In the past I had designed a simplified designation for referring to the values for cleaning validation limits in different situations. This system (including L0, L1, L2, L3, L4a, L4b and L4c) was originally formulated around 2004 and then updated and refined in a Cleaning Memo of September 2012. Not surprisingly (!!!) I like the system a lot. Rather than using phrases like Acceptable Residue Level (ARL) and Maximum Allowable Carryover (MAC) which are used differently, and in some cases in a rather overly broad way, by different companies, the proposed system attempted to use terms with no “cognitive” value and no unneeded associations, to refer to limits in this manner:
L0: The safe amount of residue that can be taken daily for a prolonged period
L1: The safe concentration of residue in the next manufactured product
L2: The total amount of residue allowed in a batch of the next product
L3: The amount of residue allowed per surface area for product contact surfaces
L4a: The amount of residue per swab (for swab sampling)
L4b: The concentration of residue in the liquid the swab is extracted into
L4c: The concentration of residue in the liquid in the rinse sample
For those who have adopted this “language” (and it is just a language change which requires no fundamental change in how limits are calculated; it is just a change in how those limits are referred to), it has helped those companies more precisely and consistently to describe what they are doing. The system is one used in the eResidue cleaning validation software program. The system is also used in the recent Indian Pharmaceutical Alliance (IPA) cleaning validation guidance (although that guidance omits L0 and L4b).
Despite the usefulness of that system, I have noticed a “hole” in its application as I tried to refer to data measured in a protocol. Here is an example of this “hole”. Suppose I calculate the limit in the extracted swab solution; in this “L” system, the L4b is the value of the limit in the extracted swab solution. After my L4b limit is set, I then wanted to measure the residue values for swab sample location XYZ. What do I call the measured value? Well, strictly speaking is not L4b, since L4b is the concentration limit that I want to not exceed. Therefore, I have typically tried (but not always succeeded) to refer to the measured residue value in that swab sample as “measured L4b for sample location XYZ”. That is cumbersome, and is particularly so if I want that for a title atop a column of entered data summarizing results in a protocol report.
So, because I am sometimes lazy (and even though I get paid as a consultant by the number of words I generate), I wanted a simpler system. Here is what I now propose, which is essentially substituting the letter M for the letter L that was used in the system for limits. M here refers to the “measured value” for a specific sample or situation. So, here is the system:
M0: Equivalent daily amount potentially taken based on the measured sample analytical value
M1: Equivalent residue concentration in the next batch based on the measured sample analytical value
M2: Equivalent total amount of residue per batch based on the measured sample analytical value
M3: Equivalent amount of residue per surface area based on the measured sample analytical value
M4a: Measured amount (per swab) for a specific swabbed location
M4b: Measured concentration in swab extraction liquid for a specific swabbed location
M4c: Measured concentration in the rinse liquid for a specific rinse sample
In each case, the M value refers to the measured value (or equivalent value calculated based on the measured analytical result for a specific sample). While the L values (the limits) are typically the same for a given protocol, the M values (based on the analytical value measured for a specific sample) will more typically vary.
Note that most commonly only the M4a, M4b and M4c will be used. In some cases, such as in stratified sampling (see the Cleaning Memo of March 2010), M2 will be appropriate. Rarely will the other M terms be used.
If you like this system, do not change your program if this terminology is the only change. However, as you make other significant changes to your program, this may be something to consider. However, also realize that any change to your top level documents will also require changes to a myriad of other associated documents. Also, this M system does not replace the L system; it merely supplements it.