Process equipment cleaning verification is required for Good Manufacturing Procedure (“GMP”) compliance and such compliance is intended to ensure that therapeutic products meet the quality and purity characteristics that they purport, or are represented, to possess. As part of GMP compliance, the Total Organic Carbon (“TOC”) assay has traditionally been used to verify the effectiveness of cleaning procedures for the removal of biotechnology product residuals. The TOC assay can be employed between individual production runs as well as when production sites are switched between distinct products. However, an important limitation of the TOC assay is that the detection limit, <0.1 ppm, may be unsuitable for monitoring product carry over and/or cleaning verification for very low dose products, such as certain antibody therapeutics, whose maximum allowable carry over limit is below the TOC detection limit.
In addition to issues concerning compliance with very low dose products, the International Conference On Harmonization Of Technical Requirements For Registration Of Pharmaceuticals For Human Use (“ICH”) document ICH Q7A, adopted by the U.S. Food and Drug Administration in 2001, as well as Health Canada Guide-0028, both recommend the development of active pharmaceutical ingredient (“API”)-specific assays for monitoring product carry over and/or cleaning verification. As the TOC assay is not API-specific, but rather measures total organic carbon regardless of the source, it does not comply with such recommendations.
In light of the inherent limitations to the TOC assay, a more sensitive, and API-specific, assay would be desirable as an alternative or supplementary method to detect biotechnology product residuals when monitoring product carry over and/or for cleaning verification. The instant invention meets that need by introducing a general analytical assay to detect trace amounts of nucleic acid or protein residuals, including monoclonal antibody residuals, which can be used for monitoring product carry over and/or for cleaning verification.
USPTO Backgrounds
USPTO Backgrounds