Automatizing the Qualitative and Quantitative Analysis of Complex Drugs Using NMR

The life-saving anticoagulant heparin belongs to a category of drugs referred to as “biologics.” Heparin is one of the world’s most commonly sold biologics and is included in the World Health Organization’s “Essential Drugs List.” Biologics are important drugs that are made in cells or extracted from living organisms and used to treat serious chronic illnesses, including cancer, autoimmune disorders, hepatitis and diabetes. Stringent quality control of these drugs during the production process is critical. However, determining their quality is more complex than with traditional small molecule pharmaceuticals. A biologic often contains a mixture of related molecules and composition can vary between the different batches produced. Product quality assessment therefore requires highly informative analytical approaches to validate that a product meets the required specifications.

This webinar will introduce a technique called 2D heteronuclear single quantum coherence (HSQC) NMR spectroscopy for assessing the quality control of heparin. Currently, this is achieved using 1D NMR spectroscopy, following the indication of international pharmacopoeia. However, although 1D spectra can help to confirm the chemical structures of heparin products, it cannot readily identify variability in its composition between batches, which can occur due to differences in the purification methods used and the extraction source selected. The 2D HSQC NMR spectroscopy method, on the other hand, can be used to detect this variability. Once established, the method was automated to take advantage of NMR’s inherent reproducibility and reduce operator to operator variations and prepare for method validation of this quality control approach.

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Key Topics

Using heparin as an example, implementation of the 2D HSQC NMR approach will be described, with a focus on the key parameters and evaluation of sources of variability inherent to the technique. Attention to factors influencing limit of detection, linearity, accuracy and precision are necessary in the development of a robust method for a given material. Another important topic will be how the method can be automated to take advantage of NMR’s inherent reproducibility, reduce operator-to-operator variations and prepare for method validation of this quality control approach. The idea is to develop a method that can not only be used in specialized NMR labs designed to work with this type of drug, but also in the routine control of heparin production and batch release by different pharmaceutical companies. The method was automated using tools in Assure NMR software for qualitative assessment of porcine verses bovine heparin and quantitative analysis of heparins and impurities. The instrument operational performance was also automated to assist with GxP compliance.

Who Should Attend?

The webinar will be of interest to the following individuals:

Quality managers, scientists and technicians who are responsible for the quality control of pharmaceuticals and/or biologics
Users of qNMR
Students considering careers in analytical chemistry and quality assurance

Speakers

Dr. Marco Guerrini

Vice Director G. Ronzoni Institute for Chemical and Biochemical Research Milan Italy. His main field of expertise is the structural activity correlation of carbohydrates using NMR spectroscopy. He contributed to the development of advanced analytical approaches for the characterization of glycosaminoglycans, particularly heparin and low molecular weight heparin.

Dr. Kimberly L. Colson

Business Development Manager Bruker BioSpin Billerica Massachusetts United States

Dr. Kimberly L.Colson began her scientific career in chemistry with a BA degree from Mount Holyoke College. She then received her PhD in Organic Chemistry from The Penn State University while studying structure elucidation of natural products and molecular dynamics using NMR spectroscopy. With a postdoctoral appointment at Yale University in the Pharmacology department Kim began applying NMR to pharmaceutical applications. She then joined the pharmaceutical industry as a NMR spectroscopist at Bristol Myers Squibb and Burroughs Wellcome where she studied complex natural products, proteins and mechanism of action of natural products. To further expand her knowledge she spent a short time as NMR Facility Director at North Carolina State University and then joined Bruker BioSpin where she has been for the past 20 years. Her roles at Bruker have included NMR applications, business development, and product management. She is product manager for AssureNMR, a NMR software tool for automated quality control analysis. Her focus areas currently include quality control, natural products, metabolomics and biologics.