Comprehensive AAV Gene Therapy CMC Services
SMAT Consultants provides comprehensive, phase-appropriate CMC support for drug developers, manufacturers, CDMOs, and investors working on AAV-based gene therapies. Engagements range from project-based and retainer consulting to fractional or interim CMC leadership requiring senior CMC oversight without a full-time hire.
For drug developers, our services span vector design optimization, manufacturing and process development (AAV plus plasmid), analytical characterization, regulatory and quality strategy, technology transfer, CDMO selection and oversight, as well as IND-enabling and BLA CMC support. For manufacturers and CDMOs, we focus on process and analytical optimization, operational cleanroom design, technology transfer, and GMP readiness. For investors and strategic partners, we provide technical due diligence, manufacturing feasibility assessment, COGS analysis, and portfolio company CMC support.
We combine deep scientific expertise with practical business acumen to support clients through complex CMC challenges — managing risk, timelines, budgets, and regulatory requirements across the AAV development lifecycle.
Vector Design & Optimization
Vector design decisions drive both therapeutic outcomes and manufacturing economics — performance and manufacturability are largely independent considerations that need to be balanced deliberately. We support drug developers, manufacturers, as well as CDMOs across vector design and manufacturability assessment for AAV programs.
Vector Design Services:
Capsid selection and serotype optimization for target tissue
ITR design consideration selection (single-strand vs. self-complementary)
Terminal resolution site (TRS) modification design for scAAV
D-sequence identification and characterization
Promoter selection (including tissue-specific promoters) and expression cassette optimization
Regulatory element selection and positioning strategy (polyA signals, introns, WPRE, microRNA target sites, etc.)
Codon optimization strategies
CpG content optimization
Payload capacity assessment and optimization
Transgene stability evaluation
Regulatory strategy for novel vector design modifications and comparability assessments
Manufacturability Assessment:
Plasmid design for optimal AAV yields
Plasmid system architecture selection (dual vs. triple plasmid systems for transient transfection)
Helper system evaluation (traditional and minimal helper approaches)
Production efficiency assessment of capsid variants
Empty capsid propensity assessment of different constructs
Manufacturability assessment of difficult-to-package payloads
Scale-up planning and risk assessment
Integrated Vector Design & Optimization:
Vector design decisions affect therapeutic performance and manufacturing scalability simultaneously. We help anticipate how capsid, genome configuration, payload, and regulatory element choices affect yield, scale-up, and program economics down the line.
Plasmid Design & Manufacturing
Plasmid DNA design and quality directly affect AAV yield, vector integrity, and regulatory acceptability. We support drug developers, manufacturers, as well as CDMOs across plasmid design, banking, GMP manufacturing strategy, and quality analytics for AAV programs.
Plasmid Design:
Plasmid backbone optimization (size reduction, removal of unnecessary sequences)
Antibiotic resistance marker selection and antibiotic-free selection system evaluation
Origin of replication selection and copy number optimization
Plasmid architecture optimization for ITR stability during bacterial production
Plasmid design strategies for multimer and dimer prevention
Replication-competent AAV (rcAAV) risk mitigation through plasmid redesign
Plasmid stability assessment and improvement
Vendor coordination for plasmid production implementation
Regulatory strategy for plasmid system and design choices
Plasmid Banking:
Bacterial cell bank generation strategy and coordination
Working bank qualification strategy and protocol design
Stability and quality testing program design
Regulatory documentation strategy and preparation
GMP Manufacturing:
Bacterial strain selection (Stbl2, SURE, DH10B, and other strains for ITR stability and yield optimization)
Fermentation process optimization and technology evaluation
Purification method review and improvement recommendations
Endotoxin and RNA removal strategy optimization
Regulatory-grade documentation guidance
Plasmid Quality & Analytics:
Identity testing strategy (restriction mapping, sequencing, NGS-based identity verification)
Purity assessment protocols (endotoxin, RNA, chromosomal DNA, residual host cell protein)
Structural integrity analysis (supercoiling form analysis via CGE, AGE)
Stability testing program design
Release testing specification development
Integrated Plasmid Strategy:
Plasmid manufacturing decisions made in isolation often surface as AAV manufacturing problems months later. We help anticipate how plasmid design and quality choices affect downstream AAV yield, vector integrity, and regulatory submissions — bringing integrated plasmid expertise grounded in AAV manufacturing experience.
