INTRODUCTION Viral shedding is crucial for Gene Therapy Products - PowerPoint PPT Presentation

INTRODUCTION Viral shedding is crucial for Gene Therapy Products Safety linked with shedding data – For the patient – For families and friends – For the environment No treatment possible without good safety results Shedding studies must be conducted properly

THE STRATEGY Viral shedding must be evaluated early in Phase I and through all phases Launch requires strong data Viral shedding evaluation is mandatory and costly What is the best approach? A clinical trial dedicated to viral shedding evaluation?

VIRAL SHEDDING EVALUATION Test selection is very complex Multiple parameters have to be considered to obtain strong data – Sample type – Sampling times – Logistical issues – Analysis and method validation

SHIPMENT SAMPLES VIRAL SHEDDING TESTS AND METHODS COLLECTION STORAGE

SHIPMENT SAMPLES VIRAL SHEDDING TESTS AND METHODS COLLECTION STORAGE TEST AND METHODS TEST AND METHODS No routine testing Methods developed according to viral construct Very sensitive tests using cellular and molecular methods Test validation is crucial Lab selection based on strong partnership

SHIPMENT SAMPLES VIRAL SHEDDING TESTS AND METHODS COLLECTION STORAGE Multiple sample types for full evaluation SAMPLING SAMPLING Multiple sampling points requested Test results depend on the quality of the samples Sample collection process is crucial

SHIPMENT SAMPLES VIRAL SHEDDING TESTS AND METHODS COLLECTION STORAGE COLLECTION COLLECTION Collection procedures Clinical site training Sampling kits Clinical site monitoring Labeling

EXAMPLES Collection procedure Sampling kits COLLECTION COLLECTION Issues – Preparation issues – Labeling issues • Mix up between patient and household member • Tubes not labeled – Timing issues • Tubes not collected at baseline but after treatment • Tubes not collected

COLLECTION PROCEDURE COLLECTION PROCEDURE Draw blood slowly, using a syringe if possible, and the largest-bore catheter that is feasible for the patient. Transfer blood to a CTAD vacutainer tube (Hemogard, sedimentation rate determination 4.5 mL tubes), being careful to minimize agitation of the sample. Gently mix tube by inverting 4 times Centrifuge at 2000 X g for 15 minutes at room temperature within 1 hour of blood draw. Within 30 minutes after centrifugation, draw off plasma very slowly with transfer pipette to within 0.5 cm of the buffy coat, taking great care not to disturb the buffy coat (any contamination may invalidate the assay). Pipette the plasma specimen into two separate plastic cryovials. Complete corresponding lines for each blood draw on the shipping log. Include patient identification number, initials, and date of specimen collection. All specimens must be stored frozen at -20°C (or colder) in a freezer The Specimen Log Sheets must be completed and included along with all shipments Only the primary samples of each patient should be sent with the first shipment to ensure that duplicates are available at the site for backup in case of damage during shipment.

SHIPMENT SAMPLES VIRAL SHEDDING TESTS AND METHODS COLLECTION STORAGE STORAGE STORAGE Qualified Freezer / Refrigerator Restricted area Monitored temperature equipment Storage documentation requirements

SHIPMENT SAMPLES VIRAL SHEDDING TESTS AND METHODS COLLECTION STORAGE Select the best shipping temperature Courier selection SHIPMENT SHIPMENT Cold chain management Shipping materials Shipping requirements Shipping issues

SHIPMENT - SELECT THE BEST SHIPPING TEMPERATURE Select the best shipping temperature Depends on the stability of the viral construct Courier selection – The best but also the easiest to manage Cold chain • -20°C versus dry ice Management – Viral construct is temperature sensitive Shipping • Impact of Thawing / Freezing issues Materials Shipping Requirements Shipping issues

SHIPMENT – COURIER SELECTION Select the best shipping temperature Courier Some parameters will impact the selection selection – The nature of the samples – The clinical site and testing lab locations Cold chain Management – The level of internal expertise – The QA requirements Shipping – The budget Materials Different courier types for different needs – Support Shipping Requirements – Training Shipping issues

SHIPMENT – COLD CHAIN MANAGEMENT Select the best shipping temperature Courier Viral products are temperature sensitive selection Most of the time, frozen shipment under Cold chain Management dry ice, or at +2°C+8°C with gel packs – Cold chain must be well managed Shipping – Packaging selection is crucial Materials – Temperature probe – Strong partnership with a courier Shipping Requirements Shipping issues

SHIPMENT – COLD CHAIN MANAGEMENT EXAMPLE: Temperature impact Shipment under dry ice Biological samples containing adenoviral construct Lack of cold chain management Freeze / Thaw accident – Decrease in viral concentration – False negative shedding results

