Medical device manufacturer, Roche, has issued a medical device safety alert concerning its ONLINE TDM Vancomycin Gen.3. The affected products are identified as follow:

• Product Name: ONLINE TDM Vancomycin Gen.3 (VANC3)
• System: A) cobas c 311 analyzer; B) cobas c 501/502 modules; C) cobas c 701/702 modules; D) cobas c 503 analytical unit
• Part Number: A) & B) 06779336190, 06779344190; C) 06781632190; D) 08445605190, 08058849190

The manufacturer has received a small number of reports about incorrectly low results for vancomycin in individual patient samples measured with the ONLINE TDM Vancomycin Gen.3 assay on cobas c platforms (VANC3).

Some results were flagged as below the measuring range (< Test; defined by Limit of Quantification (LoQ) 4.0μg/mL). As the patients were receiving vancomycin pharmacotherapy, the results below the measuring range were unexpected and thus implausible. Other results were erroneously low within the measuring range without any flag. Internal investigations using alternative reagent formats and techniques (e.g. LC-MS/MS) confirmed that these samples contained vancomycin and therefore the results obtained with the affected products were incorrect.

According to the manufacturer, the VANC3 immunoassay uses a competitive assay format in which microparticles agglutinate. In the reported cases the VANC3 reagent reaction kinetic is impaired. The kinetics of the affected samples showed an unusual strong agglutination of the microparticles. This led to the incorrect results below the measuring range (<4.0μg/mL) observed in the reported cases. With the competitive test format of VANC3 a lower aggregation kinetic would be expected for samples containing vancomycin.

From the reaction kinetics of the incorrectly low results within the measuring range (4.0-80μg/mL) it is concluded that the affected patient samples contain one or more non-specific interfering substance(s) that enhance the agglutination. Despite several investigations, the interfering substance(s) could not be isolated. Immunofixation was performed on the available samples and a suspicious immunoglobulin pattern was observed. The exact target/epitope of these immunoglobulins could not be determined.

For results below the measuring range, detection is probable, as this scenario is implausible and not expected during vancomycin pharmacotherapy. For incorrectly low results within the measuring range detection may be unreliable or difficult. Incorrectly low VANC3 test results within the measuring range are difficult to detect if not confirmed by an alternative method. The frequency of occurrence is remote based on the reported cases per number of tests performed.

The manufacturer Roche will implement a'prozone check'for the VANC3 applications ACN (8)159 for the cobas c 311 analyzer, c 501/502 and c 701/702 modules. This check detects samples with a stronger agglutination than that of a vancomycin-free sample or the zero calibrator. Such affected samples will be flagged with a">Kin"flag. For the VANC3 application (ACN 21210) on cobas c 503 analytical unit a corresponding check (kinetic unstable check) has already been implemented with the launch version. The affected samples will be flagged with ">Kin3".

The Instructions for Use (IFU) will be updated to include the following information and disclaimer:

• "A test result flagged with ">Kin", ">Kin3" indicates unusual reaction kinetics. There is a high probability that the sample contains an interfering substance which accelerates the reaction kinetics. For such very rare samples it is not possible to report a reliable analyte concentration with this assay."
• "In very rare cases (less than 1 reported case per 1 000 000 tests) certain immunoglobulins can unspecifically interfere with the agglutination reaction leading to unreliable results."

Affected customers are asked to take the following actions:

• Download the updated VANC3-application to implement the prozone check settings.
• Samples showing incorrectly low VANC3 test results below and within the measuring range should be re-tested with alternative immunoassays or LC-MS/MS

According to the local supplier, the affected products are distributed in Hong Kong.

If you are in possession of the products, please contact your supplier for necessary actions.

Posted on 19 July 2019