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Nondestructive Quantitative Inspection of Drug Products Using Benchtop NMR Relaxometry—the Case of NovoMix® 30

A Correction to this article was published on 06 June 2019

This article has been updated


Batch-level inference-based quality control is the standard practice for drug products. However, rare drug product defects may be missed by batch-level statistical sampling, where a subset of vials in a batch is tested quantitatively but destructively. In 2013, a suspension insulin product, NovoLog® Mix 70/30 was recalled due to a manufacturing error, which resulted in insulin strength deviations up to 50% from the labeled value. This study analyzed currently marketed FlexPen® devices by the water proton transverse relaxation rate using a benchtop nuclear magnetic resonance relaxometer. The water proton transverse relaxation rate was found to be sensitive to detecting concentration changes of the FlexPen® product. These findings support the development of vial-level verification-based quality control for drug products where every vial in a batch is inspected quantitatively but nondestructively.

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Change history

  • 06 June 2019

    Typesetting error occurred and author corrections to the equations and text edits at the proofing stage were not incorporated in the published article. The original article has been corrected.



Nuclear magnetic resonance

T 2 :

Transverse relaxation time

R 2 :

Transverse relaxation rate


Quality control


Drug product


Drug substance


Number of scans


Relaxation delay




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Funding Source

K.T.B. received an M-CERSI Postdoctoral Fellowship from the FDA. A part of the work was supported by the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL). The University of Maryland Baltimore provided additional funding.

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Correspondence to Y. Bruce Yu.

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K.T. Briggs, M.B. Taraban, and Y.B. Yu are co-inventors on issued and pending patents on wNMR technologies.

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This article does not contain any studies with human or animal subjects.

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Key Points

• Low-field benchtop NMR relaxometry is capable to detect drug dose deviations in intact drug products by measuring the water proton transverse relaxation rate.

• Measuring the water proton relaxation rate of a drug product is a nondestructive method that has the potential to serve as a quality control method for released drug products.

• Prime candidates for nondestructive verification-based quality control are scenarios where the occurrence of drug product defects is low, but the consequences of a defect are serious.

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Briggs, K.T., Taraban, M.B., Wang, W. et al. Nondestructive Quantitative Inspection of Drug Products Using Benchtop NMR Relaxometry—the Case of NovoMix® 30. AAPS PharmSciTech 20, 189 (2019).

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  • NMR
  • insulin
  • quality control
  • nondestructive inspection
  • adverse events