Stage 0: Stage 1: Stage 2: Stage 3: Stage 4: Stage 5:

Contract Initiation (Pre-PD) Development (PD) Transfer (ENG) Manufacturing (GMP) Commercialization

Process Development for History of

Gene Therapy
Fully Characterize your
Product and Process
Viral Vector Manufacturing • First conceptualized in 1972 (47 years ago!)
Early (PD) Late (Eng / GMP)
• First FDA-approved trial in 1990
A critical partnership between client and CDMO (29 years ago)
• Titer • Contaminants
• First patient treated by French Anderson • Infectious titer • Residuals

Product
in 1990. • Purity • Potency
• Stability
Generalized Gene Therapy • Identity
Manufacturing Process: Two major events halted progress: • Appearance

• U Penn trial with young patient who died • Mass Balance • Safety
(1999)

Process
• Process • Reproducibility
• France: Some X-SCID pts cured but appropriateness • Trending
developed treatable childhood leukemia. • Material/supplies
appropriateness
(2003)
• Scale assessment

Thaw and Seed Vector Lysis Filter

Expand Cells Expansion Production Benzonase® Clarification
Vessel Infection/
Transfection
Concentration
Diafiltration
Enhance Speed & Improve
Critical Factors for Successful
1st
Quality with Templated Processes
Path to Commercialization Chromatography
Avoid:
1 cGMP Compatible
• Cell banking activities • Engineering run
2nd • Tech transfer / most • Custom Bill of Material /
2 Scalable Chromatography
process development Batch Record creation

3 Reproducible 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12
Concentration Cell Bank
Final
Formulation Tech Transfer MCB WCB Gap/Risk Analysis
4 Robust
Custom

Process Development Confirmation

Engineering Limited Extensive

Sterile
Filtration Clinical BOM/BR Eng. Run Release to clinic

Confirmation GMP1 Testing

Template

PD

Clinical Limited Release to clinic

Fill and GMP1 Testing

Finish Potential savings: 14-18 months

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Literature No. MS_PS6670EN Rev. A 8/2020

2019 - 25208
09/2019