Temperature Sensitivity within the Pasteurization Temperature Range of Prekallikrein Activator in Stable Plasma Protein Solution (SPPS)

Abstract

Human plasma protein fraction, used worldwide as a plasma expander, produces in some recipients adverse reactions resembling those following infusion of bradykinin. The presence of excessive quantities of a Hageman factor degradation product (prekallikrein activator, PKA) in the protein solution is thought to be the reason for these reactions. Like other manufacturers, CSL has experienced batch‐to‐batch variability in the PKA levels in its plasma protein product (SPPS). In this paper, data is presented showing that PKA is inactivated to a greater extent at the high extreme (60.5 C) of the pasteurization temperature range than at the low extreme (59.5 C). This difference in pasteurization temperature can lead to a two‐ or threefold difference in PKA concentration in the final product and can make the difference between the product being potentially reactive or innocuous, as well as accounting for some of the batch‐to‐batch variability observed in the past.

Технологические Особенности Обеспечения Специфической Безопасности Препаратов Иммуноглобулинов И Альбумина Человека

“…Ïðè èñïîëüçîâàíèè òðàäèöèîííîé òåõíîëîãèè ôðàêöèîíèðîâàíèÿ ïî Êîíó âîçìîaeíî ñíèaeåíèå ñîäåðaeàíèÿ àêòèâàòîðà ïðåêàëëèêðåèíà çà ñ÷åò ïðîöåäóðû ïàñòåðèçàöèè -íàãðåâàíèÿ â äèàïàçîíå òåìïåðàòóð îò 50 äî 70°C â òå÷åíèå íå ìåíåå 5 ÷ âîññòàíîâëåííîé ïàñòû V [52].  èññëåäîâàíèÿõ [53] ïðåäñòàâëåíû äàííûå, ïîêàçûâàþùèå, ÷òî ÀÏÊ â áîëüøåé ñòåïåíè èíàêòèâèðóåòñÿ íà ìàêñèìóìå òåìïåðàòóðíîãî äèàïàçîíà ïðîöåññà ïàñòåðèçàöèè (60,5°C), ÷åì ïðè íèçêîì óðîâíå (59,5°C). Ýòî ðàçëè÷èå â òåìïåðàòóðå ïàñòåðèçàöèè ìîaeåò ïðèâåñòè ê 2-èëè 3-êðàòíîé ðàçíèöå â ñîäåðaeàíèè ÀÏÊ â ãîòîâîì ïðîäóêòå.…”