Issue link: https://www.e-digitaleditions.com/i/1248960
Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2020 21 Pharmaceutical Services. "These challenges include the potential for interactions with many substances, which is why glass has historically been the material of choice for primary containers, including prefilled syringes. However, due to technological advances in polymer chemistry, plastic prefilled syringes are now beginning to emerge on the market." Looking beyond glass and plastic, I'ons notes that prefilled syringes comprise other materials that can also interact with biologic therapeutics. For example, tungsten—frequently used for needle mounting— and silicone—routinely applied in formulations to the syringe barrel for lubrication of the plunger—can interact with biological substances. "Newer innova- tions in syringe technology are exploring ways to limit or remove these substances," I'ons states. Common materials used for prefilled syringes include cyclic olefin polymer, cyclic olefin copoly- mer, polypropylene, and polycarbonate, adds Sacha. "However, there are less advances in the materials of construction than there are in the types of syringes that are available," he says. "For example, there are syringes in development that require substantially lower overfill volumes. There is also a syringe in de- velopment that consists of multiple layers that include an oxygen barrier. And, there are needles available with narrow diameters to reduce pain upon injection." Safety considerations When formulating biologics, the solution can often be highly viscous, which leads to specific challenges in terms of administration via prefilled syringes. "Viscosity can impact variables such as force to inject, dose delivery time, and needle gauge which all need to be determined and tested," states I'ons. Agreeing, Sacha emphasizes that although there is less concern for breakages with syringes than glass vials, viscosity can cause difficulties and, as a re- sult, early studies often include flow of the solution through the needle intended for use and conducting break force and glide force studies to monitor the pressure needed to initiate movement of the plunger and continuation of the movement. "Additionally, challenges with biologics filled into sy- ringes typically include possible interactions with the molecule and silicone used to lubricate the barrel of the syringe and the needle," Sacha continues. "Interactions with silicone can lead to the formation of aggregates." Aggregates are well known to have a negative impact on the efficacy and safety of biologic drugs, potentially giving rise to harmful side effects for patients. Discussing the intricacies of combination prod- ucts, I'ons adds that human factors (HF) are essen- tial considerations in the development and regula- tory approval processes. "A rigorous HF process is key to understanding user interaction and shaping user-centered risk management relating to the drug delivery device," he says. "HF will examine the de- vice in a series of use scenarios with a sample of all intended users, including those with impairments, to ensure safe and effective use." In I'ons opinion, a key safety consideration for com- bination products using prefilled syringes is effective needle shielding, which also requires companies to be compliant with needlestick prevention regulations "Viscosity can impact variables such as force to inject, dose delivery time, and needle gauge which all need to be determined and tested." —George I'ons, Owen Mumford