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Impact of Pharmacometric Analyses on New Drug Approval and Labelling Decisions

A Review of 198 Submissions Between 2000 and 2008

Abstract

Pharmacometric analyses have become an increasingly important component of New Drug Application (NDA) and Biological License Application (BLA) submissions to the US FDA to support drug approval, labelling and trial design decisions. Pharmacometrics is defined as a science that quantifies drug, disease and trial information to aid drug development, therapeutic decisions and/or regulatory decisions. In this report, we present the results of a survey evaluating the impact of pharmacometric analyses on regulatory decisions for 198 submissions during the period from 2000 to 2008. Pharmacometric review of NDAs included independent, quantitative analyses by FDA pharmacometricians, even when such analysis was not conducted by the sponsor, as well as evaluation of the sponsor’s report. During 2000–2008, the number of reviews with pharmacometric analyses increased dramatically and the number of reviews with an impact on approval and labelling also increased in a similar fashion. We also present the impact of pharmacometric analyses on selection of paediatric dosing regimens, approval of regimens that had not been directly studied in clinical trials and provision of evidence of effectiveness to support a single pivotal trial. Case studies are presented to better illustrate the role of pharmacometric analyses in regulatory decision making.

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References

  1. 1.

    Office of Clinical Pharmacology, US FDA Center for Drug Evaluation and Research. Manual of policies and procedures: an integrated genomics, pharmacometrics, and clinical pharmacology review process [document reference MAPP 5100.5; online]. Available from URL: http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/UCM215862.pdf [Accessed 2011 Jul 25]

  2. 2.

    Bhattaram VA, Booth BP, Ramchandani RP, et al. Impact of pharmacometrics on drug approval and labeling decisions: a survey of 42 new drug applications. AAPS J 2005; 7: E503–12

  3. 3.

    Bhattaram VA, Bonapace C, Chilukuri DM, et al. Impact of pharmacometric reviews on new drug approval and labeling decisions: a survey of 31 new drug applications submitted between 2005 and 2006. Clin Pharmacol Ther 2007; 81: 213–21

  4. 4.

    US FDA. Drug approval package: Ilaris® (canakinumab) [FDA application no. (BLA) 125319; online]. Available from URL: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist [Accessed 2011 Jul 25]

  5. 5.

    US FDA. Drug approval package: Cleviprex® (clevidipine butyrate) [FDA application no. (NDA) 022156; online]. Available from URL: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist [Accessed 2011 Jul 25]

  6. 6.

    US FDA. Drug approval package: Lamictal® XR (lamotrigine) [FDA application no. (NDA) 022115; online]. Available from URL: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist [Accessed 2011 Jul 25]

  7. 7.

    Booth BP, Rahman A, Dagher R, et al. Population pharmacokinetic-based dosing of intravenous busulfan in pediatric patients. J Clin Pharmacol 2007; 47: 101–11

  8. 8.

    Li F, Nandy P, Chien S, et al. Pharmacometrics-based dose selection of levofloxacin as a treatment for post-exposure inhalational anthrax in children. Antimicrob Agents Chemother 2010; 54: 375–9

  9. 9.

    Madabushi R, Cox DS, Hossain M, et al. Pharmacokinetic and pharmacodynamic basis for effective argatroban dosing in pediatrics. J Clin Pharmacol 2011; 51: 19–28

  10. 10.

    Tornoe CW, Tworzyanski JJ, Imoisili MA, et al. Optimising piperacillin/tazobactam dosing in paediatrics. Int J Antimicrob Agents 2007; 30: 320–4

  11. 11.

    US FDA. FDA pharmacometrics 2020 strategic goals [online]. Available from URL: http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm167032.htm#FDAPharmacometrics2020StrategicGoals [Accessed 2011 Jul 25]

Download references

Acknowledgements

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the official views of the FDA.

No sources of funding were used in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Correspondence to Dr Joo Yeon Lee.

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Lee, J.Y., Garnett, C.E., Gobburu, J.V.S. et al. Impact of Pharmacometric Analyses on New Drug Approval and Labelling Decisions. Clin Pharmacokinet 50, 627–635 (2011). https://doi.org/10.2165/11593210-000000000-00000

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Keywords

  • Lamotrigine
  • Regulatory Decision
  • Canakinumab
  • Clevidipine
  • Regulatory Question