Rubber stopper sterilization

Can anyone recommend a published report or paper on sterilization of rubber stoppers for use on pharmaceutical vials? I am interested in regulatory guidance, study protocols, use of direct inoculation of spores onto stoppers, etc. Thank you.

You can look these

[b]US Food and Drug Administration. Guidance for industry: Container closure systems for packaging drugs and biologics, chemistry, manufacturing, and control documentation. Rockville, MD; 1999 May.

Europeans Commission (Enterprise Directorate General). EMEA guideline on plastic immediate packaging materials. Brussels, Belgium; 2005 May.

USP. General chapter <381> elastomeric closure for injections.

European Pharmacopeia. Chapter 3. Materials for containers and containers.[/b]

One issue related to worldwide pharmaceutical distribution is that of regional compendial testing. These are basic tests that must be conducted on materials that will be used for pharmaceutical stoppers. This basic testing is necessary for regulatory submissions and each region has its own documentation requirements and protocol demands.

United States: Testing specific to stoppers in the United States Pharmacopoeia United States Pharmacopoeia, the nongovernmental organization that promotes public health and safety by establishing state-of-the-art standards for medications. Also called
USP-NF. 2. Physicochemical Series and Sections 87 and 88: Biological Testing.

Europe: For submissions to Europe, closures must be qualified through a series of tests from the Pharmacopoeia pharmacopoeia or pharmocopeia ,authoritative publication designating the properties, action, use, dosage, and standards of strength and purity of drugs. of Europe (Ph. Eur. Section 3.2.9). This testing includes physicochemical testing and functional testing of the rubber closures.

Japan: For submission to Japan, the Japanese Pharmacopoeia (JP), Section 59, lists physicochemical and biological series testing.

Bovine Spongiform Encephalopathybovine spongiform encephalopathy (BSE) and Transmissible Spongiform Encephalopathy (TSE ).Since some animal derived raw materials are used as ingredients in rubber closures, there has been much industry concern, primarily driven from Europe to other regions of the world, in relationship to this issue.

The European Medicines Agency (EMEA) has recently given clear direction on this issue in relationship to pharmaceutical packaging. Their concern is only for primary packaging components, those that are in direct contact with the drug, not secondary components.

You can also look PDA site:


When you spike biological Indicator directly on the stopper (inside the well), and once you test the growth of these in media and absence of growth after sterilization provides assurance that the stopper itself has received enough lethality to provide total inactivation of the test organism.

You can also use spore strips inside the containers of the rubber bungs gives you an idea of lathality or steam penetration into the container.

Please look the presentation attached about sterilization.

Rubber stoppers.pdf (696.4 KB)