AAPS PharmSciTech

, Volume 13, Issue 3, pp 911–918

On the Shelf Life of Pharmaceutical Products

  • Robert Capen
  • David Christopher
  • Patrick Forenzo
  • Charles Ireland
  • Oscar Liu
  • Svetlana Lyapustina
  • John O’Neill
  • Nate Patterson
  • Michelle Quinlan
  • Dennis Sandell
  • James Schwenke
  • Walter Stroup
  • Terrence Tougas
Research Article

Abstract

This article proposes new terminology that distinguishes between different concepts involved in the discussion of the shelf life of pharmaceutical products. Such comprehensive and common language is currently lacking from various guidelines, which confuses implementation and impedes comparisons of different methodologies. The five new terms that are necessary for a coherent discussion of shelf life are: true shelf life, estimated shelf life, supported shelf life, maximum shelf life, and labeled shelf life. These concepts are already in use, but not named as such. The article discusses various levels of “product” on which different stakeholders tend to focus (e.g., a single-dosage unit, a batch, a production process, etc.). The article also highlights a key missing element in the discussion of shelf life—a Quality Statement, which defines the quality standard for all key stakeholders. Arguments are presented that for regulatory and statistical reasons the true product shelf life should be defined in terms of a suitably small quantile (e.g., fifth) of the distribution of batch shelf lives. The choice of quantile translates to an upper bound on the probability that a randomly selected batch will be nonconforming when tested at the storage time defined by the labeled shelf life. For this strategy, a random-batch model is required. This approach, unlike a fixed-batch model, allows estimation of both within- and between-batch variability, and allows inferences to be made about the entire production process. This work was conducted by the Stability Shelf Life Working Group of the Product Quality Research Institute.

KEY WORDS

ICH method quantile for distribution of batch shelf lives random-batch model shelf life terminology stability 

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Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Robert Capen
    • 1
    • 13
  • David Christopher
    • 1
  • Patrick Forenzo
    • 2
  • Charles Ireland
    • 3
  • Oscar Liu
    • 4
  • Svetlana Lyapustina
    • 5
  • John O’Neill
    • 6
  • Nate Patterson
    • 7
  • Michelle Quinlan
    • 8
  • Dennis Sandell
    • 9
  • James Schwenke
    • 10
  • Walter Stroup
    • 11
  • Terrence Tougas
    • 12
  1. 1.Nonclinical and Pharmaceutical Sciences Statistics, MerckWest PointUSA
  2. 2.PDU4 Team, NovartisEast HanoverUSA
  3. 3.Regulatory AffairsColgate PalmolivePiscatawayUSA
  4. 4.Pharmaceutical Sciences and Clinical Supplies, MerckSummitUSA
  5. 5.Pharmaceutical Practice Group, Drinker Biddle & ReathWashingtonUSA
  6. 6.Corporate QualityBoston ScientificNatickUSA
  7. 7.Inspiration BiopharmaceuticalsLaguna NiguelUSA
  8. 8.Clinical Pharmacology BiostatisticsNovartis OncologyFlorham ParkUSA
  9. 9.S5 ConsultingLundSweden
  10. 10.Applied Research ConsultantsNew MilfordUSA
  11. 11.StatisticsUniversity of Nebraska-LincolnLincolnUSA
  12. 12.Analytical DevelopmentBoehringer IngelheimRidgefieldUSA
  13. 13.Merck & Co. Inc.West PointUSA

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