Ex Situ and In Situ Characterization of Vaccine Suspensions in Pre-Filled Syringes.

Ex situ and in situ techniques were used to characterize the suspended phase over time for a vaccine drug product supplied in syringes. Micro-computed tomography was used to characterize the suspended sediment in situ in the syringe, while traditional techniques such as particle size distribution, charge (zeta potential), settling rate, and front-faced fluorescence were used to characterize the suspension ex situ. In addition, analytical chemical measurements were conducted in parallel during the course of the study. The ex situ and in situ techniques together with the chemical analyses provided different sets of data, but all leading to the same conclusion that the older, hard to re-disperse vaccine product syringes were similar in product quality attributes (both physical and chemical) to the freshly made, easy to re-disperse syringes. Longer re-dispersion time with age was not a result of any altered physical or chemical attributes of the product but simply because of the distance travelled by the sediment from the neck of the syringe barrel deeper into the bore of the syringe over time under the influence of gravity in the tip down orientation, making it harder for the continuous external phase to access the sediment in the bore and enable easy re-dispersion.