No surprise that Instructions For Use (package inserts) are weak



A recent letter in Clinical Chemistry (subscription required) talks about package inserts from manufacturers (also called instructions for use (IFU). The letter says that manufacturers’ IFUs often do not follow CLSI guidelines with respect to hemoglobin interference.

This should come as no surprise – here’s why.

The authors cite FDA regulations which state: “Limitation of the procedure: Include a statement of limitations of the procedure. State known extrinsic factors or interfering substances affecting results.”

This regulation leaves a lot of leeway as to what should appear in the IFU.

So the authors say that CLSI guidelines (C56 and EP7) are not followed. One should understand that CLSI guidelines are not regulations. No manufacturer has to follow them. Moreover, these guidelines are often manufacturer friendly as manufacturers dominate the committees who prepare the documents. For example, the authors cite C56 which has an example for how to report when there is no hemoglobin interference for glucose. The table contains the concentration of hemoglobin tested, two glucose levels, and bias < 10%.

This is messed up! If bias found were 9%, this CLSI guideline is suggesting that it is ok to say there was no bias!

So even if manufacturers followed CLSI guidelines, maybe this wouldn’t be so good.

To understand why a CLSI document would permit the claim “no bias” when 9% bias was found…

CLSI prides itself on equal influence of “professions” (e.g., clinical chemists in hospitals), “government” (e.g., FDA), and “manufacturers” (people in industry). But the industry people are largely from regulatory affairs and their role on committees has often been an obstructionist role. Basically, the industry – like industries in other fields – does not want to be regulated at all, so if there has to be a standard, the regulatory people try to make it as industry friendly as possible.

As an example of the obstructionist role, consider EP7. It was initially published as a “P” (proposed) version in 1986. Only “A” (accepted) versions are accepted by the FDA. So how long did it take for this standard to go from P to A: 16 years! (initially published in 2002.) It wasn’t until I was the chair of the Evaluation Protocol Committee that this project got moving faster than a snail’s pace and was finished.

And then there was the CLS standard EP11 – Uniformity of Claims. It was intended to be a guideline for IFUs. It’s hard to say if this standard would help since it could also be ignored. It was published as a “P” document in 1996. CLSI management (who was pressured by industry) pressured me to cancel it – I didn’t but they did and it was not advanced and is no longer available.

Finally, I can’t speak about other companies, but in the company that I worked for, IFUs were prepared by the marketing department.


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