Flow rate conservation test of Folfusor SV 2ml/h diffusers: towards an extension of expiry date?

The anticancer preparation unit of our university hospital center produces batches of hospital preparations (HP) of 2-day diffusers of 5-fluorouracil (5FU) dosed at 4 g, 4.5 g and 5 g using a distribution pump. The physicochemical stability of 5FU packaged in Folfusor^® diffusers has been demonstrated by the laboratory over a period of 42 days (D). A study in 2015 on Homepump^® diffusers demonstrated the preservation of the perfusion rate with a preparation 14 D in advance (2 ml/h +/- 15%). The expiry period for our batches of HP was therefore set at 14 D. Since then, a market change has been made in favor of Folfusor^® SV 2ml/h diffusers.

The objective is to evaluate the flow rate conservation of these diffusers over a storage period of 28 days in order to extend the expiry date of these HP.

An average flow rate test on 30 diffusers was carried out. According to the ISO 28620:2020 standard, the flow rate accuracy of portable diffusers is +/-15% between [1.7 -2.3 ml/h]. The diffusers pre-filled with a pump with 103 ml of 0.9% NaCl were stored at room temperature until unclamping, a condition identical to the batches carried out routinely. The unclamping of n=3 diffusers took place on D0, D14, D15, D16, D17, D21, D22, D23, D24 and D28. Once unclamped, they were connected to an empty bag to allow flow and placed in an oven at 36.7° (body temperature). The flow rate is calculated by determining the diffused volume by weighing the bag and the diffusers at different diffusion times (H0, H3, H7, H24, H32, H48, H50, H53). This same experiment was carried out on 3 5FU diffusers from our HP batches declamped respectively at D26, D28 and D42.

The average flow rate calculated over 48 hours for the N=30 diffusers is 2.08 +/- 0.07 ml/h. For all diffusers, all of the NaCl was diffused at H48. However, over the 48 hours, N=5 diffusers showed significant variations in flow rate: two diffusers (D14 and D16) reached a compliant flow rate from H7 and H24, three other diffusers D0 (1) and D22 (2) had a flow rate increased punctually: 2.44 ml/h at H32 and 2.34 ml/h and 2.4 ml/h at H7 to then return to the standards at the other analysis times. Concerning the 5FU diffusers at D26 and D28 the average flow rate over 48 hours was respectively 2.05 +/- 0.07 ml/h and 2.0 +/- 0.08 ml/h, i.e. within the standards, and at D42 the diffuser did not diffuse at all.

All diffusers (N=30) maintained an average flow rate at H48 compliant with the standard in force up to 28 days after their preparation. Additional flow rate variations (<10%) may be due to NaCl according to Baxter^® data. These data allow for extending the unclamping deadline to 28 days for a 30 day expiration, increasing batch sizes and reducing expiration losses.