challenges behind the scenes of clinical pet tracer production · 7/1/2017 · challenges behind...
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Ashley Mishoe, PharmD Cyclotron Facilities Manager
UCSF
Field Notes #1:
Challenges Behind the Scenes of Clinical PET Tracer Production
Goal: F-18-Mishoe
2
Introduction - Pre- Go Live Days – Production - Quality Control - Regulatory Affairs - Communication
Assumptions GMP
facility Cyclotron is working ALARA
I am not a chemist Disclaimer
Ashley Mishoe, PharmD
Pre- Go Live Days
3
Production - Pre- Go Live Days – Production - Quality Control - Regulatory Affairs - Communication
Starting Materials
Money
GMP grade
Backup supply
Final product
vials
Ashley Mishoe, PharmD
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Number of manipulations
Production - Pre- Go Live Days – Production - Quality Control - Regulatory Affairs - Communication
Media Fill
Storage of vial
Length of process
Worse Case
Scenario
Ashley Mishoe, PharmD
Go Live Day
5
When the Go Live Day
becomes
One of Those Days
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Ashley Mishoe, PharmD
Cyclotron
Radio chemistry
Quality Control
6
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
✓
Ashley Mishoe, PharmD
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Synthesis Module
o Setup checks
o Heater
o Syringe drives
o Actuators
o Vacuum
o Determine schedule
o Back-up synthesis module
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Radio chemistry
Ashley Mishoe, PharmD
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Activity trapped
GO
Walk away
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Radio chemistry
X Ashley Mishoe, PharmD
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Know the Trace! o Where is the activity going?
o Can you move it forward?
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Radio chemistry
Ashley Mishoe, PharmD
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Cameras inside module o Visualize key steps in reaction
o Precursor
o Eluent
o Monitor syringe drives
o Can you save the production batch?
o *ALARA
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Radio chemistry
Ashley Mishoe, PharmD
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Final Manufacturing Steps o Intermediate/Formulation vial
o Air locked filter
o Final product pushing to final product vial
o Acquiring all of the activity
o Build in extra push
o Final product sticking to filter
o Extra rinse
o Assay filter separately
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Radio chemistry
Ashley Mishoe, PharmD
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Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Cyclotron
Radio chemistry
Quality Control
✓
✓
Ashley Mishoe, PharmD
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Filter Integrity Test o Bubble point
o EtOH content
o Water rinse prior to testing
o Out of Specification vs part of
procedure
o Reprocessing batch
Production - Pre- Go Live Days – Production- Quality Control- Regulatory Affairs - Communication
Quality Control
Ashley Mishoe, PharmD
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Residual Solvents o Phantom peaks
o Consider products tested immediately before
o Burn out
o Extra water rinse
Production - Pre- Go Live Days – Production- Quality Control- Regulatory Affairs - Communication
Quality Control
Ashley Mishoe, PharmD
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Production - Pre- Go Live Days – Production- Quality Control- Regulatory Affairs - Communication
Cyclotron
Radio chemistry
Quality Control
✓
✓
✓ Doses to Clinic ✓
RELAX?
FORM 482
Ashley Mishoe, PharmD
Keep the Lab Legal
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Lab Registration
o FDA
o State registration
o Animals vs humans
o Practice of Medicine vs
Practice of Pharmacy
Regulatory Affairs
Production - Pre- Go Live Days – Production- Quality Control- Regulatory Affairs- Communication
Ashley Mishoe, PharmD
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Investigations o Just a form to complete
vs
o Active role in improving the process
o True root cause
o True preventive action
o Make your future life easier
Production - Pre- Go Live Days – Production- Quality Control- Regulatory Affairs- Communication
Regulatory Affairs
Ashley Mishoe, PharmD
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Production - Pre- Go Live Days – Production- Quality Control- Regulatory Affairs- Communication
Communication
Can we have some more? 1. Explain the process
2. Expiration of product
Ashley Mishoe, PharmD
UCSF Cyclotron Team Salma Jivan Allan Rosete, PharmD Irfan Javed, PhD Jeff Krug Bill Mannone Jim Slater, PhD
Acknowledgments
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