44% more yield, 58% lower costs-a gene therapy manufacturer's process transformation

The company set out to optimize viral vector production to materially lift yields and lower cost of goods while preserving GMP quality. The program needed scalable processes, stronger analytics, and rigorous regulatory alignment so improvements would transfer cleanly from development to clinical manufacturing.

• Increase volumetric yield and recovery across upstream/downstream
• Stand up fit-for-purpose analytical methods for tighter process control
• Ensure scalability and regulatory compliance from development to GMP
• Reduce COGS and expand reliable production capacity

Existing processes under-performed industry benchmarks at multiple steps. Scale-up exacerbated losses, analytics missed critical impurities, and batch failures drove material waste—all of which constrained capacity and commercial viability.

• AAV titers around 1e13 vg/L were 65% below benchmarks
• Downstream purification recovered only 35% of input material
• Scale-up attempts cut productivity by 72%
• Analytics detected only 41% of process-related impurities
• 28% batch failure rate caused $3.2M annual material loss
• COGS of $250,000 per dose limited viability

CleverX mobilized a cross-functional team to rebuild the platform from cell culture through release testing—pairing QbD with practical GMP know-how so gains would be robust, repeatable, and inspection-ready.

Expert recruitment:

• 18 specialists: 7 upstream process scientists, 6 purification experts, 5 analytical dev leads
• Avg 8 years viral vector experience; deep GMP exposure
• Skills spanning suspension culture, chromatography, qPCR/analytics
• Direct FDA CMC and BLA submission experience

Technical framework:

• High-density suspension HEK293 process to 5e6 cells/mL
• Novel 3-step chromatography train for yield and purity
• Analytical platform of 15 release/characterization assays
• QbD backbone with 30 critical process parameters (CPPs)

Quality protocols:

• Process validation aligned to ICH Q5E
• In-process controls across 20 quality attributes
• Contamination control meeting EU Annex 1
• Complete batch records and DHF-ready documentation

The work ran in focused sprints to diagnose losses, lock in improvements, and harden the process for GMP transfer—creating immediate yield gains and faster, more reliable batch execution.

Weeks 1-2: Process characterization and gap analysis

• Mapped yield loss across unit ops; analyzed 50 historical batches
• Isolated root causes; quantified $6.3M annual upside

Weeks 3-6: Process development and optimization

• Transfection efficiency lifted to 85%; fed-batch extended to 7 days
• Chromatography recovery improved 35% → 68%

Weeks 7-8: Scale-up and technology transfer

• Scaled to 200L bioreactors with yield retention
• Transferred to GMP with 3 engineering runs
• Validated analytical methods to FDA expectations

Weeks 9-10: GMP implementation and training

• Produced 3 GMP batches meeting all specs
• Trained 25 operators; launched CI program and dashboards

A tight loop between development and manufacturing ensured lab wins translated into floor performance, with clear run books and release criteria.

Efficiency gains:

Cycle times shortened and facility throughput improved without quality compromise.

• Manufacturing time reduced 6 → 4 weeks per batch
• QC testing time down 35% with streamlined methods
• Process-development cycles accelerated 48%
• Facility utilization lifted 55% → 78%

Quality Improvements:

Higher yield came with cleaner product and far fewer failures.

• Volumetric yield up 44% to 1.8e14 vg/L
• Product purity increased 92% → 98.5%
• Batch failure rate reduced 28% → 8%
• Potency assay precision improved 52%

Business impact:

Lower COGS and dependable supply unlocked access and viability.

• COGS reduced 58% to $105,000 per dose
• $3.7M annual savings from yield improvements
• 2.5× more patients supported at current capacity
• Time to commercial viability accelerated by 18 months

Strategic advantages:

A durable, scalable platform with defensible IP and partnership-ready data.

• Platform process applicable across AAV serotypes
• Manufacturing capability ready for pivotal trials
• 3 process patents filed
• CMC package enabling partnership discussions

Recognized by a leading gene therapy manufacturing consortium for excellence in vector process optimization.