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. 2019 Jan;13(1):55-59.
doi: 10.1177/1932296818783783. Epub 2018 Jun 28.

Concentrations of Intact Insulin Concurs With FDA and EMA Standards When Measured by HPLC in Different Parts of the Distribution Cold Chain

Alan Moses  1 , Jesper Bjerrum  2 , Morten Hach  2 , Lars Holm Wæhrens  2 , Anders Dyhr Toft  2
Affiliations

Concentrations of Intact Insulin Concurs With FDA and EMA Standards When Measured by HPLC in Different Parts of the Distribution Cold Chain

Alan Moses et al. J Diabetes Sci Technol. 2019 Jan.

Abstract

Background: The article by Carter and Heinemann raised serious concerns about the concentrations of insulin in vials being sold in US pharmacies. To study the claims made in the manuscript, we reviewed Novo Nordisk data on insulin concentration.

Methods: Insulin concentrations within vials from three different sources along the distribution chain were evaluated utilizing currently accepted US Pharmacopeia methodology: (1) insulin content and stability based on production batches covering 7 years of insulin production, (2) insulin content in samples returned to Novo Nordisk over the last three years in the United States, and (3) data from eight years of independent EMA testing.

Results: The data demonstrated that without exception (1) insulin quality based on stability data was maintained, even in scenarios that stressed the normal recommendations for temperature storage conditions, (2) insulin content from the last three years of samples returned to Novo Nordisk from patients in the United States (233 vials) was within USP requirements recognized by FDA, and (3) ten years of independent EMA sampling of products obtained at wholesalers and pharmacies across the EU confirmed compliance (n = 43).

Conclusions: The study by Carter and Heinemann utilized an LC-MS technique, which has not been validated for the quantification of insulin in pharmaceutical preparations. It appears likely that their findings are the result of the method utilized and not due to decreased insulin content in samples. However, recognizing the importance of maintaining Insulin content from production to the patient, Novo Nordisk supports continued evaluation of insulin distributed to pharmacies and patients utilizing validated techniques compliant with international pharmacopeias.

Keywords: RP-HPLC; insulin content; quality assurance.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Alan Moses, Jesper Bjerrum, Morten Hach, Lars Holm Wæhrens, Anders Dyhr Toft are full-time employees and minor stockholders of Novo Nordisk.

References

    1. Sarbacker GB, Urteaga EM. Adherence to insulin therapy. Diabetes Spectr. 2016;29(3):166-170. - PMC - PubMed
    1. Carter AW, Heinemann L. Insulin concentration in vials randomly purchased in pharmacies in the united states: considerable loss in the cold supply chain. J Diabetes Sci Technol. 2018;12(4):839-841. - PMC - PubMed
    1. US Pharmacopeia. Insulin Human Drug Products 100 IU/ml. Rockville, MD: US Pharmacopeia; 2016.
    1. American Diabetes Association. Insulin concentration concerns: a message from William T. Cefalu, MD. Diabetes Stops Here. January 22, 2018.
    1. European Pharmacopoeia Commission. Council of European Directorate for the Quality of Medicines (EDQM). 9th ed. Insulin Human Drug Products 100 IU/ml.

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