Managing Nonmutagenic Impurities in Pharmaceuticals: Emerging Science (S13)

Symposium Chair(s)

• Catrin Hasselgren, PhD

  Executive Director
  Genentech
  South San Francisco, California, United States

• Michelle Kenyon, MA

  Associate Research Fellow
  Drug Safety Research and Development
  Pfizer Research and Development
  Groton, Connecticut, United States

Symposium Speaker(s)

• Joel Bercu, PhD, MPH, DABT

  Exec Director
  Gilead Sciences, Inc.
  Foster City, California, United States

• Mayur Mitra, PhD, DABT

  Distinguished Scientist
  Genentech, Inc.
  South San Francisco, California, United States

• Timothy McGovern, PhD

  Associate Director, Toxicology
  Office of New Drugs, CDER
  US FDA
  Silver Spring, Maryland, United States

• Arianna Bassan, PhD

  Principal Consultant
  Innovatune
  Padova, Veneto, Italy

• Paul Cornwell, PhD, DABT

  Executive Director
  Nonclinical Safety Assessment
  Eli Lilly and Co, Inc.

The presence of impurities and degradation products in drugs is unavoidable and it is critical that control strategies are in place to ensure patient safety. A key piece to an appropriate control strategy understanding the possible toxic effects of impurities present at low levels in drugs. ICH Q3A/B address the quality and safety aspects of impurities in pharmaceuticals at product registration and include guidance on a qualification threshold dependent on the amount of drug administered, above which safety studies may be needed to establish the biological safety of an impurity. Although general study design considerations are discussed in the guidance, an IQ DruSafe Impurities Working Group survey identified some aspects of the qualification process that could benefit from harmonization, such as aspects of study design, as well as a defined approach for calculating a safe limit based on qualification data. Additionally, although it is recognized that higher qualification thresholds may be appropriate during clinical development or for short duration commercial products, data-driven safety-based limits are lacking. Finally, current qualification approaches do not consider 3R approaches for hazard assessment. This symposium will discuss recent recommendations for a harmonized approach that includes a 3R-based study design. A recent data analysis effort to identify classes of compounds that may require a lower qualification threshold will be discussed, as well as an analysis of nonclinical toxicology studies to aid in setting safety-based qualification thresholds during clinical development. Finally, there will be a discussion of possible future directions for impurity qualification, including new approach methodologies.

Presentations:

• 2:00 PM - 2:05 PM CT

  Welcome
  

  Symposium Chair: Catrin Hasselgren, PhD – Genentech

  Symposium Chair: Michelle Kenyon, MA – Pfizer Research and Development
• 2:05 PM - 2:30 PM CT

  Overview of Impurity Qualification and How is it Used by Chemistry?
  

  Symposium Speaker: Joel Bercu, PhD, MPH, DABT – Gilead Sciences, Inc.
• 2:30 PM - 2:55 PM CT

  Best Practices in Impurity Qualification Study Design, 3R Considerations
  

  Symposium Speaker: Mayur Mitra, PhD, DABT – Genentech, Inc.
• 2:55 PM - 3:15 PM CT

  Durationally Adjusted Qualification Threshold
  

  Symposium Speaker: Michelle Kenyon, MA – Pfizer Research and Development
• 3:15 PM - 3:45 PM CT

  Break
• 3:45 PM - 4:00 PM CT

  US Regulatory Perspectives on the Safety Assessment of Non-mutagenic Impurities in Pharmaceuticals
  

  Symposium Speaker: Timothy J. McGovern, PhD – US FDA
• 4:00 PM - 4:15 PM CT

  Analysis of Non-Mutagenic Substances in the Context of Drug Impurity Assessment—Few are Potent Toxicants
  

  Symposium Speaker: Paul Cornwell, PhD, DABT – Eli Lilly and Co, Inc.

  Symposium Speaker: Catrin Hasselgren, PhD – Genentech
• 4:15 PM - 4:35 PM CT

  In Silico Methods for the Derivation of Quantitative Safety Limits
  

  Symposium Speaker: Arianna Bassan, PhD – Innovatune
• 4:35 PM - 5:00 PM CT

  Panel Discussion