Improved gene therapy analytics permit monitoring of critical quality attributes and increased manufacturing efficiency

Show Notes:

I began the interview by asking Jonathan if he could describe some of the manufacturing challenges facing the gene therapy industry today. He said that there is currently a capacity crunch for vector manufacturing and a great deal of focus is being spent on where one should manufacture. Once that is established, the question becomes how to manufacture. There are no established template processes for vectors, so process development is more intense compared to more establish manufacturing processes like antibodies, for example. There are also no established packages of analytical technologies, which means that there is usually one development team establishing the process and one development team establishing the analytical characterization. This can create a chicken vs. egg scenario where each team is waiting on the other for test results before they can move forward.

Next I asked him why scale-up of gene therapies is particularly difficult. He explained that the scale-up isn’t inherently more difficult, just less mature. Historically viral vectors have been manufactured using adherent cell lines with transient transfection. This is a difficult process to scale-up. Now there is more production using suspension cell lines, so It is only a matter of time before really scalable production systems are established.

We then discussed how analytics are critically important to biomanufacturing and gene therapy is no exception. Jonathan described analytics currently being used in gene therapy manufacturing to monitor critical quality parameters including dynamic light scattering, analytical ultracentrifugation to PCR, surface plasmon resonance, and electron microscopy. He pointed out that it is important to have these orthogonal techniques to measure different parameters with some degree of overlap. This helps to ensure compete characterization and provides a level of redundancy that’s necessary to for reliable results.

I then asked in more detail about dynamic light scattering and the limitations to this technique. He said that dynamic light scattering (DLS) is a great technique that has broad applicability with very quick results. However it is a low-resolution method that cannot often resolve entities that are similar in size. DLS can detect particles over a very broad size range, but the size of the particles of that we are trying to characterize in gene therapy are often in the lower 1% of that range. This means that the resolution of the particles of interest and smaller contaminants can be very difficult to identify using DLS.

Next I asked Jonathan if he could describe the MiniTEM, how it can improve gene therapy analytics, and how it works. He described the MiniTEM as a compact electron microscope controlled by an integrated software package that automates many steps that microscopists typically need to do manually. The process of analyzing a sample is done in 3 steps. First, you need three microliters of sample, which is fixed on a copper mesh grid. Next the grid is inserted into the microscope and a series of images are taken. This step can be done manually or automated using the built in software. Finally the images are processed using images analysis algorithms that detect and classify the different particle types that are observed in the sample. This way the image data is translated into quantitative data that can be used in analyses, like particle integrity, purity or aggregate analysis.

Next, I asked about a recent infographic, which showed how the MiniTEM could be implemented to reduce development time. I asked Jonathan to explain for listeners how the process is streamlined with MiniTEM. He began by stating that process development is a tough job where scientists are given relatively little time to make key decisions on what methods to use, what conditions to maintain, and what to measure. To make good decisions, scientists need high quality information and they need it almost immediately. The MiniTEM enables this by putting the power of electron microscopy in the process development or analytical lab.

He went on to say that while there are lots of complimentary methods available, the MiniTEM is perhaps the only method that provides real visual confirmation about what is going on in the sample. At Vironova they have seen time and time again that this visual information provides insights that other methods miss. Getting these insights early can save weeks or even months of time and allow informed decisions to be made quickly.

I also asked Jonathan how, based on the information in the infographic, that MiniTEM can increase the number of projects that can be run simultaneously. He said that we often view shortened development time as being critical to getting products to the market faster and this is one important aspect. However, the reality is that process development is one of the main bottlenecks in the development of new therapeutics and process development teams always have more products in the pipeline than they have the capacity for. So, shortening the development cycle for a single project also increases the efficiency of a given team of scientists. Meaning that they can become more productive and develop more projects in the same period of time.

I closed by asking Jonathan if he had anything else to add for listeners. He said that the team at Vironova is immensely proud to be part of the exciting field of cell and gene therapy. It feels really meaningful to see that the therapeutic market is moving from treatment to cures. Vironova believes that their tools and services provide differentiated insights that can be enabling to the success of scientists in process development and analytical labs.

He said that they recently placed MiniTEM systems at the heart of two great gene therapy centers; one in Cambridge, Massachusetts at the Cambridge Innovation Center and the second in London at the Francis Crick Institute. He added that if anyone listening thinks that they can benefit from the insights provided by the MiniTEM, they shouldn’t hesitate to contact Vironova to set up a demonstration.

To learn more about the MiniTEM, please visit

To view the infographic, please see Stop Measuring Things in the Dark

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