Impurities in Biologics
Antifoam agents, divalent metal cations and EDTA (ethylenediaminetetraacetic acid) impurities are often associated with the manufacturing and formulation process of biologics. Bureau Veritas has developed analytical methods for in-process monitoring, bulk product and final product release testing. We have expertise in validation of analytical methods involving many complex matrices associated with bio-pharmaceutical product development, including culture media, mineral oil and Tween 80.
Process impurities may be introduced into a final product through:
- Impurities found in process reagents or formulation excipients
- Incomplete removal of intermediate process components (e.g. palladium catalysts)
- Chemical breakdown products of ingredients (e.g. peroxides)
Aside from the potential toxicological properties, in biologics there is the added possibility of unwanted species altering the Active Pharmaceutical Ingredient's (API) structure and physico-chemical properties (e.g. aggregation). While there are many reasons for screening pharmaceutical products for impurities, immunogenicity is a major concern for biological therapeutics. Bureau Veritas is experienced with evaluating contaminants including:
- Antifoam - includes compounds and emulsions used as APIs, excipients and process aids in pharmaceutical applications. They require foam suppression, such as fermentation, maceration, percolation and mixing. Bureau Veritas has developed sensitive methods to test and quantify residual antifoam compounds in the manufacturing and formulation of pharmaceutical products.
- EDTA - a common chelating agent used in the bio-processing industry for removal of divalent metal ions. Bureau Veritas’ analytical methods utilize HPLC for quantifying EDTA over a wide concentration range (from low ng/ml to high μg/ml) in both intermediates and final products.
- Phthalates - includes plasticizers and solvents used in some personal care and consumer products, plastic containers/packaging and as excipients for controlled time-release capsules and coatings in pharmaceuticals. This class of chemicals is identified as having possible toxic effects to human health and the environment due to endocrine disruption activity. As such, phthalates have been identified as chemicals of regulatory interest by the EPA, Health Canada and the European Union. Bureau Veritas has validated methods for analyzing and measuring phthalates present or leached from a variety of materials.
- Silicone - found in antifoaming agents that are used in fermentation and in siliconized syringes. Since inorganic silica is the most abundant mineral in the earth’s crust, measuring trace levels of silicone is extremely complicated. Selective detection of silicone in materials contacting a silica substrate such as glass is even more complex. Bureau Veritas has developed accurate, selective and sensitive procedures for quantifying levels of silicone in pre-filled syringes, cell culture media and bulk products or intermediates.
- Trace metals impurities - we offer sensitive analysis of heavy and other trace metals in pharmaceutical drug products of various types ranging from proteins and cytotoxic compounds to peptides and oligomers. Bureau Veritas’ metals analysis meets the requirements of USP Elemental Impurities general chapters.