Abstract:Primary containers made of cyclic olefin polymer (COP) have recently gained attention since they may overcome several risks and shortcomings of glass containers as they exhibit a high break resistance, biocompatibility, and homogeneous heat transfer during lyophilization. On the downside, COP is more permeable for gases, which can lead to an ingress of oxygen into the container over time. Since oxidation is an important degradation pathway for monoclonal antibodies (mAbs), the continuous migration of oxygen in… Show more
“…These results indicate that protection of protein formulations from photodegradation can be achieved by minimization of the oxygen content headspace of the primary container or the use of inert gas instead of air ( Qi et al, 2009 ). Thus, reducing the oxygen content in the headspace and using an impermeable oxygen packaging material may lead to a less pronounced photooxidation for light sensitive proteins ( Gupta et al, 2021 ; Masato et al, 2015 ; Won et al, 2020 ; Härdter et al, 2021 ; Landi and Held, 1986 ). Fig.…”
“…These results indicate that protection of protein formulations from photodegradation can be achieved by minimization of the oxygen content headspace of the primary container or the use of inert gas instead of air ( Qi et al, 2009 ). Thus, reducing the oxygen content in the headspace and using an impermeable oxygen packaging material may lead to a less pronounced photooxidation for light sensitive proteins ( Gupta et al, 2021 ; Masato et al, 2015 ; Won et al, 2020 ; Härdter et al, 2021 ; Landi and Held, 1986 ). Fig.…”
“…However, the risk of breakage, lack of chemical compatibility (i.e., formulation pH), low fill-volume, lack of design flexibility, and low manufacturing throughput has propelled innovations towards development of new classes of vials, especially for sensitive and expensive biologic drugs 14 – 16 . A new generation of vials made from polymers has accordingly gained attention in recent years 14 , 17 , 18 . Vials made from polymers such as cyclic olefin polymer (COP) and cyclic olefin copolymer (COC) have been shown to solve some, but not all of the problems of traditional glass vials 14 , 17 – 20 .…”
Implementation of polymeric vials for freeze-dried drug products has been practically non-existent because of unique moisture barrier and thermodynamic technical challenges. Hybrid vials, which combine the benefits of polymer and glass, have been shown to address the challenges of ordinary polymeric vials. Tackling thermodynamic challenges starts with a clear understanding of the heat transfer mechanism. To this end, multi-physics simulations and experimentation were used to compare the heat transfer between hybrid cyclic olefin polymer (COP) vials and borosilicate glass vials during freeze-drying. Parametric models were developed for hybrid COP and glass vials to systematically study the effect of five design parameters based on the arrangement of the vials on a tray inside a lyophilization chamber. Heat transfer in glass vials were dominated by heat conduction with the surrounding vapor, while hybrid COP vials were governed by conduction with the bottom shelf. Furthermore, hybrid COP vials exhibited more consistent heat flow rate and total heat transfer coefficient compared to glass vials, suggesting higher product quality as a result. The distance between adjacent vials and the drug product height were the most important parameters affecting heat transfer irrespective of vial type. Results indicated that hybrid COP vials can be filled to higher fill volumes with higher heat transfer and without the risk of breakage. Results of this study can help design innovative primary packaging systems for freeze drying or optimizing heat transfer for existing glass or hybrid COP vial systems regarding product consistency and drying time.
“…With respect to the container, alternatives to glass vials were investigated, aiming to obtain, among the other results, better heat transfer to the product in the endothermic stages of the process (primary and secondary drying). Härdter et al [ 3 ] considered containers made of cyclic olefin polymer (COP) as they are characterized by a high break resistance, and they are biocompatible and exhibit homogeneous heat transfer. Unfortunately, they are permeable to gases and, thus, require storage in aluminum pouches in the presence of oxygen and moisture absorbers to perform similarly to glass vial storage.…”
Freeze-drying, also known as lyophilization, is a process that facilitates the removal of water through sublimation from a frozen product (primary drying) [...]
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