Effect of manufacturing process parameters on virus inactivation by dry heat treatment at 80 degrees C in factor VIII.
OBJECTIVE
Dry heat treatment at 80 degrees C for 72 h is used as a virus inactivation step for some coagulation factor concentrates such as Bio Products Laboratory's (BPL) factor VIII 8Y. In the current study, the effect of this process has been tested on a range of viruses. In addition the effect of various manufacturing process parameters on virus inactivation has been investigated.


METHODS
Samples of product intermediate were obtained from manufacturing, spiked with virus and subjected to freeze drying and dry heat treatment. Virus inactivation was determined by infectivity assay.


RESULTS
Freeze drying followed by dry heat treatment was effective for inactivating a wide range of enveloped and nonenveloped viruses. Sucrose or protein concentration had no effect on virus inactivation. Product presentation or the interruption of heat treatment also had no effect. The inactivation of some of the viruses was greater at higher residual water content but under such conditions the stability of the product was reduced.


CONCLUSIONS
This virus inactivation step was effective for a wide range of viruses and over the range of process conditions encountered in manufacturing. This demonstrates the robustness of this process step.
Roberts
P L
PL
Bio Products Laboratory, Elstree, Herts, UK. peter.roberts@bpl.co.uk
Dunkerley
C
C
McAuley
A
A
Winkelman
L
L
D003666:Decontamination / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control; D005169:Factor VIII / Q000302:isolation & purification* / Q000592:standards; D005612:Freeze Drying / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D004364:Pharmaceutical Preparations / Q000302:isolation & purification* / Q000592:standards; D038301:Virus Inactivation
D004364:Pharmaceutical Preparations; D005169:Factor VIII