Cell Line Strategy & Development
Cell line decisions drive AAV yield, batch consistency, and scale-up risk. We support drug developers, manufacturers, as well as CDMOs across cell line development, banking, advanced cell line strategies, and platform selection — for in-house programs and external manufacturing.
Cell Line Development & Optimization:
Cell line adaptation to suspension growth and serum-free conditions
Clonal selection and screening protocols
High-throughput clonal screening for productivity selection
Cell line characterization and genetic stability
Cell line productivity benchmarking across serotypes
Cell Banking & Documentation:
Master cell bank (MCB) generation and qualification
Working cell bank (WCB) development
Cell bank stability monitoring program design
Regulatory documentation strategy and preparation for cell banks
Advanced Cell Line Strategies:
Stable producer cell line generation (AAV + transgene)
Packaging cell line development (capsid + Rep)
Multi-plasmid stable integration strategies
Cell line licensing and freedom-to-operate assessment
Platform Capabilities:
Platform selection guidance based on program requirements
HEK293-based systems
SF9/baculovirus platforms
Alternative mammalian cell lines
Suspension vs. adherent systems
Platform-specific regulatory strategy
Integrated Cell Line Strategy:
Cell line decisions cascade across program phases — early development choices shape banking strategy, banking decisions affect regulatory submissions, and platform choices constrain advanced cell line options. We design integrated cell line strategies — across development, banking, advanced approaches, and platform selection — that match phase-appropriate program needs.
Drug Substance Process Development & Manufacturing
Upstream Process Development & Manufacturing
Upstream process decisions drive AAV titer, vector quality, and batch-to-batch consistency. We support drug developers, manufacturers, as well as CDMOs across the upstream workflow — from transfection through cell culture and productivity optimization to manufacturing scale-up.
Production Platform Selection:
Transient transfection systems (HEK293)
Baculovirus/SF9 systems
Stable producer cell lines
HSV helper systems
Platform comparison for your specific vector
Transfection Optimization:
Method comparison (PEI, calcium phosphate, lipid-based)
Transfection reagent screening and optimization
DNA-reagent complex formation protocol design
Plasmid ratio optimization
Timing and feeding strategy development
Scale-up planning from bench to manufacturing
Cell Culture Optimization:
Cell density assessment at transfection
Media selection and optimization
Feed strategy selection (batch, fed-batch, perfusion)
Harvest timing recommendations based on productivity and quality
Viral vector aggregation prevention through process design
Productivity Enhancement:
Yield optimization strategies
Process parameter screening (DoE approaches)
Critical process parameter (CPP) identification
Process monitoring and control framework
Media and raw material sourcing planning
Scale-Up Support:
Bench-to-commercial scale-up planning (small scale through pilot to commercial)
Bioreactor selection and specification (Ambr15/Ambr250 development scale through stirred tank manufacturing scale)
Process performance characterization across scales
CPP and CQA verification at scale
Tech transfer support coordination with manufacturing site
Downstream Process Development & Manufacturing
Purification strategy decisions shape AAV product quality, yield economics, and regulatory submission strength. We work with drug developers, manufacturers, as well as CDMOs across the purification train — from clarification through capsid separation to final polishing.
Clarification:
Depth filtration optimization
Flocculation pretreatment design
Filter sizing and selection
Fouling mitigation strategies
Benzonase treatment recommendations
Centrifugation alternative assessment
Primary Purification:
Affinity chromatography selection and optimization (POROS CaptureSelect, AVB Sepharose, AVIPURE)
Heparin chromatography assessment and optimization
Monolith chromatography evaluation
Platform method development for multiple serotypes
Empty/Partial/Full Capsid Separation:
Ion exchange chromatography selection (Capto Q, Capto Q ImpRes, other AEX resins)
Ion exchange gradient optimization
Ultracentrifugation assessment (CsCl, iodixanol alternatives)
Combination strategies for challenging serotypes or high purity requirements
Analytical method development for monitoring (AUC, AEX-HPLC)
Polishing & Concentration:
TFF/ultrafiltration design
Size exclusion chromatography qualification
Buffer exchange evaluation
Concentration factor optimization
Aggregate removal strategy and method development
Viral Clearance:
Evaluation of clearance by individual purification steps
Nanofiltration evaluation
Clearance study design
Integrated Drug Substance Process Development & Manufacturing:
Upstream and downstream decisions are linked — upstream process choices affect downstream impurity profiles, productivity drives downstream throughput, and harvest conditions shape purification challenges. We help anticipate and manage these interactions across the full drug substance workflow, optimizing both halves of the process together rather than sequentially.
