sterilizing filters should be as close to the point of fill as possible

2024-08-27 Eternalwater

This case comes from an experience of participating in the education of the International Pharmaceutical Engineering Management (IPEM) course. A student asked the teacher Lan a question. The general situation is as follows:

A company wanted to export to the European Union and applied for EU GMP certification. But The inspector proposed that the sterilizing filter is a little bit far away from the filling room and asked the company to put the sterilizing filter in the filling room. However, the company worried that PUPSIT integrity test requested for sterilizing filtration will introduce water and gas into the B-level area. On the one hand, they were concerned about the aseptic risks , and on the other hand, the reformation is too much. The purpose of the PUPSIT test is to detect whether there is minor incompleteness in the sterilized filter.

Here's my question: Which of the two images below is more in alignment with "sterilizing filters should be as close to the point of fill as possible "?

Before that, let’s look at the regulatory requirements. The original text in the EU Appendix "Due to the potential additional risks of a sterile filtration process, an additional filtration through a sterile sterilising grade filer, as closed to the point of fill as possible, should be considered as part of an overall CCS."

GMP Appendix 1 Article 75 Filtration and sterilization of non-final sterilized products shall meet the following requirements: (2) Measures shall be taken to reduce the risk of filtration and sterilization. It is advisable to install a second sterilized sterilizing filter to filter the liquid again, and the final sterilizing filter should be as close to the point of fill as possible.
Question: Is the proximity to the point of fill here physical proximity?

Let's take a look at Lan's explanation again. He said that "closed" does not mean physical proximity, but more refers to the need to minimize pipeline connections or use aseptic connections after sterilizing filtration. If it is an aseptic connection, a longer pipe can also be regarded as "closed". He believed that the inspector in the student's question may not be a native speaker of English, or may not have received enough training to correctly understand this sentence.

I personally agree with Lan's explanation, so the first one in the first image can reduce the aseptic risks more. When designing processes, companies should try to reduce pipeline connections or change them to aseptic connections, and do not only consider the proximity in distance.

Statement 1. The cases in this public account are all fictitious by the author, or have been fully reprocessed, and the values quoted are not actual values. If it still causes troubles to some companies, please contact us for deletion. 2. The articles published on this public account are all intended to promote exchanges and learning among colleagues in the pharmaceutical industry. Not for any commercial use.

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