MedScope - Tech Transfer Summary
MedScope has substantial experience in the field of biologics QbDTech Transfer, particularly in the Gene Therapy Clinical Manufacture Space. Whether Tech Transfer is site to site, development to cGMP, scale up, scale down, or scale up, FDA regulatory inspections, or PAI, the Medscope team rigorusly follows the QbD principles of ICHQ6, ICHQ8, ICHQ9, and ICHQ10, thereby enabling more expedient development timelines with regulatory authorities. MedScope is a rapid development organization, and in most instances can initiate value-based discussions within 24 hours. Please contact us at 802-236-8650 or info@medscope.com.
MedScope - Key TechTransfer Principles
- QbD All Unit Ops, Beginning To End
- Scale-up/Scale-down/Scale-out As Tech Transfer
- Continuous Manufacture w/PAT When Possible
- Use Closed Systems, Single Use
MedScope - Tech Transfer w Gene Therapy(GT)
2019 Clinical Trials
- 372 Gene Therapy Trials In Progress (123 Ph I, 217 Ph II, 32 Ph III)
Technology/Manufacturing Acquisitions In GT
- Catalent Acquiring Paragon (GT) ($1.2 Billion)
- Thermo Fisher Acquiring Brammer Bio (viral vector) ($1.7 Billion)
- Agilent Acquiring BioTek (cell imaging) ($1.2 Billion)
Approvals In GT
- Luxturna (1st in vivo GT Approved 12/2017, Priority Review/Breakthrough Therapy/Orphan Drug, GT Inherited Form Vision Loss, AAV)
- Zynteglo (Bluebird Bio, EMA Approval 6/2019, GT blood disease, Lenti Vector)
- Zolgensma (Novartis(AveXis), FDA Pediatric Approval 5/2019, GT Spinal Muscular Atrophy, AAV9)
Delays In GT
- Zynteglo 2020 Delay Due To EMA Request Tighten Drug Product Spec, Manufacturing Process
MedScope - Tech Transfer Project Management in GT
- Integrate Technical (QbD, Risk Management), Quality, & Regulatory Management
- Phased Development w/ Gating Decision Point (DP) Each) Tech Transfer
- Types of Manufacturing Processes, Regulatory Definitions
- Batch vs Continuous Unit Operations, Advantages and Disadvantages
- Integrate and risk manage QTPP/CQA with CPP/CMA, Implement In Process Measures
- Equipment Design Early On, Closed, Sterile, SU When Possible, Engineering DOE Runs to Ensure Product /Process Robustness
MedScope - Tech Transfer Integrating Technical/Quality/Regulatory Planning and Risk Management
- Implement Quality Technical Agreements Where Possible
- Work To Understand/Obtain Cross Functional Regulatory Agreement
- Utilize QbD w Manufacturing DOE's To Define Design Space, Create Control Strategy
- Utilize Risk Management Principles w High/Medium/Low Risk Ranking To Structure Submission
MedScope - Tech Transfer Lab to Pilot Clinic Scale
Primary Development Goals: Initiate QTPP and QbD, Regulatory Path, Clinical Outcome, Preserve Product Continuity
Common Tech Transfer Issues: Evolving QTPP, Raw Materials, RFT Failure, Undefined CQA, Unknown Link CQA to CPP/CMA, Inappropriate Equipment, Insufficient Spend & Process Knowledge, Stability, Contamination
MedScope - Tech Transfer Pilot to Pivotal Scale
Primary Development Goals: Finalize QTPP, Implement QBD, Link CPP and CMA to CQA, Scale w/in 10x Commercial, Develop Control Strategy, Clinical Outcome, Preserve Product Continuity
Common Tech Transfer Issues: Evolving QTPP, Raw Materials, RFT Failure, Inappropriate Equipment, Insufficient Spend, Process Knowledge, Insufficient Stability, Short Time
MedScope - Tech Transfer Pivotal to PPQ Scale
Primary Development Goals: Scale to Commercial, Adjust CPP and CMA to CQA Scope w/in Global Regulatory Strategy. Robust Equipment and Process,PPQ and CPV, Product Continuity
Common Tech Transfer Issues: Significant CAP Spend & Risk, Shared Equipment (cleaning), Significant COGS, Regulatory Constraints Upon Upscale, IP Constraints, Training New Personnel
MedScope - Tech Transfer Manufacture Outsource
Primary Development Goals: Implement External Process, Reduce CAP and COGS,Leverage Knowledge, Scale Up, Product Continuity
Common Tech Transfer Issues: IP, Exclusivity, Tech Agreement, Training, Knowledge Preservation, Equipment Differences, Financial,Comparability SU to RU
MedScope - Tech Transfer Manufacture Process Change
Primary Development Goals: Improve Yields, Improve Quality and Process Robustness, Change CPP and/or CMA While PreservingCQA, Reduce COGS, IP, Preserve Product Continuity
Common Tech Transfer Issues: Global Regulatory Constraints, CAP,Costs, Time to Acquire New Knowledge, Risk of Non-‐approval, Regulatory Burdens (eg.Comparability Study toImplement)
Tech Transfer Process Change Examples: (possible trigger Comp Study CFR 601.12(e)…), ICH Q5E
Ex. Change manufacture during scale up. Need Well-defined CQA and Validated Test Methods
MedScope - QbD: Quality Assurance Achieved by Robustness of the Product/Process Design (ICH Q8(R2), ICH 11 (/Q5-7/Q11)), ICH Q6B, Tech Transfer
- Quality Target Product Profile (QTPP) & Critical Quality Attributes (CQA) for QTPP
- DS vs. DP
- Determine Critical Material Attributes (CMA)/Critical Process Parameters (CPP) Affect CQA
- Standard Product Characterization
- Viral Contaminants
- Endotoxin
- Sterility
- Dose(cell number, mass, titer (different stages), LV vector titre, copy number
- Reference: OCTGT web seminars on “The chemistry,manufacturing and controls (CMC) section of a gene therapy IND” and “Cellular Therapy Products”
MedScope - Quality Risk Management (QRM)
- Identify / Assess-Rank / Control / Review (ICH Q9),Tech Transfer
- Identify / Assess-Rank / Control / Review (ICH Q9),Tech Transfer- Identify in-process Quality Attributes necessary for each unit operation (and/or product CQA), Define AC
Eg. Viscosity, Temperature, pH, DO, Conductivity, etc.
- Identify CPP affecting in process quality attributes, Implement Control Loops
Eg. Equipment Controls – pH, Metered Flow Rates; PAT Controls (via integrated NIR, Raman, etc.)
- Identify potential impact of equipment design and operating principle on Quality Attributes and CPP
- Relative Risk Ranking – Definitions (qualitative ranking, enable risk rank technical discussions/data) vs. FMEA (RPN#)
MedScope - Pharmaceutical Quality System (PQS) - Phases (stages) of Product Lifecycle(ICH Q10),Tech Transfer
(ICH Q10),Tech Transfer- Integrated Tech Transfer within and between Sites, Use Change & Control Strategy to Ensure Continuity
