To comply with regulatory expectations and ensure product safety, it’s critical for biopharma manufacturers to demonstrate and maintain container closure integrity (CCI) for their products. Substantial improvements in container closure integrity testing (CCIT) options over the past decade position companies in the biopharma space to better handle these complex challenges. Here are three key CCIT trends.
Probabilistic to deterministic methodology: Access hard data from deterministic methods
Probabilistic test methods, such as dye ingress or microbial ingress, rely on a series of probabilistic events to generate accurate results. These methods are rapidly falling out of favor with regulatory bodies in the U.S. and Europe, as well as with internal regulatory groups.
Deterministic methods rely on a predictable chain of events driven by known physicochemical phenomena. One example: Measuring the exact helium leak rate of a vial as opposed to visually inspecting a vial to see if there’s dye inside post-immersion. By definition, deterministic methods do not incorporate probabilistic steps such as human observation of dye.
If regulatory agencies and guidance documents, such as USP <1207>, continue to move toward deterministic and quantitative CCI analyses, this industry trend may soon become an industry requirement.
Reactive vs. preventative programs: Apply a preventative program to reduce risk
With reactive programs, clients aim to understand leakage issues that arise late in the product development or release process. Now, most clients perform preventative studies, where package integrity is characterized up front, before the product is put into them, or perhaps even before final package components are selected, to gain a robust understanding of how those packages will perform in their most basic state. This concept is referred to in USP <1207> as “inherent integrity.”
This trend represents a shift from treating CCIT as a check-box to performing it early in the product-package development process. Data generated through preventative studies can support changes to the package components or their assembly, preventing costly component changes down the road and resulting in safer, less recall-prone packaging.
The growing biologics and biosimilars market: Take a multipronged approach to combination products
Five years ago, most sterile packages we worked with were vial-based. The products would typically be reconstituted, if not already in liquid form, and drawn into a syringe at the time of dose delivery, often in a medical setting. Today, we see more prefilled syringes and combination products, such as autoinjectors, designed to quickly deliver a premeasured dose of medication in a range of environments. These combination products present some challenges to CCI, as the primary package containing the dose is within a device body, limiting access and therefore the ability to detect small leaks.
Thus, CCIT now takes a multipronged approach to those types of package systems:
1. The most sensitive technologies are leveraged to evaluate inherent integrity of the empty primary package, such as the plunger-barrel interface of a syringe.
2. Another method may be employed to test the product-filled primary package.
3. A third, less sensitive method may be employed to test the fully assembled device.
This multipronged approach serves to paint an overall picture of the entire system and its integrity through its lifecycle. It’s a holistic approach to qualifying today’s unique package systems with respect to CCIT.
Learn more about industry and regulatory trends, as well as how to incorporate container closure integrity testing into your program. Watch the Pharmaceutical Outsourcing interview.