This is an abridged and edited excerpt. To hear the audio file of Dr. Sasisekharen's entire presentation, please click the Download Now button below this transcript.
To familiarize yourself with Dr. Sasisekharen and his work, click here to access a National Institutes of Health article. For more information on orthogonal analytical techniques being applied to address glycobiological systems, click here to read an article by Dr. Sasisekharan from the journal Nature Methods. To view the PowerPoint on follow-on biologics that Dr. Sasisekharan and colleagues presented to FDA earlier this year, click here.
[Biomolecules] are complex molecules that represent a continuum of technical, regulatory and legislative challenges Technology is available to [define and characterize] them , but the critical issue is to use these technologies effectively, to understand and de-mystify the challenges so that we can manage the risks associated with these molecules. And I also believe that there is an opportunity for science to play a role in shaping the cockpit so that we are able to think of the framework [that will be needed].
Ill focus first on characterization and process-related issues, then on the Critical Path Intiative issues such as mechanism of action and full clinical based aspects using biologicals to get into some of the mechanistic issues that we heard Dr. Woodcock talk about.
Consider the historical view of the globe, and the world as we now know it. Technology brings everything together, which in many ways has brought about globalization and all its challenges. But, enabling this connectivity to happen is the very important message of standardization.
As Dr. Woodcock has said, science, and especially life science has been done, up until now, in a rather hit or miss fashion, without the proper framework, and many of the mechanisms have not been understood. But modern biology is different now.
The old biology was largely a reductionist biology. You had a concept of one gene, one protein, a very important magic bullet target of a reductionist science. And of course, much of that was based on very important technologies relating to sequencing DNA protein....which led to the biotech revolution.
But within the last 5-10 years, and after the human genome sequencing, we have taken a more integrated approach a more systems approach to life sciences. We see that its not the pieces, and how you get a point-to-point comparison, but its how you get things holistically how you apply genomics, proteomics, high-throughput technologies that has really brought a very different framework in terms of looking at the life sciences.
So, youve moved from a hypothesis-driven, reductionist approach to a more integrated way of looking at complexity. That takes us into very interesting dimensions allowing us to view not only the number of components that make up the body but how these components are hierarchically organized, to an integrated approach to structure/function relationships, to get a truly mechanistic understanding of what is going on. In many ways you can look at this as a simple circuit board of how the cell or tissue components come together.
Standardization enables us to come up with a more systematic way of being able to manipulate systems, use a variety of different techniques to measure the manipulation, store this information in databased and use the data to develop models. This is at the heart of how the life sciences are really changing. Not just in the way were thinking about or approaching the problem, but in the way were framing it, so that we have a more integrated way of looking at it If you do not standardize, and make the manipulations and measurements, its sort of like garbage-in, garbage-out.
Genomics is a classical example weve come to realize that standardization will be central to our being able to derive meaningful information from the human genome.
So lets think about problems from the systems approach to address the challenges that we face in hit or miss clinical trials. Regarding characterization of complex molecules, as Dr. Nasr very eloquently said, in order to demystify the black box associated with them, one must leverage cutting-edge technology to achieve characterization of the chemical constituents. You need to look at the relationship between the process and the product to be able to eventually get to the mechanistic underpinnings of function
I think that those two spaces the spaces of characterization and the spaces of mechanism is where there is a gap that we truly need to understand using an integrated approach not only the biology but the chemistry and processes that result in a product.
Unlike with small molecules, the challenge with biopharma is the fact that very often, analytical techniques are used as stand-alone techniques to check the box; in other words, if you use NMR or a mass spec to get a certain measurement, youre looking at that measurement as an individual measurement and not really looking at that measurement in the context of a complex mixture.