Christoph, could you give us a potted history of Site Management Analytics?
So in some ways, the history of Site Management Analytics goes back to the beginning of Merck’s 350 years in business! Back then, Merck guaranteed customers that purchased chemicals were subject to quality control for the first time. Of course, it would be virtually impossible to list all the changes and milestones since then – but it’s been a road of continual improvement and innovation, founded in quality. In my 18 years at Merck, the role of Site Management Analytics has moved away from routine quality control towards more closely supporting our research and development teams with advanced – and still high quality – analytical capabilities. Today, analytics is an integral part of R&D at Merck; indeed, the border between the two is much less defined than it was even 10 years ago. Today, we do remember our roots with some specialized quality control – for example, when less common techniques, such as NMR or X-ray diffraction, are needed. Merck’s business units – performance materials, life sciences and healthcare – are all subject to different regulations as the sectors deal with different products ranging from, for example, liquid crystals for displays to pharmaceutics, so they all have their own respective quality management system. On the other hand, the business is driven by a stronger need for analytics for R&D, which has led Site Management Analytics to focus on R&D activities. The shift has also been driven by trends in miniaturization and automation. To give an example; as you bring a small molecule candidate through clinical development, you need to gain information for crystal form selection, so we do a significant amount of solid-state characterization work. Fifteen years ago, you’d perform different crystallization experiments under different conditions at perhaps a 5 g scale and then send samples to our lab for analysis. Today, the same task is done at a much smaller scale – more like 10 mg and using much more experiments. From these, we gain much more information about the behavior of a compound. The crystallization experiments and analysis of such a higher number of samples are conducted in the same laboratory to maximize efficiency and leverage automation.
How does Site Management Analytics help its internal customers?
Our work spans three core areas across Merck R&D – routine analytical support, project support and innovation, with the latter two taking on the prominent role in recent years. When it comes to routine support, we’re responsible for making relatively simple measurements, but we use sophisticated tools, such as NMR. Here, turnaround times, cost and quality are the three drivers. In project work, we will be tasked with solving more complex problems, which not only involves closer collaboration with our customer – the R&D team – but also other laboratories across Site Management Analytics. As an example, selecting the right crystal form of an active pharmaceutical ingredient is key when entering clinical development. Therefore, many labs doing crystallization experiments and characterizing the crystals using a broad range of analytical techniques, such as X-ray diffraction, differential scanning calorimetry, thermogravimetry, dynamic vapor sorption, measuring solubility and dissolution rate, particle size and shape, nuclear magnetic resonance, infra-red, Raman, and mass-spec, are brought together. The work is done in Site-Management Analytics involving a team of medicinal chemists, people from drug metabolism and pharmacokinetics, process development, regulatory affairs and pharmaceutical development. The answer we deliver is which crystal form should move into clinical development based on scientific consideration. Finally, by “innovation” we really mean technology scouting and the need to consider what our customers may request or need in the years ahead. In other words, to ensure that our R&D continues to exist at the forefront, our analytical support must also be at the cutting edge. And so over the years, we’ve needed to add capability to support work in emerging areas – proteomics, crystal design, gene editing, for example. I have to say that, when it comes to analytical science, remaining competitive means building, developing and maintaining an external network; going to conferences, reading journals, making contact with external biotech companies, CROs, and universities are all key to us offering the best analytical support possible for Merck. It matters that we are an integral part of the scientific society.
Saskia, how would you describe Site Management Analytics?
I’d probably describe us as an internal specialist CRO. We have about 230 people, including 30 PhDs and 40 engineers, with vast expertise in every aspect of analytical science, including chromatography, mass spectrometry, spectroscopy, and microscopy… everything you can imagine! We use that knowledge to support all three of Merck’s business units – life sciences, performance materials and healthcare. We are located in the headquarters in Darmstadt, but we act globally.Could you share an example project from your lab?
Over the last 10 years, there has been growing concern about extractables and leachables (E&L) in the pharma field, and we’ve been involved in a number of development projects on primary packaging or process materials. I’d like to highlight one special project in my laboratory, which I think is not only of interest for Merck’s business, but also for other pharma businesses. Merck Life Science is a global player in providing single-use systems and has a catalogue of more than 400 consumables. Recognizing the importance of E&L, Merck launched the Emprove® program for consumables. The program collects data on the nature and concentration of extractables, in turn, helping customers with risk assessment and process design. Essentially, alongside our portfolio of single-use technologies, we offer comprehensive E&L reports, making Merck’s offerings unique. Now that we’ve laid the groundwork in providing this information, our customers can save time and money, because they no longer need to perform their own E&L studies. What is the origin of the report? Well, you can probably guess that all data are generated by our experts in Site Management Analytics!Can you offer an overview of frequently used analytical techniques?
We rely heavily on chromatography-mass spectrometry – both normal and headspace GC-MS as well as LC-MS. Both are essential for the separation and identification of inorganic extractables and the different techniques are used to cover volatile, semi-volatile and non-volatile compounds. But because of the nature of the challenge in E&L work, we have to use a number of other techniques to cover all possible entities like ion chromatography for anions and ICP-MS for elemental impurities. Invariably, more sophisticated technologies are required for the complex task of structure elucidation – which is also the most time consuming part of a project! The nature of the material also has a significant impact on the techniques required and the complexity of the task. For example, if you do an extraction of a Teflon material, the extracts will be very clean; you may only have one or two peaks to identify and quantify. But if you extract a rubber stopper? You’ll get more than 50 peaks – and I’m sure you can imagine how much more time is needed…What other challenges do you encounter in this deep analytical work?
Sample preparation is typically challenging because we have to keep the scope as wide as possible, as we do not always know what we should find in the extract. Any sample preparation task we perform can have a possible effect on the substances that are included in the extract. Moreover, we can’t easily perform recovery studies because we do not know which compounds are included – and so we try to keep sample preparation to a minimum to reduce any losses of compounds of interest that may occur. Some of the compounds we are looking for require high sensitivity, which can be another challenge, demanding the best methods and instrumentation. Finally, as guidelines for extractables testing are somewhat in development, we have to set the bar as high as we can. And that’s why I’m proud of the Emprove® program – the results of which I hope will contribute to an improved regulatory landscape in some way.What are the most rewarding aspects of your role?
The most rewarding aspect for me is knowing that I contribute to safer products for our customers – and, in turn, safer end products for their customers. I think that will always give me a good feeling! It’s also very rewarding to see how much our group has grown over the years – and how much our work is appreciated.www.SigmaAldrich.com/feel-better
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