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Canadian Journal of Cardiology

Recall of N-Nitrosodimethylamine–Contaminated Pseudogeneric Valsartan: Best Generics Finally No Better Than Others?

Published:August 10, 2018DOI:https://doi.org/10.1016/j.cjca.2018.08.011
      To the Editor:
      Millions of patients worldwide who are treated with valsartan recently received recall notices; their valsartan was found to be contaminated by an impurity—N-Nitrosodimethylamine (NDMA)—known to be a probable human carcinogen.
      Health Canada
      Several drugs containing valsartan being recalled due to contamination with a potential carcinogen; 2018.
      Targeted manufacturers in Canada are all generics manufacturers. Brand-name valsartan and some other generic manufacturers are not affected by this recall, as the active ingredient (ie, valsartan) was supplied from a different source. The presence of this impurity is thought to be related to changes in the way the active substance was manufactured since 2012. The impurity was found incidentally while performing tests other than routine batch-release specification assessments. This incident inevitably reminds us of the 2008 China milk scandal, when tens of thousands babies got sick after drinking melamine-contaminated milk, a toxic industrial compound.
      • Ramzy A.
      • Yang L.
      Tainted baby milk scandal in China; 2018.
      Generic drugs are widely used worldwide to decrease pharmaceutical expenditures for patients and payers. Between a given generic and its corresponding brand-name drug, the strength of the active ingredient, the galenic form, the route of administration, and the indication must be identical. However, inactive ingredients may differ greatly. To ensure pharmacokinetic similarity between generics and the brand-name counterpart, most generics will undergo comparative bioavailability studies in humans before being licensed. There is an exception to every rule: pseudogenerics.
      Pseudogenerics are known to be “exact copies” of the brand-name drug; their composition is exactly the same (active and inactive ingredients) and sometimes referred to as “best” generics. Therefore, health authorities do not require in vivo comparative bioavailability tests to license pseudogenerics, as normally demonstrated in respective product monographs. The actual recall of NDMA-contaminated generic valsartan affects 2 pseudogenerics: in Canada, Sandoz Valsartan (Sandoz Canada Inc, A Novartis Division, Montréal, QC) and valsartan from Pro Doc (Pro Doc, Laval, QC).
      Health Canada
      Several drugs containing valsartan being recalled due to contamination with a potential carcinogen; 2018.
      This situation exposes to daylight that pseudogenerics were containing an active ingredient that has never been tested in humans. Worse, even with strict and well-known good manufacturing practices worldwide, this active ingredient contained an impurity.
      This recall reveals potential serious concern for patient safety and raises a call for action. Manufacturers and policy makers should be fully transparent and answer these questions: (1) Why has this impurity never been detected through routine tests, as per good manufacturing practices? (2) How many patients have been exposed to NDMA-contaminated valsartan? (3) Who is going to fund and perform short- to long-term surveillance studies of these patients?

      Acknowledgements

      The author thanks Dr Paul Poirier for his revision of this article.

      Disclosures

      The author has no conflict of interest to disclose.

      References

        • Health Canada
        Several drugs containing valsartan being recalled due to contamination with a potential carcinogen; 2018.
        (Available at:) (Accessed July 15, 2018)
        • European Medicine Agency
        Update on review of recalled valsartan medicines; 2018.
        (Available at:) (Accessed August 6, 2018)
        • Ramzy A.
        • Yang L.
        Tainted baby milk scandal in China; 2018.
        (Available at:) (Accessed July 24, 2018)
        • Health Canada
        Guidance document. Comparative Bioavailability Standards: Formulations Used for Systemic Effects; 2018.
        (Available at:) (Accessed July 24, 2018)