Question: What is the acceptable media fill frequency in relation to the number of shifts? Normally, media fills should be repeated twice per shift per line per year. Is the same frequency expected of a process conducted in an isolator?
According to FDA's principles, the frequency of media fills should be fixed in relation to the shifts on the basis of a risk assessment. In traditional aseptic filling, one media fill per shift per half year is expected. On a line with 2 shifts, this requires at least 4 media fill runs. For a closed and highly automated system over several shifts, however, the number of media fill runs can be reduced in case of a rigorous media fill design. Isolators and closed-vial filling are expressly mentioned as closed systems; but RABS (Restricted Access Barrier System) are expressly excepted from this group. A semi-annual media fill per line is still expected; however, the absolute number of media fill runs can be reduced based on a sound risk rationale under certain circumstances. Here you can read the FDA's answer.
Dr Andreas Mangel
On behalf of the European Compliance Academy (ECA)
Source: FDA Webpage, Questions and Answers on Current Good Manufacturing Practices, Good Guidance Practices, Level 2