The ICH Q6B guidelines state that for all biopharmaceutical products an assessment needs to be made to determine the presence or absence of any process related impurities and contaminants. These are derived from the manufacturing process and are classified into three major categories:

A downstream process should be designed to remove or minimize process residuals and methods should be developed to allow quantitation of process-related impurities of interest via the analysis of process intermediates, Drug Substance and Drug Product.

BioPharmaSpec provides methods for the analysis of a significant range of impurities. These methods have been developed to allow identification and quantitation to low ppm/ppb limits. Our service includes:

Process-related impurity Examples Method Usual quantitation limit
Inducer Sugars (Arabinose, Isopropyl-β-D-thiogalactopyranoside (IPTG)) GC-MS 100ppb
Cell culture antibiotic Streptomycin
LC-MS/MS 10ppb
Stabilizer Sugars GC-MS 100ppb
Antioxidants (Ascorbic acid) GC-MS 100ppb
Solubilizer Amino acids Derivatization LC fluorescence 1ppm
Surfactants (Tween, Polysorbate, Triton) LC-MS/MS 10ppb
Denaturants (Guanidine, Urea) Derivatization LC fluorescence 1ppm
Buffering capacity Amino acids Derivatization LC fluorescence 1ppm
Tonicity modifier Amino acids Derivatization LC fluorescence 1ppm
Reduced sugars GC-MS 100ppb
Reducing agents Glutathione, DTT etc LC-MS/MS 10ppb
Chelating agents EDTA GC-MS 1ppm
Antifoam agents and processing additives PEG and PPG LC-MS/MS 10ppb
Free PEG in a PEGylated protein product PEG LC-MS/MS 10ppb

BioPharmaSpec has significant experience with these methodologies and is able to develop pre-analysis purifications to reduce interference as and when required. Our scientists can also develop bespoke methods for new/unusual process additives. Please contact us if you would like to know more.