Drug Product Process Development & Manufacturing
Drug product decisions drive AAV stability, sterility assurance, and regulatory submission strength. We support drug developers, manufacturers, as well as CDMOs across the drug product workflow — from formulation development and container/closure compatibility through fill-finish operations to cold chain distribution.
Formulation Development:
Excipient screening and selection
Buffer system selection and optimization
pH and ionic strength optimization
Surfactant evaluation (Poloxamer P188, polysorbate 20/80)
Cryoprotectant screening
Stability enhancement strategies
Freeze-thaw study design
Long-term and accelerated stability program design
Osmolality and tonicity adjustments for administration route
Container/Closure & Device Compatibility:
Vial material evaluation (glass types, plastic)
Stopper and seal compatibility evaluation
Extractables and leachables study design
Storage container optimization
Syringe compatibility assessment
Administration device compatibility assessment
Fill-Finish Process Development:
Sterile filtration strategy design
Disinfection strategy development (routine and post-spill protocols for aseptic operations)
Aseptic filling process development
Fill volume and overfill optimization
In-process and release testing strategy
Visual inspection criteria development
Container closure integrity testing approach
Cold Chain & Distribution:
Packaging strategy assessment
Shipping validation study planning
Temperature excursion study design
Global distribution planning
Stability-indicating method development
Integrated Drug Product Process Development & Manufacturing:
Drug product decisions cascade across formulation, container/closure, fill-finish, and cold chain — formulation must accommodate vector aggregation tendencies, drug substance titer determines fill volume which can constrain administration feasibility, and aggregation behavior affects sterile filtration recovery and final yield. We help design these decisions together to optimize stability, sterility assurance, and commercial supply continuity.
Analytical Development & Characterization
Vector Characterization Methods
We develop, qualify, and evaluate vector characterization methods — titer, empty/full ratio, capsid protein, and vector purity — for drug developers, manufacturers, as well as CDMOs.
Vector Quantification Methods:
Genome titer assay development by ddPCR
Capsid ELISA establishment for total capsid concentration
Optical density (A260/A280) method qualification
Method comparison and correlation studies
Empty/Full Capsid Ratio:
Method comparison and selection (AUC, AEX-HPLC, CDMS, TEM)
Method development and qualification according to program stage
Cross-method correlation studies
Capsid Protein Analysis:
VP1:VP2:VP3 ratio characteri-zation by cWB or LC-MS
Capsid protein identity confirmation by cWB or LC-MS/MS
Post-translational modification characterization by LC-MS
Vector Purity Analysis:
Aggregate analysis and characterization (SEC-HPLC, DLS, AUC)
Sub-visible particle analysis (HIAC light obscuration, MFI; USP <788>, EP 2.9.19)
Visible particle inspection method qualification (USP <790>, EP 2.9.20)
CE-SDS analysis for capsid protein purity and integrity
Potency & Infectivity Assays
We establish, qualify, and evaluate potency and infectivity assays for drug developers, manufacturers, as well as CDMOs — including phase-appropriate strategy and regulatory alignment.
Potency Assay Development:
Cell-based potency assay development by in vitro transduction
Quantitative potency assay establishment by qPCR-based transgene expression
Functional protein assay design for relevant therapeutic targets
Reporter gene system selection and method qualification
Dose-response curve generation and analysis
Infectivity Assessment:
Infectious titer determination by TCID50
Physical-to-infectious titer correlation studies (full-to-infectious ratio)
Empty capsid impact assessment on infectivity measurements
Method Validation:
Method validation strategy and protocols per ICH Q2 (specificity, linearity, accuracy, precision, range, robustness)
Stability-indicating method development and qualification
Method transfer to CROs and other testing partners
Regulatory Strategy:
Regulatory alignment strategy for potency and infectivity methods (FDA, EMA expectations)
Phase-appropriate potency assay strategy (early development through commercial)
Impurity & Safety Testing Strategy
We design, qualify, and evaluate impurity, safety, and advanced characterization testing strategies for drug developers, manufacturers, as well as CDMOs across program development.
