Preparing eye drops from injectable specialties: using a peristaltic pump, from reconstitution to distribution

Context
Anti-infectious eye drops prepared from injectable specialties (amphotericin B, ceftazidime, etc.) represent 1,100 units prepared each year as hospital preparations in our department. Their preparation is not automated and requires many repetitive manual steps. The purpose of this study is to validate the use of a peristaltic pump (Repeater®, Baxter) for all steps in the preparation of these eye drops, from reconstitution to filling.

Materials and methods
The pump was first qualified by checking its accuracy and precision using gravimetric measurements of volumes of 5 and 10 mL of water delivered by the pump (10 repetitions). To validate accuracy, mean deviations from true values had to be within ±2%, and for precision, coefficients of variation had to be less than 5%.
The procedure for preparing the eye drops was written like that: installation of the sterile captive tubing on the pump and of the reconstitution solvent, calibration of the pump for the reconstitution volume, reconstitution of the vials, withdrawal of the contents of the vials using the reverse mode into a bag, calibration of the pump for the distribution volume and distribution into the eye drop vials with passage through a 0.22 µm sterilizing filter. All these steps are carried out in an isolator (class A).
A test batch of 30 eye drops of amphotericin B 5 g/L was prepared. Eyedrops were weighed to check the uniformity of volumes dispensed by the pump, using the same parameters as for validation of accuracy and precision. The concentration of amphotericin B was checked for ten eye drops by liquid chromatography, and a sterility check was carried out on three eye drops.

Results
For accuracy, mean deviations from true values were -0.2% and -0.6% for 5 and 10 mL. For precision, the coefficients of variation were 0.26% and 0.14% for 5 and 10 mL. The test batch was used to validate the procedure. For gravimetric control of the test batch vials, the mean deviation from the true value was 0.4% and the coefficient of variation 0.67%. The average amphotericin B concentration of the ten eye drops tested was 4.91 g/L, and all three eye drops tested were sterile. These results all comply with the specifications set.

Conclusion
This new preparation method has been validated and applied to amphotericin B, ceftazidime and vancomycin eye drops. The pump installation and calibration steps increase preparation time, but the elimination of manual steps has enabled batch sizes to be doubled, thus reducing preparation frequency. Over the past 6 months, 15 batches have been prepared using this new operating procedure, with all physico-chemical and microbiological controls being compliant.

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