A New 18F-Labeled Myocardial PET Tracer: Myocardial Uptake ...
Challenges Behind the Scenes of Clinical PET Tracer Production · 7/1/2017 · Challenges Behind...
Transcript of 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
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Goal: F-18-Mishoe
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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
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Pre- Go Live Days
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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
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Go Live Day
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When the Go Live Day
becomes
One of Those Days
Production - Pre- Go Live Days – Production- Quality Control - Regulatory Affairs - Communication
Ashley Mishoe, PharmD
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Cyclotron
Radio chemistry
Quality Control
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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
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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
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UCSF Cyclotron Team Salma Jivan Allan Rosete, PharmD Irfan Javed, PhD Jeff Krug Bill Mannone Jim Slater, PhD
Acknowledgments