Biopharmaceutical Process

1. Biopharmaceutical Process Biopharmaceutical products are synthesized by living cells, and hence during the purification process the substrates for growth, host cell components and product variants must be removed. These impurities include: • Product-related impurities: variants that differ from the desired product; • Process-related impurities: materials added to the process and cellular components.   Product characterization methods in the biopharmaceutical sector have seen considerable advances in recent years, particularly with the development of high-resolution-MS approaches, for example in our ability to investigate glycosylation of antibodies. The need for advanced characterization is also being driven by the biosimilars market where a company developing a generic product must show to the regulators comparability to the innovator product. Profacgen offers a wide range of pharmaceutical services which includes biopharmaceutical product related impurities analysis. A variety of compounds added during the manufacture process of your biopharmaceutical products can appear in the final product as process- and product- related impurities. We provide you with effective process related impurities analysis, and product related impurity testing in biopharmaceuticals. As a result, we can help you to confirm the efficient removal of impurities by the downstream process and absence from the final product. We offer the following technologies for process-related impurities analysis, residual impurity testing and residual analysis in biopharmaceuticals: Product Related Impurity Method Description Host cell proteins (HCP) Commercial kit or customized assay N-terminal truncations N-terminal sequencing Host cell DNA PCR Peptide mapping LC-MS or LC-MS/MS, IsoQuant HPLC Oxidation/deamidation (PTMs) Ion exchange HPLC, cIEF, sialic acid analysis Isoform analysis Disulfide bridge scrambling (mis-folding); conformational impurities Peptide mapping LC-MS or LC-MS/MS, Ellman’s free sulfhydryl, intrinsic tryptophan fiuorescence, ANS dye binding, NMR C-terminal integrity Peptide mapping LC-MS or LC-MS/MS

2. Analytical ultracentrifugation (AUC), SEC/SEC-MALLS, dynamic light scattering (DLS) Aggregation Process Related Impurities Method Description IPTG HPLC with ELSD/CAD PEI HPLC with ELSD/Fluorescence Kanamycin HPLC with UV/Vis Anti-foam HPLC with ELSD/CAD TFA/Acetate HPLC with UV/Vis Cyanate HPLC with Conductivity/ECD Imidazole HPLC with Fluorescence Triton X-100 HPLC with ELSD/CAD Polysorbate (tween) 20/80 HPLC with ELSD/CAD Zwittergent HPLC with ELSD/CAD Pluronic HPLC with ELSD/CAD Protein A ELISA PEG HPLC with ELSD/CAD TRIS HPLC Growth Factors (e.g., insulin, interferon) ELISA With the vast base of isolation techniques and characterization technologies in our GLP / GMP compliant protein analysis laboratories, underpinned by over 20 years of experience in supporting biologic drug development and bioprocessing, we offer a full spectrum of ready-to-use analytical methods for the detection and quantification of process- and product-related residuals and impurities. Profacgen can ensure that you meet all regulatory expectations and specifications for your drug substance and drug product.