From raw materials to intermediates and final products, Avecia’s Analytical Development team provides the essential link between the production of an oligonucleotide, and determining that the product meets all specifications required by our customers. Our team expertly develops, qualifies, and validates analysis methods to ICH guidelines for raw materials, intermediates, adjuvants, and APIs, and has extensive experience managing the particular challenges of oligonucleotide analysis. Our team has developed and validated analytical methods to support product regulatory filings, and can provide Chemistry Manufacturing and Controls (CMC) documentation and support to assist you with the preparation of your regulatory filings worldwide.
Method development activities can begin with one of our generic methods and be tailored to best suit the specific oligo, or we can assist in the transfer of methods directly from our customers or other analytical service providers. For early phase projects, these methods are verified, assessing accuracy, precision, specificity, and other measures for the main peak and impurities. For later phase projects, typically late Phase II or early Phase III, the methods are validated; validation is also generally required before ICH stability testing, and is required before process validation.
Oligonucleotide Sequence Confirmation: Liquid Chromatography combined with Electrospray Ionization Mass Spectrometry (ESI-LC-MS/MS) is utilized to sequence oligonucleotides. Our dedicated state-of-the-art Agilent mass spectrometer equipped with MasHunter software has high resolution, high sensitivity, and an extended dynamic range, well suited for sequencing purposes. Our experienced staff has sequenced both DNA and RNA oligonucleotides of up to 30 bases, typically with 100% coverage. Sequences have included oligonucleotides with conjugated cholesterol, various linkers, modified or restricted bases, and modified sugars. We also have the capability and experience to sequence oligonucleotide mixtures with or without chromatographic separation.
Avecia’s Quality Control team performs environmental monitoring, raw material, in-process, and final product analysis, and stability testing under the ICH Q7 requirements to ensure the integrity of our facility and your products. Most API and intermediate release testing is performed on site, including UPLC and HPLC, LC-MS/MALDI, Thermal Melt (Tm), NMR; any off-site testing is performed only at facilities audited and approved under our quality system.