Blogs

The FDA states: Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality or purity of the drug beyond the official or established requirements.*  While they make this statement, there is no prescription offered in actually how to execute an extractables and leachables evaluation, which is, of course, an essential aspect of demonstrating suitability of containers and closures.

The FDA has approved over twenty (20) cell and gene therapy drugs, and with the rapid growth of the cell and gene therapy market, there is greater demand than ever to demonstrate container-closure integrity (CCI) at ultra-low temperatures. To preserve the product’s efficacy, most cell and gene therapy drugs are stored at temperatures below -60ºC. Many of these products are packaged in either vial systems or cryogenic freezing bags. While each of these container-closure systems poses a unique challenge for the evaluation of CCI at ultra-low temperatures, the discussion in this blog focuses specifically on vial systems.

Drug developers must understand and mitigate the risk of various chemical entities (leachables) migrating from any material that comes into contact with their drug product. Failure to execute an appropriate extractables and leachables assessment could lead to failures in meeting agency expectations and a delay in drug development timelines.

While medications can provide life-saving solutions to patients, they can also result in harm to medical personnel who might suffer unintended exposure to potent drugs. The seemingly simple act of placing a syringe needle into a septum-sealed vial can result in inadvertent needle-sticks, with potential drug exposure. Additionally, the transfer of potent chemotherapeutic drugs can result in fugitive droplets or volatilization of the drugs and therefore personnel exposure.

The pharmaceutical and biotech industries face many challenges when selecting the appropriate stopper, seal, and vial combination for a drug product. Further compounding these challenges is the manufacturing capability of each component supplier. Lot to lot variation can result in components that had maintained container closure integrity (CCI) and visual acceptance during development unexpectedly failing during production. Therefore, it is important to take a system approach when selecting vial container closure system (CCS) components and designing a fill-finish process. To minimize the risk for sterility failure and maximize performance, it is essential to understand not just the process, but also the historical and trending performance of the selected parenteral packaging components. As a result, West has built the DeltaCube™ Modeling Platform to facilitate data-driven selection and optimization of vial CCS components.

The drug and packaging industries have always been extremely conscientious to ensure that anything added to a delivery device to improve performance (e.g., silicone oil used to coat the inner surface of a syringe barrel), does not affect a drug’s efficacy or safety. But what about the converse? How do we make sure that the drug, or more specifically its added excipients, does not affect the delivery system’s performance? The term excipient refers to any member of a broad group of surfactants, preservatives, tonicity agents, and buffers which formulation scientists take great care to balance in order to provide the drug, such as a therapeutic protein, in its most effective and deliverable state.