Understanding Risks of Coring and Fragmentation of Rubber Stoppers

When it comes to choosing the right container closure system, a significant amount of focus is directed at addressing issues that may be a risk to safety and efficacy of the parenteral drug before it is introduced to a patient. Examples are testing of container closure integrity (CCI) and drug stability. Prior to drug administration by a health care professional, the rubber stopper is pierced with a needle, at least once. Stopper puncture testing also needs to be considered, especially if the closure system will be used in a multi-dose application.

The piercing of a rubber stopper may cause so-called “fragments” or “cores,” i.e., rubber particles that may pose risk to the patient. The risk of fragmentation/coring depends generally on three factors:

• rubber formulation/processing: hardness, thickness of stopper diaphragm, sterilization process, and stopper crimping
• needle: sharpness, siliconization, design of the heel and bevel, and diameter/gauge. Note that although the European Pharmacopeia (EP 3.2.9) specifies a 21 gauge needle for testing, hospitals often use larger needles, such as 18 gauge.
• piercing: angle, speed, direction, number of piercings, and locations of piercing (see West Technical Report 2020/223 Impact of Piercing Techniques on Stopper Coring and Fragmentation)

Testing of these factors will be influenced by the upcoming issuance of USP Chapters <382> (Elastomeric Closure Functionality in Injectable Pharmaceutical Packaging/Delivery Systems) and <1382> (Assessment of Elastomeric Closure Functionality in Injectable Pharmaceutical Packaging/Delivery Systems).

West’s Technical Customer Support (TCS) team can help in selection of the right stopper for a parenteral drug. And through the Integrated Solutions platform, West can design and execute studies needed to evaluate stopper performance. Please visit the West Knowledge Center for scientific insight and detailed technical information on this, and other, key areas.