RT Journal Article
SR Electronic
T1 Evolution of Endotoxin Contamination during Production of a Therapeutic Serum
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 375
OP 382
VO 61
IS 5
A1 Hugo Massaldi
A1 Víctor Morais
YR 2007
UL http://journal.pda.org/content/61/5/375.abstract
AB A comparative bench-scale study of endotoxin contamination is presented for two common processes of inmunoglobulin purification from equine plasma: ammonium sulphate fractionation of F(abʹ)2 fragments and caprylic acid precipitation of non-IgG proteins. To this end, both processes were carried out under normal sterile conditions, using sanitized material and equipment and optimal water quality in a clean but open environment. Stream samples, taken at different stages from each process, were analyzed for endotoxin content by the Limulus Amebocyte Lysate (LAL) test. It was found that exogenous contamination preferentially came from endotoxins already present in reagents and/or raw materials, whereas contamination from the environment was minimal. Endogenous endotoxin accumulation, concomitant with the concentration of proteins during processing, was found to be an important factor. With classic technology, blood extraction and sterilizing filtration are critical points for both processes. It is concluded that sterility is not a sufficient condition to obtain an endotoxin-free product. Only with proper sanitization of material, and by applying the caprylic acid purification process with a starting plasma below 4 –5 EU/mL, would it be possible to achieve a final product within the norm.