A total organic carbon analysis method for validating cleaning between products in biopharmaceutical manufacturing.
The validation of cleaning procedures for biopharmaceutical products produced by recombinant DNA (rDNA) technology presents a diverse analytical challenge. This is because of the need for quantitation of a broad range of potential residual cellular components, including proteins, carbohydrates, and nucleic acids, as well as trace levels of detergents at various manufacturing stages. The validation of a Total Organic Carbon (TOC) analysis method for use in cleaning validation studies is presented. The method has a limit of detection of approximately 0.1 ppm, with a limit of quantitation of 0.5 ppm. TOC analysis has an accuracy of 50 to 70% or better in the 0.5- to 10-ppm range and demonstrates an overall variability of approximately 5%. The method is broadly applicable to a variety of impurities and contaminants that are likely to be encountered following the manufacture of rDNA products.
Baffi
R
R
Genentech, Inc., South San Francisco, California.
Dolch
G
G
Garnick
R
R
Huang
Y F
YF
Mar
B
B
Matsuhiro
D
D
Niepelt
B
B
Parra
C
C
Stephan
M
M
D001207:Asepsis / Q000592:standards*; D001688:Biological Products / Q000592:standards*; D002244:Carbon / Q000032:analysis; D004274:DNA, Recombinant; D012710:Serum Albumin, Bovine / Q000032:analysis; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000592:standards*
D001688:Biological Products; D004274:DNA, Recombinant; D012710:Serum Albumin, Bovine; D002244:Carbon