Requirements on pre-fillable glass syringes
`T. P. Schoenknecht
`Buender Glas
`
`Purpose.
`Pre-fillable glass syringes are used for modern drug formulations containing peptides, antibodies and DNA fragments. The
`composition of such drug containing solution is often very scnsitive to side reactions with the packaging matcrials used,
`leading in ils worst case to a complete inactivationof the active ingredients. Since some year’s silicone oil as well as
`Tungsten residues are known as catalytic substances which can result in such stability problems with parenteral drug
`compositions. The presentation will highlight the latest requirements on the inside siliconization of pre-fillable syringes as
`well as state of the art technology for the reduction of Tungsten residues in modernglass based drug delivery systems.
`Methods.
`
`Atomic Absorption Spectroscopy (AAS) was used to characterize the quantity of silicone sprayed into the glass barrel. A
`study was done to characterize the optimal silicone quantity as well as the best distribution inside the glass barrel for
`biopharmaceutical drug compositionsto be filled into glass syringes. Within this study syringes from 0.5 mlfilling volume
`size to 3 ml were analyzed for their silicone content. Homogeneity of the inside silicone distribution was analyzed by glass
`dust testing and AAS measurement. Interactions between protein based drug molecules withsilicone were characterized by
`gliding force measurements on filled syringes dependent onthesilicone quantity per barrel (0,4 - 1,6 mg)
`Tungsten residues were tested after extraction with dilute nitric acid by ICPMS (Inductively Coupled Plasma Mass
`Spectroscopy) ondifferent syringe formats produced using Tungsien containing and Tungsten-free forming tools.
`
`Results.
`
`The AAS measurements yields an intra batch precision (<5%CV) and accuracy (>10%) from production batch to production
`batch for the total silicone quantity and distribution. Gliding force measurements indicated a lowerlevel of silicone of 0,4 mg
`required for injection usability, which is improved up to 0,8 mg and did not yicld further improvement over 1,6 mg. Protcin
`based drug compositions did not show aneffect on aggregation for silicone quantities between 0,4 and 0,8 mg. Over 0,8 mg
`an increase of the gliding force of 40% wasidentified which results from aggregation.
`Tungsten residues on standard processed syringes were detected to in average 50 ng per syringe with a standard deviation of
`15 ng. Under such Tungsten conditions, modern biotech drugs are none or onlylow affected. The usage of Tungsten free
`forming technology generates complete Tungsten residue free syringes.
`
`Conclusion.
`
`Useful silicone levels for glass made pre-fillable syringe configurations were determined. The Tungsten contaminations of
`syringes out of the standard as well as out of the Tungsten residue improved production process were analyzed. Both together
`offer the optimal combination for the packaging material parenteral biopharmaceutical drug formulations are requiring today
`in order to avoid stability issues.
`
`
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`REGITC00138524
`Regeneron Exhibit 1163.001
`Regeneron v. Novartis
`IPR2021-00816
`
`