Q-288. Parametric Release of Large Volume Parenteral Solution (LVPS) Through Accumulated Lethality (F-value) Associated to Biological indicator (BI) Lethality

T. C. V. Penna1, M. Ishii1, F. N. Dias2, F. Santiago3, S. Nogaroto4;
1Fac. CiOncias FarmacOuticas-Univ. São Paulo, São Paulo, BRAZIL, 2Fac. Ciências Farmacêuticas-Univ. São Paulo, São Paulo, BRAZIL, 3Aster Produtos Médicos Hospitalares, Sorocaba, São Paulo, BRAZIL, 4Nipro Med., Srocaba, São Paulo, BRAZIL.

Parametric release (PR) of large volume parenteral solution (LVPS) aims the release of terminally sterilized lots of products based upon the compliance with well defined and qualified critical parameters, which are monitored in every corresponding cycle of sterilization process. Therefore, once a sterilization process is fully validated and operates consistently, a combination of physical sterilization data, expressed in accumulated lethality (F-value) and associated to biological indicator (BI) resistance (D-value) can provide more accurate information than the sterility test, regarding the release of terminally sterilized product to the marketplace. The operational performance in the processing of LVPS (125-1000mL polyethylene bottles) at 102oC/60 min, was periodically evaluated with thermal sensors placed in cold points of the 17,000L capacity autoclave chamber (heated and cooled through water shower in continuous circulation). For the same autoclave and maximum load (between 6541 and 15.400 bottles), the physically measured lethality expressed in F-values (102oC, z=10OC) varied from 68-74min (sensor 1) and from 61-68min (sensor 2) independently of LVPS and bottle volume, assuring uniformity of heat distribution. The process provided a SAL of ≥10-6 for the BI of 106 spores of Bacillus atrophaeus ATCC9372 with D-values (102oC) of 2.5±0.5 min (0.9% NaCl, 5%-10% glucose, Ringer’s plus lactate, 20% manitol). Considering two autoclaves (102OC/60min) and maximum load of 6540 bottles of Ringer’s plus lactate, for five consecutives sterilizations, the F values ranged from 51 to 56 min in autoclave 1 and from 61 to 72 min in autoclave 2. Both autoclaves processes exceeded from 4-5 times the 12 log10 cycles of BI, although the moist heat distribution in autoclave 1 showed higher homogeneity than that in autoclave 2. The process showed capability to exceed the requirements necessary to inactivate bioburden to > 10-6 PNS (probability of nonsterility), the test for endotoxin was confirmed < 0.125 EU. As a consequence, the LVPS can be safely delivered to the market without the sterility test.