This technical report is a consensus-based resource surrounding the challenges encountered in using complex package systems and introduces important elements to consider in decision-making. It also offers an examination of the technologies available for package integrity testing not yet established by peer-reviewed research. This technical report focuses on the challenges facing the pharmaceutical industry that use complex packaging systems for sterile drugs and biologics (e.g., syringes, syringe assemblies, bulk containers). It also presents information on some innovative methods for package integrity testing using existing technologies, including the potential impact of cryogenic conditions. The intent is to update information and incorporate experiential learning which is not addressed in PDA Technical Report 27 and USP<1207>. It also serves as a technical resource, focusing particularly on sterile products and encouraging a risk-based approach and leveraging testing to better understand, analyze, and eliminate the risks during developmental phases. Use of the appropriate testing during each manufacturing phase can help in evaluating and mitigating residual risks.