Post-translational modification characterisation for protein purity and identity confirmation through mass spectrometry and chromatographic analysis
Post-translationally modified (PTM) forms of proteins are common to drug substances produced by bioprocessing. Also known as variants, these PTM forms exhibit some degree of structural heterogeneity and are produced by the post-translational addition of a functional group covalently bonded to the protein, proteolytics cleavage or degrdation. PTMs can influence the structure, stability, function and how the protein interacts.
Determining post-translational modifications such as misfolding, phosphorylation, oxidation of methionine, deamidation of asparagine and glutamine, variation in glycosylation, and proteolysis can be challenging. A complex array of detailed analytics is required in order to confirm protein identity, ensure a consistent manufacturing process and product quality. Furthermore, an incorrect modification or aggregation can lead to a potentially harmful immune response in the patient or lower product efficacy.
As an post-translational modifications analysis service provider, we apply our knowledge of anticipated PTM and potential PTMs based on your product’s specific structural characteristics to design strategic analytical programs that meet the requirements of regulatory expectations and industry guidance such as ICH Q6B.
We apply the intelligent application of enzyme or chemical digestion coupled with highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) and a range of chromatographic techniques to detect and identify a range of PTMs with comparision against using against an appropriate reference standard as necessary.
Our post-translational modification experts apply a strategic approach to PTM analysis in early development phases to help you to establish product acceptance criteria for ongoing requirements or to support your process validation activities. We employ PTM analysis as part of in-depth structural characterisation studies and as a vital component of comparability programs, stability studies or quality control testing.
Post-translational modifications analysis services include studies to identify or confirm:
• Mis-matched S-S bridges
• N/C-terminal modifications e.g. C-terminal amidation
Comprehensive protein characterisation from one source
With considerable expertise in the detailed analytics required to determine post-translational modifications we provide experienced service to get you the data you need relevant to your development stage but always with an eye on your needs for later-phase development and CMC requirements such as stability testing, regulatory submissions and ongoing analysis. Bringing quality and safety to life, we offer Total Quality Assurance expertise to help you to meet and exceed quality, safety and regulatory standards.
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