Container Closure Integrity Testing Method Development And Validation For Prefilled Syringes

By Lei Li

Introduction

Utilization of prefilled syringes as a preferred container closure system for biologics has been increasing ^[1]. As a primary container closure system, prefilled syringes must provide an integral barrier that protects drug product stability and sterility throughout its entire shelf life. Drug manufacturers are required to check and demonstrate the system is capable of maintaining its microbial barrier integrity ^{[2, 3]}. In 2008, FDA further promoted container and closure system integrity (CCI) testing as a component of the stability protocol for sterile products

In response to the increasing regulatory expectations, the pharmaceutical industry has driven and witnessed significant technical advancements in CCI testing ^[5]. Instrumentation-based technologies, such as high voltage leak detection (HVLD) ^[6], vacuum/ pressure decay ^[7], mass extraction ^[8], and tracer gas detection (helium, oxygen etc.) ^{[9, 10]}, have emerged and demonstrated improved detection capabilities compared to conventional dye and microbial ingress methods. Many of the technologies have been used for on-line 100% inspection and/or drug product stability CCI testing. In this article, we highlight our current thinking in an attempt to devise a systematic approach for CCI testing method selection, development, and validation.