IVD Metrological traceability without a reference measurement procedure

#1
I am new to IVDs from a background in medical devices and am a little confused how meteorological traceability can work in IVDs when there are no reference measurement procedures for particular analyte in matrix concentrations and how to deal with assigned values which are not lengths and weights.

Let's assume hypothetically that we are an IVD manufacturer which produces an IVD kit for measuring NaCl in serum which requires an assigned value to a calibrator of 10 mg Sodium Chloride (NaCl) per 1 ml serum.

We are fortunate that there exists a reference standard material for Sodium Chloride (NIST Standard Reference Material 919b) with a described reference measurement procedure how this standard reference material was determined to have a known concentration of pure NaCl.

Let's assume further, that unfortunately there seems to be missing a reference measurement procedure for NaCl in serum and thus no reference measurement standard for NaCl in serum can be bought from any reference measurement laboratory or a measurement be ordered as a service. In this hypothetical world only the manufacturers IVD kit itself exists for which we want to create the calibrator.

What shall the IVD manufacturer do in this situation?

Is it allowed to maintain a meteorological traceability by weighting the analyte NaCl (for which we can buy traceable secondary standards) and weighting the matrix serum and manufacturing a calibrator of known concentration NaCl in serum by just mixing those two known quantities? We can verify the concentration then with the IVD kit, but it cannot measure with a higher order measurement procedure.

In other words does ISO 17511 allow any deviation from measurement of a concentration of analyte directly by arguing about how the lower level calibrator was produced by mixing analyte in matrix?
 
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dwperron

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#4
Let's assume further, that unfortunately there seems to be missing a reference measurement procedure for NaCl in serum and thus no reference measurement standard for NaCl in serum can be bought from any reference measurement laboratory or a measurement be ordered as a service. In this hypothetical world only the manufacturers IVD kit itself exists for which we want to create the calibrator.
What shall the IVD manufacturer do in this situation?



Let's just say that I don't want to get involved in dealing with hypothetical equipment and processes.
I find it hard enough dealing with actual problems.
 
#5
Let's just say that I don't want to get involved in dealing with hypothetical equipment and processes.
I find it hard enough dealing with actual problems.
I was hoping this would be easier to understand.

Analyte = Iohexol (e.g. European Pharmacopeia 1141)
Matrix = Human Serum
Manufacturer Method = HPLC-based analysis
 

John Broomfield

Staff member
Super Moderator
#7
European Pharmacopoeia 1141 is an internationally recognized reference standard.

Along with their use of a standard method, labs provide comparable results.

Given these controls what exactly is the problem you want to solve?
 
#8
European Pharmacopoeia 1141 is an internationally recognized reference standard.

Along with their use of a standard method, labs provide comparable results.

Given these controls what exactly is the problem you want to solve?
Dear John,

The challenge is to measure the concentration of the analyte (Iohexol) in a matrix (Serum) for which there isn't a reference measurement procedure.

We can use our own method (3% bias) using our own manufactured calibrants, but there is no higher order measurement method using which we could trace it to the EP 1141.
 

John Broomfield

Staff member
Super Moderator
#9
So, you will have organized inter-laboratory comparison studies (ISO/IEC 17043) and proficiency testing (ISO Guide 43).

Did either or both of these deliver the required degree of confidence?
 
#10
We haven't done this and haven't found any ISO 17043 accredited proficiency testing laboratory which offers our combination of analyte / measurand.

But did I understand you correctly, that this would be one way forward to find somebody accredited to ISO 17043 and let them develop a method or use a method from literature for assessing it? If I look to the offerings of the proficiency laboratories I find only well-established markers/chemicals and not novel markers.
 
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