10/11 March 2020
The installation of pipework leads to recurrent discussions about how dead legs can be prevented and about the maximum length outgoing pipes/pipe tees may have for the sensor. There is less throughflow in dead legs. Hence, it is harder to clean them and during thermal sanitisation it takes longer until these "branches" have also reached the required temperature. In calls for tender and tests the 3D/6D rule is often used for the specification, but not always in the completely correct way. In order to further explain this, please read following the history of this rule.
The rule for the prevention of dead legs (in a WFI system) is mentioned for the first time in the draft of the FDA Guides for Large Volume Parenterals (LVP), 21 CFR 212.49 in 1972. This requirement was taken up in the FDA Guide to Inspections of high purity water systems in 1993 - only now it was called 6D rule. This document is still used by FDA inspectors as guidance for GMP inspections. In 2001 the dead leg rule reappeared in an ISPE guide. The ISPE Baseline Guide Water and Steam now talks about the 3D rule. Further statements can be found in WHO TRS 929 (1,5 D), WHO TRS 970 (3D) and in ASME BPE-2009 (2D). This is a standard of the American Society of Mechanical Engineers for BioProcessing Equipment. This means:
But how does it work in practice? Is one rule more binding or better than the others?
One has to know that the 3D and the 6D rule cannot be compared directly because they have a different reference point. In the case of the 3D rule the length L of the dead leg is measured from the pipe wall of the main pipe and put in relation to the diameter of the parting pipe. The initial 6D rule measures the length L beginning in the centre of the main pipe.
As a rule the "3D or shorter" has proven itself for water systems and is said to be state of the art. But the following is also valid: The higher the risk or the value of the product the shorter. Today 1.5 D is state of the art in the case of biotechnology applications. But this may also mean that a piece of pipe in an older clean steam system may remain 6D without posing a GMP risk.