art facility that utilizes the Vanrx SA25 system. The system allows WuXi Biologics to greatly reduce risk for each fill and the amount of human intervention compared to traditional automated fill lines. Dr. Wang went on to say that it also allows them to perform fills for the first time using pre-filled syringes. He noted that adding this capability is another huge step towards their goal of building open-access technology platforms with the most comprehensive capabilities and capacities in the global biologics industry.
I followed up by asking DQ how human intervention can be reduced even further than what is already prevalent in the industry with automated fill lines. He explained that this gloveless, isolator-based system performs fully programmable, robotic functions for all aspects of the fill. The fully robotic functions include VHP sterilization of the container closures, liquid dispensing in the CCS of choice using a single flow path, capping, and delivery of the batch. After those steps, the Clean in Place (CIP) function is also programmed into the run. Lastly, there is integrated programmable and robotic air and particle sampling among other in-process checks and an integrated electronic batch record (EBR). All of this is done without human intervention, thereby removing one of the key areas where mistakes can be made during drug product manufacture.
Next I asked about the CCS chosen, pre-filled syringes, and whether the unit was dedicated solely to this type of configuration. He clarified that the unit is highly flexible and that it can handle a wide variety and sizes of CCS, such as vials and cartridges, in addition to pre-filled syringes. Additionally, the unit is able to handle the new simplified, two-component Ready-to-Use (RTU) CCS. These RTU formats reduce in-run risks. By design, the RTU formats reduce rejection rates caused by particles and other part defects that are more common in traditional rubber stopper and aluminum crimp seal configurations. He added that the system is also capable of performing inert gas overlays and for PFS and cartridges offers a servo-driven vacuum plunger design for bubble-free fills. Thus, the system is very adaptable to a wide-range of CCS types.
We transitioned the discussion to the primary drivers behind their decision to implement the Vanrx SA25 system in this new DP facility. DQ explained that their focus is always on patient safety and there are many reasons why the system is ideal from that perspective. There were other time and economic drivers as well. WuXi Biologics’ manufacturing goal is to quickly and safely advance their customers’ remarkable therapies to market. They knew that through this systems’ modular design and installation ease that it would accelerate the process of adding DP filling capacity, especially when compared to conventional filling systems. The qualification and validation of the process also takes less time due to the design pro
The Challenge of Staying Current with Regulatory Changes – How one company is providing a solution
In this podcast, we talked with Ken Chen, MBA, Senior Director, Regulatory Affairs, WuXi Biologics about staying current with regulatory changes. We discussed how WuXi Biologics recently began publishing a quarterly summary of regulatory updates on new or revised guidance documents from the various global regulatory agencies and how this is a valuable resource for anyone in the biological drug development arena.
I began the article by asking Ken what prompted WuXi Biologics to begin publishing these regulatory updates. Ken explained that WuXi Biologics works with companies from around the globe in all facets of product discovery, development and GMP manufacturing and across the full drug development continuum from preclinical to commercialization. Due to the nature of the services they provide, they need to provide an optimal regulatory CMC strategy and thus remain up-to-date with the relevant global regulatory expectations. They work proactively to minimize regulatory risks by identifying regulatory changes or new hurdles in advance and thus if needed they can rapidly perform gap analysis and formulate a strong risk mitigation strategy.
We then discussed how having these updates provides a win-win for both WuXi Biologics and their clients. Ken described how the companies that are working with WuXi Biologics are filing INDs and BLAs in various jurisdictions and WuXi Biologics must provide results and documentation that will be a part of those filings. Hence, WuXi Biologics must adhere to the quality and GMP standards required in those various geographic venues. He went on to say that since they are such a large organization and because they provide a one-stop, single-source development platform it was imperative that they develop an internal mechanism to keep their entire staff up-to-date with the relevant, wide ranging and rapidly evolving regulatory updates and expectations.
I asked Ken about other resources available with regulatory updates. He said that there are other resources available and that they use some of these to help put their update together, but many are not organized by agency and topic. In addition, most and are not as wide-ranging, from a global perspective, as what they felt like they needed for their team. They decided that a quarterly update was just the right size for teams to digest and, if necessary, act on to stay current without disrupting normal daily operations. They thought that offering the translations of relevant NMPA updates and documents would be unique to current industry resources.
Next I asked Ken about whether the updates were just for the regions in which WuXi Biologics has operations – China, Europe and the United States. He clarified that they work with clients to file INDs in many countries around the world not just in the U.S., China and countries currently and formerly governed by the European Medicines Agency or EMA. Some of those other countries include Australia, Korea, Singapore and Japan, thus their updates need to include the regulatory requirements from those countries as well. They also review updates coming from Health Canada, ICH, WHO and PICs amongst others if relevant to biological therapeutics and vaccine development.
