The European Directorate for the Quality of Medicines & HealthCare (EDQM) has published the revised general chapter on Rubber closures for containers for aqueous parenteral preparations, for powders and for freeze-dried powders (3.2.9) in European Pharmacopoeia Supplement 11.1, with an implementation date of 1 April 2023.
This general chapter is mandatory for aqueous parenteral preparations since it is referred to in the general monograph on Pharmaceutical preparations (2619) and in the dosage form monograph Parenteral preparations (0520), both of which are legally binding.
The revised chapter was first published in Pharmeuropa 33.2 for public consultation. The comments received were reviewed by the group of experts responsible for the text (Group 16) before the finalised text was adopted by the European Pharmacopoeia Commission at its 172nd session in March 2022.
The overall aim of the revision process was to update the text and bring it in line with current practices. The key changes to several sections are detailed below.
- The Definition and scope section has been changed to prohibit the use of natural rubber latex because of its allergenic potential. However, dry natural rubber is permitted since any allergens it contains are removed during processing.
- IR has been maintained as the basic identification technique for rubber, and the Total ash test has become optional and complementary. A list of other techniques that can be used is now also included.
- Acidity or alkalinity has been revised to explain how to choose the titrant depending on the colour of the indicator.
- For the Absorbance test, filtration is now prescribed for turbid or hazy solutions only.
- The test for Extractable heavy metals has been deleted to align with ICH Q3D and the Ph. Eur. policy on Elemental impurities. Rubber closures are considered to be part of the container closure system and as such, their impact on the level of elemental impurities is evaluated as part of the risk assessment for the pharmaceutical product. The test for Extractable zinc has been kept as zinc is often intentionally added during the manufacturing process and there is therefore a high probability that it will be found in rubber samples.
- The introduction to the Functional tests section has been expanded to indicate when to perform, potentially adapt or omit these tests which, due to the many different types of containers and corresponding rubber closures used, might not always be applicable.
- Fragmentation: the specific testing procedure for closures used for dry preparations has been deleted. Allowing the sample to stand for 16 h at room temperature proved unnecessary and this requirement has therefore been deleted from the procedure to ease the running of the test.
As mentioned above, the revised chapter will come into force on 1 April 2023.
See also:
- European Pharmacopoeia 11th Edition
- European Pharmacopoeia Commission
- European Pharmacopoeia work programme