03-28-2013 07:17 AM
A recent article published in the Jan/Feb JAPhA evaluted the self-sealing capacity of vials after multiple punctures. The author used the dye ingress method to evaluate the sealing capacity of vial rubber stoppers after several needle punctures. The methods used seemed to comply with USP <381> recommendations. However, the USP <381> only provides general information on the procedures and gives no information on validated instruments.
I conducted a literature search on the subject but found limited information relating to pharmacy compounding. However, there are numerous publications relating to closed-system integrity testing (CSIT) for industry, specifically stability testing. The FDA has provided guidance on CSIT for stability testing in lieu of sterility testing. Within the guidance document it states, "Because of the limitations of sterility tests described below, sterility tests are not recommended as a component of a stability program for confirming the continued sterilty throughout a product's shelf life or dating period." The document goes on to discuss sterility test limitations and the advantages of conducting CSIT methods.
I am curious as to why the dye ingress method and other similar methods are not used more often when conducting studies that evaluate aseptic preparation and manipulations. The sample size needed to show statistical significance in the traditional media fill testing is a huge limitation. Can CSIT methods be used as an alternative? Has anyone used similiar methods at their institution?
Ponto JA. Self-sealing capacity of vial stoppers after multiple needle punctures. JAPhA.2013;53:58-60
FDA Guidance document: http://www.fda.gov/downloads/RegulatoryInformation
04-02-2013 07:17 AM
I read the article but struggled in understanding its applicability to sterility testing and other matters involving USP 797. I don't know if the containers of the two drugs referenced in the chapter were considered multiple dose vials. The test <381> is part of evaluating the container closure system of a MDV. I was disappointed in the generalization of the data reported and would have liked to see the data for each of needle sizes. The fact that there was coring was minimized in my opinion.
CCIT needs to be used for CSPs that are stored for extended periods of time because passing a sterility test alone does not give the complete picture that the CSP and its container will maintain its sterility over time, hence the importance of doing CCIT.