Determination of the clearance factor for transmissible spongiform encephalopathy agents during the manufacturing process of polygeline.
OBJECTIVE
To determine the safety of polygeline, a gelatine-derived plasma substitute produced from bovine bones, in terms of safety for bovine spongiform encephalopathy (BSE) by evaluating the ability of the manufacturing process of polygeline to eliminate agents related to transmissible spongiform encephalopathy (TSE) through the validation of three main production steps.


METHODS
Laboratory scale experimental process (in duplicate) using 20% hamster-adapted 263K scrapie-infected brain homogenate as infective titrated source (10(9) LD50/2 ml), added to each material before being processed and titrated in hamsters. Experiment 1: time/temperature dependency of gelatine autoclaving. Experiment 2: cross-linking and distillation. Experiment 3: final sterilization. Monitoring period: 1 year with daily animal clinical observation. Histology of all brains.


METHODS
LCG-RBM laboratories, Italy; strict GLP compliance.


RESULTS
Heating the gelatine (at conditions lower than those used in production process) was very effective in inactivating the infectivity of TSE agents. Clearance factors were reproducible, dependent upon time and temperature, reaching a total theoretical process clearance in the range of 9.2-13.8 [6.9 + 2.3 (+ 4.6)] log10 LD50.


CONCLUSIONS
These experimental results provide further important data confirming the safety of the procedural steps; this complements the safety due to the careful sourcing of the raw material. There is high assurance that there is no significant risk of TSE transmission to humans by the therapeutic administration of polygeline.
LCG-RBM, Istituto di Ricerche Biomediche A. Marxer S.p.A., Colleretto Giacosa, Italy.
S
S
Peano
G
G
Reiner
M
M
Carbonatto
L
L
Bodenbender
P
P
Boland
K J
KJ
Abel
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002417:Cattle; D006224:Cricetinae; D004339:Drug Compounding / Q000379:methods; D004340:Drug Contamination; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D005260:Female; D007928:Lethal Dose 50; D008647:Mesocricetus; D010952:Plasma Substitutes; D011097:Polygeline; D012608:Scrapie / Q000635:transmission*; D013242:Sterilization
D010952:Plasma Substitutes; D011097:Polygeline