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   Pharmacuetical General Mission
                                       and Values
                                      Highlighting following values
                                          Be Science Based
                                          Create value for patients
                                          Ensure quality
                                      Variability of International
                                       Regulations
                                      Variability in distribution settings on
                                       International level
                                      Pipeline Clinical Trials (Antibodies
                                       / Proteins)
                                      Temperature Monitoring and
                                       related deviations
Werner Stilmant
Cold Chain Specialist                 Bench Marking
LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
   Protein/Anti-body Structure
                                          Primary
                                          Secondary
                                          Tertiary
                                          Quaternary
                                      Denaturation
                                          Triggered by Heat /
                                           Cold, pressure, PH, etc.
                                          Irreversible affected by Temperature
                                           shock
                                          Unfolding Temperature
                                          Irreversible reactions
                                          Differences with small molecules
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
   All curent and future products
                                       follow Arrhenius equations
                                      No impact analysis of different
                                       temperature spikes (shock)
                                      “Regulatory agancies agree
                                       per definition with Pharma
                                       strategy ”? Defendable on
                                       International level ?
                                      (ICH) required stability data
                                       sufficient to sustane strategy.



Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Temperature excursions
                                   • During monitored shipments
                                   • What about none monitored shipments ?




                                   Country specific regulatory requirements
                                   • Variable within International Environment
                                   • Requesting more and more monitoring during shipping
                                   • Considering more and more storage conditions as being
                                     applicable for shipping conditions

                                   Every shipment being unique
                                   • By averaging you risk of ignoring worst case settings
                                   • Difficult to defend towards agancies with growing know-
                                     how on cold chain aspects

Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Positive   Negative




Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
   Definition: “The ease with which heat flows through a material is measured
                                       by its thermal conductivity. The higher the conductivity, the easier the heat
                                       flow.”




                                      Comparing EPS with PU results it is clear that sudden changes in ambient
                                       temperatures (spikes) will be reflected more in EPS shippers.
                                      Sudden (frequent) spikes (temp shocks) can have a negative impact on
                                       protein structure (product specific) or effect on expiry period
                                      MKT will average this out, while chances of encountering spikes are higher
                                      Vacuum technologies not that often used within current configurations.
                                       Potential ?




Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Ambient



                                   0 – 25 °C



                                   15 – 25 °C




                                    2 – 8 °C
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Additional slides /
                                   Further Information




Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist
                          Note : ∆H USP refers to a generic activation energy of 83.14 kJ/mol)
LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
• Singh, S.P. , Burgess, G and Singh , J (2008). Performance Comparison of Thermal Insulated Packaging
                                   Boxes, Bags and Refrigerants for Single-parcel Shipments. Packaging Technology and Science, 21-35.




Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Kim Huynh Ba
                                   Kim.huynhba@pharmalytik.com
                                       http://pharmalytik.com/




Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant
Werner Stilmant
Cold Chain Specialist

LINKEDIN PROFILE Werner Stilmant

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Mkt always applicable

  • 1.
  • 2. Pharmacuetical General Mission and Values  Highlighting following values  Be Science Based  Create value for patients  Ensure quality  Variability of International Regulations  Variability in distribution settings on International level  Pipeline Clinical Trials (Antibodies / Proteins)  Temperature Monitoring and related deviations Werner Stilmant Cold Chain Specialist  Bench Marking LINKEDIN PROFILE Werner Stilmant
  • 3. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 4. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 5. Protein/Anti-body Structure  Primary  Secondary  Tertiary  Quaternary  Denaturation  Triggered by Heat / Cold, pressure, PH, etc.  Irreversible affected by Temperature shock  Unfolding Temperature  Irreversible reactions  Differences with small molecules Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 6. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 7. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 8. All curent and future products follow Arrhenius equations  No impact analysis of different temperature spikes (shock)  “Regulatory agancies agree per definition with Pharma strategy ”? Defendable on International level ?  (ICH) required stability data sufficient to sustane strategy. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 9. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 10. Temperature excursions • During monitored shipments • What about none monitored shipments ? Country specific regulatory requirements • Variable within International Environment • Requesting more and more monitoring during shipping • Considering more and more storage conditions as being applicable for shipping conditions Every shipment being unique • By averaging you risk of ignoring worst case settings • Difficult to defend towards agancies with growing know- how on cold chain aspects Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 11. Positive Negative Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 12. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 13. Definition: “The ease with which heat flows through a material is measured by its thermal conductivity. The higher the conductivity, the easier the heat flow.”  Comparing EPS with PU results it is clear that sudden changes in ambient temperatures (spikes) will be reflected more in EPS shippers.  Sudden (frequent) spikes (temp shocks) can have a negative impact on protein structure (product specific) or effect on expiry period  MKT will average this out, while chances of encountering spikes are higher  Vacuum technologies not that often used within current configurations. Potential ? Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 14. Ambient 0 – 25 °C 15 – 25 °C 2 – 8 °C Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 15. Additional slides / Further Information Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 16. Werner Stilmant Cold Chain Specialist Note : ∆H USP refers to a generic activation energy of 83.14 kJ/mol) LINKEDIN PROFILE Werner Stilmant
  • 17. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 18. • Singh, S.P. , Burgess, G and Singh , J (2008). Performance Comparison of Thermal Insulated Packaging Boxes, Bags and Refrigerants for Single-parcel Shipments. Packaging Technology and Science, 21-35. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 19. Kim Huynh Ba Kim.huynhba@pharmalytik.com http://pharmalytik.com/ Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 20. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 21. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant
  • 22. Werner Stilmant Cold Chain Specialist LINKEDIN PROFILE Werner Stilmant