USP<645> Water Conductivity – Always Making Waves. Are You Drowning Trying to Interpret This Regulation?
Are You Drowning Trying to Interpret USP<645>?
If the answer to the above question is yes – then let me reassure you, you are not alone! I am the Sales Manager for the Analytical Team in Masons with a background in Bioanalysis. In my line of work I have the privilege of working with numerous different sectors within the science community including food & beverage, medical device, academia, government bodies and pharma. Ireland in my opinion, is one of the most regulated countries in the EU especially in the pharmaceutical sector – and rightly so!
However, we are probably one of the best countries in the world at adhering to these regulations, and in some cases overcompensate the requirements to be the “best of the best”. As a result, I often see our customers struggling to meet what they have interpreted to be correct, in an effort “to be sure to be sure” and pass every audit thrown at them. One such regulation that has caused the most upheaval in the pharma world that I have seen of late is USP<645> Water Conductivity. In just one short paragraph of this monograph I have seen utter confusion, stress, frustration and investigations to last me a lifetime!
So I’m here to try set the record straight based on my 22 years of experience in the business, my direct correspondence with the USP themselves and advice from our trusted supplier Mettler Toledo.
Under the paragraph title cell constant otherwise known as the cc, the USP<645> states that you must have a cell constant known within +/-2% ( ref: USP42-NF37-645-Conductivity). This means you are required to use a certified cc that has been certified within +/-2%. Mettler Toledo provide the InLab741 conductivity sensor with a measuring range of 0.001uS/cm to 500uS/cm complete with a certified cell constant certified to +/-2%.
The cell constant paragraph in USP<645> continues on to describe how you can verify your cell constant, and if necessary, how you can adjust. It is from this point on the most common misconception arises across the industry. Most companies interpret this as they have to adjust their new probe, thereby creating a new cc – which in turn must be within +/-2% of the certified cc. If this sounds familiar and this is how you are interpreting this section of USP<645> then fortunately or unfortunately depending on how you see it, this is a misinterpretation.
I’ve recently had to do a lot of work for a couple of my customers whom were running into trouble with this. I contacted our supplier Mettler Toledo as well as contacting the USP to check my facts. So here it is folks, this is it from the horse’s mouth so to speak.
A response from my USP colleagues themselves. It doesn’t change. It’s a factor essentially within a measuring range of the sensor that is created. This “number” i.e. cell constant is then used in logarithm of the instrument to produce your conductivity results. For want of a better way of describing it – it’s similar to your density factor on a density meter. It remains constant until you create a new one.
The Mettler Toledo InLab741 has a certified cc to +/-2%, so you do not need to create a new cc. The new Seven Excellence Mettler Toledo meters will automatically recognise the sensor and import your cell constant. Meaning you can get on with a simple verification. It is perfectly acceptable to enter your certified cc into your meter as mode of calibration.
It is what it is. Think of it like a balance, when you are calibrating a balance you are telling it what each weight looks like for example when performing a linearity adjustment you put the weight on and register it as that weight i.e. 50g, 100g, etc. You have no idea if that adjustment has failed or passed until you perform a verification. At which stage you will put the weights back on and compare the displayed value to true – applying your pass/fail criteria.
The certified cc once imported or entered into the meter can be verified using a known standard. In Mettler Toledo’s case we use their recommended procedure of verifying with 84uS/cm or 10uS/cm. Verification is performed by reading the standard and comparing it’s value to that of the standard tables or cert of analysis. It’s at this point we can apply a verification tolerance of +/-2%.
Finally, if for any reason during the lifetime of your sensor you need to create a new cc, then you do so with known standards following the recommended procedure of the manufacturer. Mettler Toledo have a whitepaper “Perform Conductivity Measurements” which I am sharing here with you will give you these easy steps to follow. Again, I can’t say this enough! The new cell constant is not required to be within +/-2% of the certified cc. How can it? Think about it, it’s a constant, the certified cc was factory produced in best conditions, you are creating a new cc in your environment with your own batch of buffers. So believe me when I tell you if you apply the misconception I mentioned at the start, this is point you will see a fail.
Lastly, as I mentioned before, it is the verification of the new cc that you apply your tolerance at which stage when it is in use I would advise a tolerance of +/-5% in accordance with the final paragraph of USP<645> under system verification.
Of course I could talk allot more about conductivity, temperature affects, and further implications of USP<645> but for now I think if we can agree to get this bit right it would make life easier for everyone and hopefully stop us all from drowning in regulation USP<645>!
Sharon Somers is a Sales Manager for the Analytical Team at Mason Technology.
Sharon has extensive experience in advising our customers within several market sectors, including pharmaceutical and medical device, on ensuring compliance with all risk management and regulatory requirements within their sector. Sharon holds a National Diploma in Bioanalysis and a BA (Hons) in Business Studies with Psychology.
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