Impurities in Biologics

Antifoam agents, divalent metal cations and EDTA impurities are often associated with the manufacturing and formulation process of biologics. Maxxam has developed a number of analytical procedures required for in-process monitoring as well as bulk and final product release testing. We specialize in validation of analytical methods involving many complex matrices associated with bio-pharmaceutical product development.

Process-related Impurities
Process impurities can be introduced into a final product by:

  • Impurities in process reagents or formulation excipients
  • Inefficient removal of intermediate process components (e.g. Palladium catalysts)
  • Chemical breakdown of ingredients (e.g. peroxides)

These can have negative effects on both process materials and final products. Aside from the potential toxicological properties, in biologics there is the added possibility of unwanted species altering the active’s 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.
Contaminants investigated by Maxxam:

  • Silicone
  • Antifoams
  • EDTA
  • Trace metals (W, Fe, Zn, Al)
  • Phthalates

Challenging matrices routinely analyzed by Maxxam:

  • Guanidine HCl
  • Tween 80
  • Mineral oils
  • Fermentation broth
  • Culture media

Notable Impurities
Ethylenediaminetetraacetic Acid (EDTA)
EDTA is a common chelating agent used in the bio-processing industry for removal of divalent metal ions. Maxxam’s analytical methods utilize HPLC and LC-ICPMS for quantifying this analyte over a wide concentration range (low ng/ml to high μg/ml) in intermediates and final products.

Trace Elemental Impurities
Maxxam offers heavy and other trace metals analysis in pharmaceutical drug products and dietary supplements of various types ranging from proteins and cytotoxic compounds to peptides and oligomers. Our heavy metals analysis service falls fully in line with the new USP Heavy Metals general chapters.

Silicone
Silicone is found in antifoaming agents (used in fermentation) as well as in siliconized syringes. Since inorganic silica is the most abundant mineral in the earth’s crust, measuring trace levels of silicon is extremely complicated. Selective detection of silicone in materials contacting a silica substrate such as glass is even more complex. Maxxam has developed accurate, selective and sensitive procedures for quantifying levels of silicone in pre-filled syringes, cell culture media and bulk products or intermediates.