SHIPMENT – COLD CHAIN MANAGEMENT Shipment of biological samples: -80°C

SHIPMENT – SHIPPING MATERIAL Select the Packaging validation best shipping temperature Courier selection Cold chain Management Ambient temperature Shipping Materials Dry ice probe N ° 1 Shipping Plastic Tube Probe N ° 2 Requirements Probe N ° 3 Shipping issues

Product -60°C

SHIPMENT – SHIPPING MATERIAL Select the best SOLUTIONS shipping temperature ALL PACKED IN ONE Courier selection Cold chain Management Shipping Materials Shipping Requirements Shipping issues

SHIPMENT – SHIPPING REQUIREMENTS Select the best Customs, documents, shipping classification of the viral construct temperature Courier selection Cold chain Management Shipping Materials Shipping CDC Permit, others… Requirements Shipping issues

SHIPMENT – SHIPPING ISSUES Select the best shipping temperature Courier selection Packaging Cold chain Management Packaging instructions Shipping Materials Initial sample temperature Shipping Replenishment of refrigerant Requirements Shipping issues

SHIPMENT – SHIPPING ISSUES Packaging Perforation occurred during shipment Packaging Refused by airline company Samples blocked

SHIPMENT – SHIPPING ISSUES Selected option: Replace the shipping box QUESTION: • HOW to find a certified company? • HOW to transfer the responsibility of the shipment? • HOW to verify that everything is properly done? • HOW to be sure that the cold chain will be maintain

SHIPMENT – SHIPPING ISSUES Packing instructions have been followed

SHIPMENT – SHIPPING ISSUE Packing instructions have not been followed

SHIPMENT – SHIPPING ISSUE Initial product temperature: same as shipping temperature PRE-SHIPMENT 8 2

SHIPMENT – SHIPPING ISSUE Shipment Pre-Shipment Initial product temperature: different as shipping temperature : The samples have been collected few minutes before the pick-up

SHIPMENT – SHIPPING ISSUE Appropriate replenishment First replenishment Second replenishment

SHIPMENT – SHIPPING ISSUE Without replenishment Not sufficient or too late replenishment

CONCLUSION Multiple parameters could interfere in the viral shedding evaluation Strong expertise requires in all fields Harmonization through the process How to reduce shedding evaluation costs Could we use the data through different constructs / indications Specific guidelines needed

INTRODUCTION Viral shedding is crucial for Gene Therapy Products - PowerPoint PPT Presentation

INTRODUCTION Viral shedding is crucial for Gene Therapy Products Safety linked with shedding data For the patient For families and friends For the environment No treatment possible without good safety results Shedding studies must

INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION

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INTRODUCTION Viral shedding is crucial for Gene Therapy Products - PowerPoint PPT Presentation

INTRODUCTION Viral shedding is crucial for Gene Therapy Products Safety linked with shedding data For the patient For families and friends For the environment No treatment possible without good safety results Shedding studies must

INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION

INTRODUCTION Introduction 2/42 INTRODUCTION Alternations I am giving bread to the

Introduction Introduction Introduction Introduction Outline Motivation Failures

Introduction Introduction Introduction Nationwide Cause for Concern 1

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Overview Introduction to SMIL Introduction to W3C and XML Introduction to SMIL

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Previous Lecture Introduction to SMIL 2 Introduction to W3C and XML Introduction to SMIL

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2018.06 01 SMILE5 Introduction S E 5 02 Alpha Cloud M I L 03 Company Introduction 04

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Network Visualization Introduction Presented by Shahed Introduction Introduction Basic

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JABLOTRON JA-100 introduction November 2011 Introduction Todays goals First introduction of

DWI The New World of Videos &amp; Blood Tests Cameras Can Be Vicious First they frame you! Then

Edward Chew &amp; Erica Wood On behalf of the WPs on TTID and HV Interna/onal Survey on

SAN FRANCISCO GENERAL HOSPITAL and TRAUMA CENTER ANNUAL REPORT Fiscal Year 2010 - 2011 1

Data Integrity: TGA Expectations Stephen Hart Senior Inspector, Manufacturing Quality Branch, TGA

HEALTH AND SAFETY PROGRAMS: ABA PROCEDURES AND OUTCOMES Eb Blakely, Ph.D., BCBA-D

CLINICIAN Before the scheduled enrolment visit the clinician will: Review all Screening part 1

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9/28/2010 QuantiFERON Gold In-Tube: The Basics of Getting Started Richard Oatis Supervisor,

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