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Research ArticleTechnology/Application

The Implications of Chromatographically Screening Medical Products for Organic Leachables Down to the Analytical Evaluation Threshold Adjusted for Response Factor Variation

Dennis Jenke and Ted Heise
PDA Journal of Pharmaceutical Science and Technology May 2021, 75 (3) 273-288; DOI: https://doi.org/10.5731/pdajpst.2020.012013
Dennis Jenke
1Triad Scientific Solutions, LLC, Hawthorn Woods, IL; and
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  • For correspondence: dennisjenke@triadscientificsolutions.com
Ted Heise
2MED Institute Inc, West Lafayette, IN
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  • Article
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References

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    Product Quality Research Institute. Safety Thresholds and Best Practices for Extractables and Leachables In Orally Inhaled and Nasal Drug Products, 2006. PQRI Web site. http://pqri.org/wp-content/uploads/2015/08/pdf/LE_Recommendations_to_FDA_09-29-06.pdf (accessed March 7, 2021).
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    International Organization for Standardization, ISO/TS 21726:2019 Biological Evaluation of Medical Devices—Application of the Threshold of Toxicological Concern (TTC) for Assessing Biocompatibility of Medical Device Constituents. ISO: Geneva, 2019.
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    The Analytical Evaluation Threshold (AET), 2005. PQRI Web site. http://pqri.org/wp-content/uploads/2015/08/pdf/PQRI_AET_Poster.pdf (accessed March 7, 2021).
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    The Analytical Evaluation Threshold (AET) Concept, Sensitivity and Analytical Uncertainty. Presented at the Smithers Rapra Leachables and Extractables 2008 Conference, Dublin, Ireland, March 5–6, 2008.
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    Utilization of Internal Standard Response Factors to Estimate the Concentration of Organic Compounds Leached from Pharmaceutical Packaging Systems and Application of Such Estimated Concentrations to Safety Assessment. J. Chromatogr. Sci. 2012, 50 (3), 206–212.
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    Identifying and Mitigating Errors in Screening for Organic Extractables and Leachables: Part 2—The Errors of Inexact Identification and Inaccurate Quantitation. PDA J. Pharm. Sci. Technol. 2020, 74 (1), 108–133.
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    1. Jenke D.,
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    Chromatographic Considerations in the Standardization of Liquid Chromatographic Methods Used for Extractables Screening. J. Liq. Chromatogr. Relat. Technol. 2016, 39 (13), 613–619.
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PDA Journal of Pharmaceutical Science and Technology: 75 (3)
PDA Journal of Pharmaceutical Science and Technology
Vol. 75, Issue 3
May/June 2021
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The Implications of Chromatographically Screening Medical Products for Organic Leachables Down to the Analytical Evaluation Threshold Adjusted for Response Factor Variation
Dennis Jenke, Ted Heise
PDA Journal of Pharmaceutical Science and Technology May 2021, 75 (3) 273-288; DOI: 10.5731/pdajpst.2020.012013

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The Implications of Chromatographically Screening Medical Products for Organic Leachables Down to the Analytical Evaluation Threshold Adjusted for Response Factor Variation
Dennis Jenke, Ted Heise
PDA Journal of Pharmaceutical Science and Technology May 2021, 75 (3) 273-288; DOI: 10.5731/pdajpst.2020.012013
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  • Article
    • Abstract
    • Introduction: Extractables, Leachables, and the Analytical Evaluation Threshold
    • Problem Statement: The Analytical Evaluation Threshold Gap
    • Filling the Analytical Evaluation Threshold Gap with the Uncertainty Factor
    • Current Practice with Regard to Establishing the Magnitude of the Uncertainty Factor
    • Issues with the Use of Large Uncertainty Factors to Adjust the Analytical Evaluation Threshold
    • Managing the Uncertainty Adjustment
    • Conclusion
    • Conflict of Interest Declaration
    • References
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Cited By...

  • Addressing Medical Device Extractables and Leachables via Non-Target Analysis (NTA); The Analytical Evaluation Threshold (AET) and Quantitation
  • Standardization of Chromatographic Screening Methods for Organic Extractables and Leachables by Managing Outcomes
  • A Practical Derivation of the Uncertainty Factor Applied to Adjust the Extractables/Leachables Analytical Evaluation Threshold (AET) for Response Factor Variation
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Keywords

  • Extractables
  • Leachables
  • Analytical Evaluation Threshold
  • AET
  • Response factor variation
  • Uncertainty Factor

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