Traditionally, companies developing sterile drug products rely on a risk-based approach to justify their container closure components during early-stage product development. This often results in forging ahead with a sole combination of primary packaging components. Subsequently, the basis for extractables and leachables, stability, and biocompatibility studies, to name a few, are built off these decisions. All is well until the combination of container closure components proves not to be integral per the product specification. At the point of an Out of Specification (OOS), development scientists are faced with the possibility of having to change the primary packaging components and potentially having to scrap development data. This scenario can be avoided by assessing the Container Closure Integrity (CCI) performance of an assembly consisting of multiple primary packaging components early on during product development. Not only can CCI tools be used for assessing sterility, they can also be leveraged to assess product attributes and headspace conditions. Special care should be taken when unique product attributes, abnormal manufacturing conditions, unique storage conditions, or novel combinations of primary package components are utilized. Often, the more ‘’unique’’ the product or process is, the more one should consider heightened scrutiny to processing parameters and test results. Executing preliminary CCI Testing under a Design of Experiments (DoE) early on in product development is a prudent way to ensure the container system design is robust.
It is easy to overlook manufacturing process design in early-stage development, especially for firms who do not have established Quality by Design (QbD) programs in place. After all, early batches are made with the primary focus on assessing initial feasibility of safety and efficacy. However, it is important to consider that these batches provide the basis for subsequent modifications to batch instructions, in-process controls, release specs and storage conditions. Therefore, taking a discerning look at the processing inputs and the resulting outputs is key. Furthermore, assessing the outputs for sterile injectable drugs is critical, due to the sensitive nature of these types of products.
Take, for example, a vial product that is sensitive to degradation and has unique physiochemical properties (hence requiring unique manufacturing parameters): A firm would want to utilize early-stage development batches to modify processing parameters under a DoE. The resultant units would be assessed using CCI tools and subjected to various environmental or temperature cycling conditions. The data gathered would help development scientists determine what parameters have the biggest effect on the end product and thus where to direct focus for subsequent manufacturing campaigns. CCI method selection depends upon the container system being evaluated; a single method is not suitable for all systems. Cryopak Testing Center (CTC) can help. Let our experts assist with the determination of the right test method for your system.
CTC’s CCI division is privileged to offer pharmaceutical and biotech companies, along with their respective medical device manufacturers, with the most recent deterministic capabilities following USP <1207> recommendations and guidelines. Our experienced scientists are dedicated to CCI and the full range of methods, and will develop, validate and execute CCIT methods to support your product development and design verification programs. We can provide tailored expertise to design and execute a CCI study based on your system, providing the support you need.