I was curious about why they decided to make these updates available to the greater industry. Ken explained that many of the leaders at WuXi Biologics came from drug development companies both large and small from around the globe and they wished that they would have had a similar consolidated and comprehensive update. Ken said that although many larger companies have similar teams assembling this information, many smaller companies do not have the same resources. WuXi Biologics thought that their update would be valuable for them, especially for companies wishing to file in multiple jurisdictions. They also provide a translated update of the
Solving the challenges of standardizing cell counting to ensure reproducibility in experiments, assays and manufacturing processes
Cell counting is a challenging technique, with many pitfalls, that can delay entire projects. We talk with Christian Berg about how new technologies are solving these challenges and enabling standardization of cell counting across organizations.
A Look Towards the Future of 3D Cell Culture – A panel discussion
Spheroids can be an improved model for cancer in the lab compared to standard 2D cell culture. When cancer cells are cultured as spheroids, they are able to maintain the shape, polarity, genotype, and heterogeneity observed in vivo (1). This allows researchers to create models that are much more reflective of what’s going on in the body. For a simple example, if you think about drug penetration into a 2D monolayer of cells it’s completely different from drug penetration into a solid tumor. In a 2D monolayer each cell is exposed to the same concentration of drug whereas in a spheroid, like a solid tumor, there are gradients of drug exposure.
More and more we’re seeing researchers move away from cancer cell lines and move more toward specialized cancer models such as patient derived models. The hope here is to find the appropriate therapies for each individual patient.
Computer Aided Biology Platform Helps Companies Meet the Challenges of 21st Century Biomanufacturing
In this podcast, we interviewed Markus Gershater, Chief Scientific Officer with Synthace about computer aided biology and how it addresses several common biomanufacturing challenges. We also discussed ways to build a common culture between science and software.
I began the inteview by asking Mr. Gershater to describe the concept of Bioprocessing 4.0 and what it means to the industry. Markus explained that the term 4.0 refers to the industrial revolutions that have happened throughout history. The first began when steam was introduced as a power source, next came electrification and the production line. 3.0 refers to the incorporation of automation and 4.0 is the connection of different devices and automation through digital technology. This involves cloud computing that enables data storage, computing and analysis. This is particularly important in a complex industry like bioprocessing that requires sophisticated knowledge and control. Bioprocessing 4.0 will enable the industry to progress to the next level.
Next I asked Markus to explain the solutions that Synthace provides in this area. He described how Synthace started as a bioprocessing company that was looking for a way to conduct more sophisticated, automated experiments. The result was the creation of their software Antha, which can auto generate instructions for biological protocols. This means that scientists can specify the protocol they want to run and Antha will works out all the details down to the every step of the run. It then converts those detailed actions into scripts for each automated device to run the protocol. The user hits go and the robot will run the specified protocol with the instructions that Antha generated. This automatic generation of scripts makes automation more user friendly and powerful. In particular, there is a problem with lab automation due to the complexity of programing it. Antha is able to make complex lab automation implementable.
Markus goes on to say that the beneficial knock on effect is digital integration. The devices used in protocol automation are only a small part; there are also analytical devices that produce data. What is needed is a way of structuring data from all of these diverse pieces of equipment. Since Antha generates all the detailed instructions that go on into a particular protocol, it also has the detailed structure of the experiments. So at the end of any chain of actions, Antha can provide the provenance of all data points. Thus, it can also auto structure data into the context of experimental design.
As the industry runs more complex and high throughput experiments, the bottleneck shifts to data structuring. Antha has become a tool that allows the automation of lab processes as well as the data processing from those lab processes. This permits dynamic updating as the structure of the experiment updates.
We then discussed the technology behind the product. Markus explained that first step in getting started is to identify a specific protocol. Then, for example, Antha specifies samples that need to be diluted and provides a framework with specific parameters. Next, you need to look conceptually at how you can move liquids around to fulfill this design. What equipment do you need to run and what consumables? Once you have those, Antha can generate the lower level tedious details. This allows users to change one detail of the experiment and Antha will calculate a new set of instructions. Antha can then pass these specific instructions to devices through the Antha hub, which communicates with the equipment. Once users are satisfied that the equipment has been set up properly then they can hit go and the experiment will run.
I asked if there were any case studies that could be shared to show how this would work in a real life setting. He described how their case studies range from programming relatively sim