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In vitro Approaches to Support Bioequivalence and Substitutability of Generic Proton Pump Inhibitors via Nasogastric Tube Administration

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Abstract

Administration of proton pump inhibitors (PPIs) through nasogastric tubes may present risks. If the PPI drug products are not prepared properly, clogging or obstruction of nasogastric tubes can pose a safety concern. In addition, the integrity of the enteric coating of the drug product may be damaged resulting in reduced bioavailability of the active moiety. From the perspective of administration of generic PPIs when compared to the reference drug product, differences in formulation can potentially result in a greater relative risk for the generic drug product. As part of the assessment of bioequivalence, the Office of Generic Drugs (OGD) has developed a suite of in vitro testing to compare the delivery of the generic and reference products via nasogastric tubes. These in vitro tests assess essential attributes associated with the likelihood of clogging and maintenance of the enteric coating. These in vitro tests include studies evaluating sedimentation, granule size distribution, drug recovery, and acid resistance. One of the challenges is that while the administration of PPIs through nasogastric tubes is common in clinical practice, this issue is not uniformly addressed in the FDA approved label of the reference drug products. This paper discusses the design and rationale for in vitro testing of PPI formulations with respect to bioequivalence via nasogastric tube administration and in addition, it summarizes commonly occurring deficiencies in the in vitro nasogastric tube testing of 14 recent Abbreviated New Drug Applications (ANDA) submitted for five generic PPI drug products.

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Author notes

  1. Ping Ren and Minglei Cui contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Ping Ren, Dajun Sun & Wenlei Jiang

  2. Office of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire, Silver Spring, Maryland, 20993, USA

    Minglei Cui, Li Xia, Trueman Sharp, Dale P. Conner, John Peters, Ethan Stier & Xiaojian Jiang

  3. Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Om Anand & Zhuojun J. Zhao

Authors
  1. Ping Ren
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  2. Minglei Cui
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  4. Li Xia
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Correspondence to Xiaojian Jiang.

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The views expressed in this article are those of the authors and do not reflect the official policy of the FDA. No official support or endorsement by the FDA is intended or should be inferred.

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Ren, P., Cui, M., Anand, O. et al. In vitro Approaches to Support Bioequivalence and Substitutability of Generic Proton Pump Inhibitors via Nasogastric Tube Administration. AAPS J 19, 1593–1599 (2017). https://doi.org/10.1208/s12248-017-0137-x

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  • DOI: https://doi.org/10.1208/s12248-017-0137-x

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