Process-Related Impurities:
Plasmid and host cell DNA quantification by qPCR
Residual transfection reagent detection (PEI, calcium phosphate)
Residual serum component analysis (when applicable)
Residual enzyme assessment (Benzonase and other enzymes)
Safety Testing:
Sterility testing design (USP <71>, EP 2.6.1)
Endotoxin method selection (LAL or recombinant Factor C; USP <85>, EP 2.6.14)
Mycoplasma testing strategy (USP <63>, EP 2.6.7)
Adventitious agents testing approaches
Replication-competent AAV (rcAAV) detection
Residual helper virus assessment (when applicable)
Advanced Characterization:
Genome integrity analysis by NGS
ssAAV vs. scAAV genome conformation determination
Packaged DNA characterization
ITR integrity assessment
Genome truncation and deletion analysis by multiplex ddPCR
Critical quality attribute (CQA) identification and testing strategy
Integrated Analytical Strategy:
Analytical methods must evolve with the program — characterization sufficient for early development needs to mature for IND/CTA, undergo full validation for BLA/MAA, and align with regulatory expectations across submissions. We help design analytical programs that are phase-appropriate and can scale from early characterization through commercial release.
Facility & Equipment Design
Facility design decisions drive operational efficiency, GMP compliance, and scale-up readiness for the program lifetime. We support drug developers, manufacturers, as well as CDMOs across GMP manufacturing and laboratory facility design, equipment selection, utility requirements, and AAV-specific considerations.
Facility Design
Manufacturing suite layout optimized for AAV workflowsGMP laboratory layout planning for QC, release, stability, and in-process testingCleanroom classification strategy (production and fill/finish operations)Equipment placement optimization for process efficiency and GMP compliancePersonnel and material flow design (dirty/clean transitions, gowning areas)Sample flow and logistics planning within GMP laboratoriesDifferential pressure cascade designContamination control strategy and cross-contamination prevention designBiosafety cabinet and isolator placement evaluationAccess control and airlocks designMethod transfer and tech transfer readiness assessment in facility design
Equipment Selection & Strategy
Bioreactor specification and selection
Filtration equipment evaluation
Chromatography systems specification (process-scale)
TFF/UF systems selection
Automated liquid handling configuration
Analytical instrumentation qualification
Fill-finish equipment selection (semi-automated BSC/isolator vs. fully automated)
Vendor evaluation and comparison
Capital equipment prioritization
Cost-effective alternatives and value engineering
Lease vs. purchase analysis
Shared resource strategies
Equipment utilization planning
Utility Requirements
Water for injection (WFI) systems
Cooling water systems and capacity planning
Clean steam
Clean process gases (point-of-use filtration and quality)
Gas supply systems (nitrogen, CO2, O2, compressed air)
HVAC and environmental controls
Power requirements assessment and electrical distribution
Monitoring and alarm systems
Emergency backup and redundancy systems
Waste management systems
Data infrastructure (LIMS, network connectivity)
Operations & Logistics
Staffing requirements and personnel planning
Cold storage and sample management strategy
Chemical storage and handling planning
Emergency procedures development
AAV-Specific Considerations
AAV manufacturing introduces specialized facility design requirements beyond standard biologics — addressing contamination control for viral vectors, material compatibility with vector-specific disinfection agents, and equipment sizing across the clinical-to-commercial AAV scale range.
Material compatibility assessment for oxidizing disinfection agents
Contamination control strategy for viral vector production
Scale-appropriate equipment sizing strategy
Integrated Facility & Equipment Design:
Effective GMP facility design integrates manufacturing process, equipment strategy, utilities, and AAV-specific considerations from the start. We bring this perspective to GMP capability building or expansion, and apply the same expertise to process development and analytical lab design — scaling appropriately to R&D requirements without overdesigning.
Vendor Management & Tech Transfer
CDMO Selection & Management
CDMO selection and oversight decisions shape program timelines, manufacturing quality, and commercial readiness. We support drug developers in finding and managing the right manufacturing partner — and help manufacturers, as well as CDMOs, position effectively for selection and operate competitively.
