Evaluation Of A Novel Cyclic Olefin Polymer Container System For Storing Adeno-Associated Virus

By Rui Li, Samuel A. Molina, Katie Glen, Jon Harriman, Crystal Kraft, Vidya Murthy, Robert Thomas, Alexander Lyness

One of the most effective vehicles for delivery of therapeutic nucleic acids are viral vectors, demonstrated by their utility in many commercial cell and gene therapy products. Despite their success, gaps remain in the optimization of viral vector storage. Traditional polypropylene snap- and screw-cap vials used in academic and research settings do not have the closure integrity or inert properties required for storage of a commercial drug product. Further, glass vials commonly used for biologic drug products have not been fully characterized in the context of viral vectors, which have a need for colder storage temperatures and an associated need for increased break resistance. In the present work, three vial types used for biologic product storage, cyclic olefin polymer (COP), polypropylene (PP), and glass, were evaluated for the preservation of adeno-associated virus (AAV) during ultra-low temperature storage.

Adeno-associated virus serotype 2 (AAV2) was one of the first adenovirus serotypes evaluated as viral vector to deliver normal human gene for treating genetic disease and resulted in the first Food and Drug Administration (FDA) approved gene therapy drug. The new drug modality is challenging to manufacture and to store, requiring container closure integrity at -80°C. Previously, West demonstrated the utility of Daikyo Crystal Zenith® (CZ)  container systems at cryogenic temperatures [1] as well as outlined the advantages of working with CZ vials for cell therapy storage [2, 3]. This report is focused on the utility of cyclic olefin polymer CZ vials for -80°C storage of AAV material and determining the relative performance of CZ vials relative to glass vials, and traditional PP cryovials for the preservation of purified commercial research use only grade AAV2 at ultra-cold temperatures.

The utility of viral vectors used for both in-process manufacturing of cellular therapies and as final drug product drives a critical need for scalable container systems compatible with various viral vectors and their manufacturing processes. PP screw-cap cryovials commonly used for research are not specified to operate at the -80°C required for long term storage of viral vectors. PP vials are not well suited for production considering all four gene therapies approved by the FDA are in pharmaceutical grade container systems aimed at controlling issues like the inherent risk for loss of container closure integrity and sterility [3, 4, 5]. The CZ container system has a low extractables profile, high optical clarity, and a rubber stopper-aluminum seal closure that provides a hermetic seal. This study investigates the suitability of a container system composed of the novel COP CZ as an alternative for the ultra-cold storage of therapeutically relevant AAV viral vectors.