Mass Extraction Container Closure Integrity Physical Testing Method Development for Parenteral Container Closure Systems

Abstract

Sterile products must maintain their sterility over their entire shelf life. Container closure systems such as those found in syringes and vials provide a seal between rubber and glass containers. This seal must be ensured to maintain product sterility. A mass extraction system has been developed to check container closure integrity for a variety of container closure systems such as vials, syringes, and cartridges. In order to demonstrate the method's capability, various types of defects (e.g., glass micropipette, laser drill, wire) were created in syringes and vials and were tested. This study demonstrated that a mass extraction system was able to distinguish between intact samples and samples with 2 μm defects reliably when the defect was exposed to air, water, placebo, or drug product (3 mg/mL concentration) solution. Also, it was verified that the method showed consistent results, and was able to determine the acceptance limit using 3σ for syringes and 6σ for vials.

Advances in Container Closure Integrity Testing

“…Recent technologies utilizing mass extraction (Yoon et al 2012 ), HVLD (Möll et al 1998 ), and vacuum decay (Wolf 2009b ) have demonstrated reliable detection of CCI defects of 5-10 μm or better. These technologies are based on quantitative measurement of certain sample characteristics that can be further correlated to presence and/or sizes of CCI defects; therefore, they can be readily validated with quantitative results.…”

“…Conventional testing methods, such as dye ingress and microbial ingress tests, have been used in the industry for decades. Recent development focused on instrumentation-based technologies, such as high voltage leak detection (HVLD) (Möll et al 1998 ), vacuum/pressure decay (Wolf 2009a ), mass extraction (Yoon et al 2012 ), and tracer gas detection (helium leak detection (Kirsch et al 1997 ), headspace oxygen testing (Brigitte 2012 ), etc. ) has successfully demonstrated improved detection capabilities.…”

“…Mass extraction testing (Yoon et al 2012 ) is closely related to vacuum decay technology. Instead of measuring the pressure increases, mass extraction directly measures the mass fl ow rate of the volatile content (i.e., headspace gas and/or liquid vapor) extracted from the container samples using a fl ow sensor connected to a vacuum reservoir.…”