September 7, 2021: Pharmaceutical Interview Questions and Answers
#PreferredMethod of sterilization #NumberOfSterilizationFiltersRecommendedByEUAnnex1 #FilterIntegrityTestingWhenandWhy
1. What is preferred method of sterilization as per EU Annex 1?
Filtration alone is not considered sufficient when sterilisation in the final container is possible. With regard to methods currently available, steam sterilisation is to be preferred. If the product cannot be sterilised in the final container, solutions or liquids can be filtered through a sterile filter of nominal pore size of 0.22 micron (or less), or with at least equivalent micro-organism retaining properties, into a previously sterilised container. Such filters can remove most bacteria and moulds, but not all viruses or mycoplasmas. Consideration should be given to complementing the filtration process with some degree of heat treatment.
2. Number of sterilization filters recommended by EU Annex 1 when sterilization is done through filtration method? What should be the location of the filer?
Due to the potential additional risks of the filtration method as compared with other sterilization processes, a second filtration via a further sterilised micro-organism retaining filter, immediately prior to filling, may be advisable. The final sterile filtration should be carried out as close as possible to the filling point.
3. When to perform filter integrity testing and why it is important?
The integrity of the sterilised filter should be verified before use and should be confirmed immediately after use by an appropriate method such as a bubble point, diffusive flow or pressure hold test. The time taken to filter a known volume of bulk solution and the pressure difference to be used across the filter should be determined during validation and any significant differences from this during routine manufacturing should be noted and investigated. Results of these checks should be included in the batch record. The integrity of critical gas and air vent filters should be confirmed after use. The integrity of other filters should be confirmed at appropriate intervals.
4. What is the preferred duration of sterilization filter as per EU Annex 1?
The same filter should not be used for more than one working day unless such use has been validated.
Reference: EudraLex – The Rules Governing Medicinal Products in the European Union Volume 4, EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Annex 1 – Manufacture of Sterile Medicinal Products – 01 March 2009