Integrity of the closure of a drug product container/delivery systems is crucial to guarantee safety and efficacy. Methods (deterministic and probabilistic) to measure this have recently been set forth in USP Chapter 1207. This section presents papers discussing methods (e.g., helium leak, gas headspace, high-voltage leak detection) and their application to various systems.
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Low temperature (from 8degC to -180degC) storage is essential for preserving the efficacy of many biologic drug products. Evaluating CCI of containment/delivery systems under such conditions is a challenge. West has undertaken a three-phase approach to address this. Commercial tracer gas (helium) leak detection equipment was modified (patent pending) to enable real-time evaluation at low temperature. This is especially useful for high-throughput evaluations (i.e., quickly identifying unsuitable systems). Coupled with this are laser-based headspace analysis to examine gas ingress over time and high-voltage leak detection to examine seal integrity over time. Together, a complete picture of CCI performance can be obtained. Presented will be how this approach is applied to systems comprising rubber stoppers/plungers with vials/syringes comprising glass and polymer.
Pre-filled syringe and cartridge systems pose unique challenges regarding container closure integrity (CCI) analysis. With the advent of USP chapter <1207>, the industry is now better guided regarding applicable technology and proper method validation processes. This presentation will examine how deterministic methods can be applied, individually, and in combination, to evaluate syringes and cartridges at temperatures from ambient to cryogenic (critical for biologic and cell therapies).
The container closure system (CCS) determines container closure integrity (CCI) performance, and CCI quality is essential for drug product integrity throughout the entire sealed drug product life cycle.
Radiolabeled protein molecules are used to demonstrate that there is less adhesion to a vial made of Daikyo Crystal Zenith® cyclic olefin polymer (COP) than to a glass vial, and that COP enables better recovery of protein.
<p><em>A. Leece, et al. Applied Radiation and Isotopes, 80, 99-102 (2013)</em></p>
<p id="FullPage_d6e5d6e32fe341550505091627">L. Waxman and V. Vilavalam<span style="text-decoration: underline;">.</span><em id="FullPage_37a5b9334dd851550505091627"> Drug Development and Delivery (May 2014)</em></p>
<p id="FullPage_52d1e96723ec41550505091627">This article describes the use of cyclic olefin polymer in closure systems for radiopharmaceuticals and its potential for maintaining drug activity by minimizing loss through adsorption to container surfaces.</p>
Contained is summary discussion of seven plenary sessions of the subject PDA conference.<br />
Plenary 1: The Future of Drug Delivery<br />
Plenary 2: Strategies for Safety Evaluation<br />
Plenary 3: Leachables and Extractables for Combination Products that Include Both Drugs and Devices<br />
Plenary 4: Holistic Safety and Quality Assessment<br />
Plenary 5: Particle Challenges Associated with Delivery Systems and Devices<br />
Plenary 6: Compatibility of Delivery Systems with Biologics<br />
Plenary 7: Quality Considerations for Combination Products and Device<br />
<em>(co-sponsored with the Product Quality Research Institute (PQRI), Oct. 2–3, in Washington, D.C.)</em>
This article considers how changes to USP Chapter 1207 will affect the measurement of container closure integrity for drug product packaging systems.
<p><em>H. Forcinio. Pharmaceutical Technology, 39 (4) 76-77 (2015)</em></p>
<p>This article describes properties of cyclic olefin polymer and its ability to maintain container closure integrity under cryogenic conditions, as well as its transparency and fracture resistance.
<p><em>PDA Letter written by James McCaw of West Pharmaceutical Services, Inc.</em></p>
This article considers the fundamentals of gas headspace analysis for the measurement of container closure integrity – the physics of the process is described along with the types of containers for which it is suitable.
<p><em>D.I. Duncan and J.R. Veale (Lighthouse Instruments)</em></p>
This presentation considers several different methods of measuring container closure integrity, and compares their relative utilities: (a) vacuum decay (loss of vacuum in evacuated chamber due to failure of container), dye ingress (visual observation of colorized fluid moving into container), ultrasonic (air pockets where container components join).
<p><em>H. Wolf (PTI Inspection Systems)</em></p>
This poster considers the use of gas headspace analysis for the measurement of container closure integrity of syringes. The method can distinguish differences in gas permeability between plunger and tip, and between staked needle and Luer lock configurations.
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<p><em>J.R. Veale and K.G. Victor (Lighthouse Instruments). PDA Universe of Pre-filled Syringes & Injection Devices Conference (2016)</em></p>
This review article considers various methods of container closure integrity testing for the major types of drug product containers (vials, syringes, IV bags) - in view of regulatory requirements.
<p><em>Edward K. White. Journal of Validation Technology (Spring 2012)</em></p>
<p>This article describes the many benefits of Daikyo Crystal Zenith<sup>®</sup> cyclic olefin polymer versus glass for low-temperature storage of drug products.</p>
<p><em>W. Winters. Pharmaceutical Online (July 25, 2017)</em></p>