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about the Event
The “USP Workshop on Therapeutics Peptides and Oligonucleotides: Regulations and Quality Standards” is based on the success of previous workshops and input from attendees. This USP workshop will continue to inform public standard setting for therapeutic peptides and oligonucleotides by gathering experts from the analytical, process development and regulatory communities to share best practices and success stories. Both of these product classes are rapidly growing, with novel modifications and formulations for virtually every therapeutic area presenting new challenges. Therefore, best practices and guidance are critically needed to expedite quality products coming to the global market.
Panel discussions and networking events will provide opportunities for audience members to engage with the speakers and USP staff on challenges that they face and potential areas to develop new guidelines and standards.
Risk assessment for a nitrosamine contamination of peptide APIs manufactured by solid-phase peptide synthesis (SPPS)
Due to findings of nitrosamines in multiple medicines since July 2018, both the FDA and the EMA published guiding documents to all Marketing Authorization Holders requiring them to evaluate their synthetic manufacturing processes for the potential presence of nitrosamines. Both agencies instructed the applicants to utilize the principles described in the ICH M7 and ICH Q9 guidelines for toxicology and risk assessments. Where the assessment identifies a risk for nitrosamine, products must be tested and the risk should be mitigated. This may include a change of the manufacturing process and/or the implementation of a respective control strategy.
These guidances also apply to synthetic peptides. While Bachem assesses both process types, Solid Phase Peptide Synthesis (SPPS) and Liquid Phase Peptide Synthesis (LPPS), this presentation will focus on the risk assessment for the more frequently applied SPPS.
General risk factors will be explained and their assessment for Bachem’s SPPS-related raw materials and processes will be presented. In preparation for potential testing, a quantification method for the nitrosamine structures of concern was developed and validated. The method is based on Head Space Gas Chromatography with MS detection. Based on the assessments we conclude that the risk for a nitrosamine contamination in SPPS peptides can be kept negligibly low.
Vice President of CMC Development, Bachem Americas, Inc.
Matteo joined Bachem in 2004 as Director of Research. During his career at Bachem Americas he covered both the position of VP of R&D responsible for process development, and VP of Manufacturing responsible for commercial production. In his current position as VP of CMC Development, he supports Bachem customers in identifying the activities assuring a successful CMC development. Matteo holds a Doctorate in Chemistry and Pharmaceutical Technology from University of Milano, School of Pharmacy.
Novel approaches in MS characterization of highly modified synthetic RNA
Over the last years, the demand of MS based structural characterization approaches in quality control of oligonucleotide based pharmaceuticals increased notably. Sense strand RNAs with >30 nucleotide building blocks and labile modifications such as N-acetylgalactosamine residues represent thereby a special challenge. We will present direct, robust and easy to use techniques for full nucleotide sequence characterization of highly modified single-stranded RNAs by top down tandem mass spectrometry. This will include a case study for an N-acetylgalactosamine modified RNA sense strand.
The approach can be applied on single strand level, as well as on siRNA duplex level in a single ESI-MS experiment. Based on this technique, we also developed an efficient and highly sophisticated LC-MS(/MS) workflow for the characterization of product-related impurities in oligonucleotides such as methylation as well as PS-PO and rC/rU substitution. This approach allows us to confidently predict the modification sites in oligonucleotide impurities to support process development with important structural information.
Project Chemist QC, Bachem AG.
Giovanni joined Bachem in Bubendorf (Switzerland) in September 2020 as an expert in mass spectrometry of oligonucleotides. In his current position as a project chemist he is responsible for establishing routine workflows for characterization of oligonucleotides and peptides by ultra-high resolution mass spectrometry. Giovanni holds a Ph.D. in chemistry with focus on biomolecular mass spectrometry at the University of Innsbruck, Austria.