CDMO Selection:
Capability assessment across multiple CDMOs
Track record and references verification
Technology platform alignment review
Site visit planning and observation
Technical audits (process, manufacturing, equipment)
Quality audit oversight and review
Quality system evaluation
Capacity and timeline evaluation
Cost comparison and negotiation support
Selection Criteria:
AAV manufacturing experience and track record evaluation
Serotype-specific expertise vetting
Scale capability screening (clinical to commercial)
Analytical capabilities assessment
Regulatory compliance history review
Financial stability and reputation review
Geographic location analysis
Contract Negotiation Support:
Technical scope definition
Technology transfer responsibilities definition
Quality agreement terms review and gap assessment
Intellectual property provisions review and coordination with IP counsel
Cost structure and payment terms analysis
Timeline commitment evaluation and risk assessment
Ongoing CDMO Oversight Support:
Project oversight and communication
Performance metrics tracking
Quality review and trending
Change control coordination
Technical problem solving
Stakeholder reporting and communication management
Technology Transfer
Technology transfer success depends on systematic planning, execution, and verification. We support drug developers, manufacturers, as well as CDMOs through process and analytical method transfers — from strategy through comparability verification.
Tech Transfer Strategy:
Critical parameter identification
Acceptance criteria definition
Risk assessment
Equipment difference management and adaptation
Raw material and reagent qualification strategy
Transfer protocol review and strategy
Timeline and resource planning
Transfer Implementation Guidance:
Knowledge transfer session facilitation
Training facilitation and qualification support
Manufacturing demonstration run support and observation
Troubleshooting guidance and optimization strategies
Process performance gap resolution between sites
Documentation review
Analytical Method Transfer:
Method transfer protocol review and strategy
Side-by-side testing design and oversight
Analytical method variability investigation and resolution
Method qualification oversight at receiving site
Specification alignment review
Ongoing method support
Comparability Studies:
Risk-based comparability strategy
Comparability protocol design
Testing strategy development
Data analysis and interpretation
Regulatory documentation strategy and review
CRO/Testing Laboratory Coordination
External testing reliability depends on careful CRO selection, method transfer, and ongoing coordination. We support drug developers, manufacturers, as well as CDMOs through testing strategy, CRO selection, method transfer, sample management, and multi-site coordination.
Testing Strategy:
Centralized vs. distributed testing strategy
Phase-appropriate testing strategy
CRO capabilities assessment
Method transfer planning
Cost optimization
Sample logistics and cold chain strategy
CRO Selection:
Analytical capability evaluation
GMP compliance assessment
Quality system review
Turnaround time and capacity evaluation
Cost comparison
Method Transfer to CROs:
Transfer protocol review and strategy
Method qualification oversight
Specification alignment review
Reference standard distribution and management
Ongoing performance monitoring
Sample Management:
Shipping and cold chain validation
Sample stability strategy
Chain of custody management
Result reconciliation
Multi-Site Coordination:
Quality agreement management
Centralized data review
Inter-site specifications alignment and harmonization
Cross-site comparison analysis
OOS investigation coordination
Integrated Vendor Management & Tech Transfer:
Vendor selection, tech transfer, and CRO coordination decisions accumulate risk across the program lifecycle — affecting program timelines, manufacturing reliability, and clinical supply continuity. We help make these decisions through independent assessment grounded in technical fit and program needs, not referral relationships or commissions.
Regulatory & Quality Strategy
CMC Regulatory Support
CMC regulatory decisions shape submission timelines, agency feedback, and approval probability. We support drug developers, manufacturers, as well as CDMOs across IND/CTA and BLA/MAA submissions — from documentation strategy through agency interactions.
IND/CTA Submission Support:
Drug substance manufacturing section
Drug product manufacturing and controls
Materials and reagents control documentation
Analytical methods and validation summary
Stability data presentation and program planning
Container closure system documentation
Manufacturing facility information
Phase-appropriate CMC documentation strategy for clinical trial materials
Quality control testing program and specifications
BLA/MAA Strategy & Oversight:
Expanded manufacturing description strategy and review
Process validation strategy and documentation review
Commercial manufacturing readiness strategy
Analytical validation summary strategy and review
Stability commitment fulfillment strategy
Comparability protocol design and study execution support
Regulatory Strategy:
Phase-appropriate development planning
Risk-based testing and control strategy
Comparability strategy across process changes
Specification setting and justification
Stability testing program design
Prior knowledge and platform technology documentation strategy
Reference standard strategy and qualification
Comparability and bridging study design for analytical method evolution (ICH Q5E)
FDA/EMA Interactions:
Pre-IND meeting preparation support
Type B and C meeting support
Response to regulatory queries and information requests
CMC deficiency response
Manufacturing change notification authoring
Quality Systems & Compliance
Quality systems decisions affect product consistency, GMP compliance maturity, and regulatory inspection readiness. We support drug developers, manufacturers, as well as CDMOs across CMC technical review, quality strategy, audits, and compliance assessments.
