Pegylation of proteins is often used to suppress immunogenicity, prolong the half-life over the native protein and/or increase the solubility of hydrophobic protein drugs. Pegylated proteins present unique challenges to analytical assessment and structural characterization.
BioPharmaSpec scientists have been characterizing pegylated proteins for over three decades and can work with you to devise the best structural and physicochemical characterization strategies for your development plans.
Whether the product of interest is a new product or a biosimilar (e.g. pegylated GCSF), structural and physico-chemical characterization are a crucial part of biopharmaceutical product development. The expectations of the EMA and US FDA, in terms of structural characterization, are outlined in ICH Topic Q6B.
ICH Topic Q6B provides examples of technical approaches which might be considered for structural characterization and confirmation, and evaluation of physicochemical properties of the desired product, drug substance and/or drug product. The guideline recognizes that new analytical technology and modifications to existing technology are continuously being developed and should be utilized when appropriate.
Regulatory guideline documents recommend that the following are assessed:
- Primary (de novo) Amino Acid Sequence
- Amino Acid Composition
- Terminal Amino Acid Sequence
- Peptide Map
- Disulfide Bridges
- Carbohydrate Structure
- Secondary and Tertiary Structure
Product Specific Technical Considerations
Particular attention should be paid to the following structural elements which are important and challenging when analyzing pegylated proteins:
- Site(s) of pegylation and level of occupancy
- Disulfide bridges
- Product- and process-related impurities