Causes of Coring and Fragmentation in the Field
One of the challenges a drug manufacturer faces is controlling the drug product at the point-of-use in a hospital or clinical environment. Often the method of vial access is variable, leading to an increased risk of harmful patient outcomes such as stopper cores or fragments entering into the drug product, which can contribute to cardiovascular events. There are a number of causes that contribute to stopper coring and fragmentation in the field that depend primarily on the technique of the practitioner and the properties of the elastomeric closure.
Causes of Coring or Fragmentation (Technique):
- Needle type – it has been observed that blunt needle tips have a much greater tendency to produce fragmentation than sharp beveled needles.
- Needle gauge – needles larger than a 21-gauge tend to promote fragmentation.
- Needle siliconization – needles with low or inconsistent siliconization cause increased coring and fragmentation.
- Needle reuse – reuse will dull a needle, remove silicone and increase the chance of coring and fragmentation.
- Force of puncture – higher needle insertion forces increase the tendency for coring.
- Angle of puncture – needle insertion at a 45° angle to the plane of the stopper increases the likelihood of coring.
- Number of punctures – multiple stopper punctures greatly increase the chance of coring.
- Incorrect use – using a spike on a stopper design that was not intended to receive a spike will produce fragments.
Causes of Coring or Fragmentation (Closure Properties):
- Elastomer formulation – natural rubber and synthetic isoprene formulations typically have more robust functional properties than butyl formulations and show reduced coring because of their increased tensile strength.
- Configuration – the stopper diaphragm thickness typically plays a role in coring. Generally, thinner stopper diaphragms reduce the likelihood of coring.
- Siliconization of the closure – unsiliconized closures may see increased coring results.
- Closure processing – excessive processing of closures, particularly high gamma irradiation, may degrade the elastomer and result in increased coring.
To reduce the possibility of coring, West recommends increased field education on proper needle/spike usage and selection. Additionally, the drug manufacturer can help prevent coring through the proper selection of elastomer formulation and design for end use. For known multidose applications, synthetic isoprenes and specific low-coring stopper designs are available. Vial adapters are another way for the drug manufacture to ensure normalized vial access in the field and multiple dose withdrawal with a single stopper puncture. Finally, understanding the impact of processing on the physical properties of the elastomeric formulation is an essential aspect for reduced coring. Please contact your West Technical Account Specialist to discuss some low-coring stopper options.