Residuals from lysis processes

When mammalian red cell Hb is used as the raw material for production of a modified Hb, the requirement for the minimization of plasma proteins and red cell stroma is a rigorous and general one. Some manufacturers meet this requirement by extensive red cell washing to reduce contamination by residual plasma, controlled lysis, and careful filtration of the hemoly-sate, followed by ultrafiltration. Other manufacturers add a chromatographic purification step to this procedure. Published data indicate that the phospholipid content of the so-called stroma-free Hb resulting from either process is very low (<2pg/ml). ... 

Host-cell DNA is an upstream-derived process-related impurity in drug substances derived from a cell culture process, often the result of cell lysis, or rupture resulting from physical exertion (e.g., shear forces, excessive air bubbling, etc.) in a culture vat or cell pelleting or removal during harvest. The guidelines outlined by the WHO surest that up to 10 ng of residual host-cell DNA per purified dose is considered acceptable. It has been suggested that whenever possible, the level is no more than 100 pg of cellular DNA per dose. 

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