CMC Technical Support
CMC technical review support for batch records, investigations, and deviation assessments
CMC subject matter expert support for regulatory meetings and submissions
CMC technical assessment of manufacturing changes and comparability evaluations
GMP Strategy & Framework Review:
Manufacturing quality systems strategy and review
Batch record template review and gap assessment
Deviation management procedure review and strategy
CAPA (Corrective and Preventive Action) system strategy and review
Change control process strategy and review
Quality Control:
Release testing strategy
In-process testing program design
Stability testing protocol development
Out-of-specification (OOS) investigation support
Trending and continuous monitoring strategy
Quality Assurance:
Quality agreement review and gap assessment (with CDMOs, CROs)
Vendor qualification program strategy and review
Audit program design and CMC technical support for vendor qualification audits
Document control system strategy and review
GMP Compliance & Audit Support:
CDMO GMP audit with facility, drawing, and risk review
Phase-appropriate GMP compliance audit (clinical-stage programs)
Quality system maturity assessment
Topic-specific GMP gap analysis (deviation management, comparability, manufacturing quality)
Regulatory filing quality review
FDA facility readiness evaluation
Contamination & Environmental Control:
Cleaning validation strategy and review
Cross-contamination risk assessment
Environmental monitoring program strategy
Integrated Regulatory & Quality Strategy:
Effective CMC regulatory work depends on robust quality systems, and effective quality systems require regulatory awareness. We help design integrated strategies — across CMC documentation, quality oversight, and GMP compliance — that match phase-appropriate expectations and support successful submissions.
CMC Strategic Planning & Cost Optimization
Strategic CMC decisions shape program economics, regulatory pathway, and time-to-market. We support drug developers across CMC strategy, fractional leadership, cost optimization, and fundraising support — for clinical-stage programs through commercial readiness.
Fractional CMC Leadership & Interim CTO:
Fractional CMC leadership for pre-clinical and clinical-stage programs
Interim CTO support during organizational transitions
Company-wide CMC strategy and budget oversight
Cross-functional CMC team leadership (PD, manufacturing, QC, QA, regulatory)
Board-level CMC reporting and presentation development
Crisis management and turnaround support
Hiring and team-building support for CMC organizations
CMC Strategy & Program Planning:
CMC roadmap development from clinical to commercial
Phase-appropriate CMC strategy planning
Critical-path analysis for CMC milestones
Manufacturing strategy (in-house vs. outsource decision support)
Regulatory pathway integration and CMC strategy alignment
Risk-based CMC prioritization across program portfolio
Go/no-go decision support for CMC milestones
Stakeholder reporting framework development (board, investors, partners)
Cost Optimization & Process Economics:
Process economics modeling (cost per batch, cost per dose)
COGS modeling and projections across program phases
CDMO cost benchmarking across multiple vendors
Unit operation cost analysis (upstream, downstream, fill-finish)
Sensitivity analysis (yield, purity, titer impacts on cost)
Manufacturing yield optimization for cost reduction
Capital vs. operating expense trade-off analysis
Technology selection for cost-effective production
Scale-up cost planning and capital requirements
Fundraising & Investment Support:
Manufacturing projections and CMC narrative development for Series fundraising
CMC content development and risk assessment for investor presentations
Cost projection support for commercial planning and pricing
Pre-partnering capability disclosure and CMC due diligence preparation
CMC section review for pitch decks and confidential information memoranda (CIMs)
Manufacturing risk assessment for investor and partner audiences
CMC narrative alignment with clinical and regulatory strategy
Integrated CMC Strategy & Cost Optimization:
Strategic CMC decisions cascade across program lifecycle — early choices shape clinical timelines, manufacturing decisions affect commercial economics, and CMC team capacity determines execution velocity. We help integrate strategy, leadership, cost, and fundraising support — anchoring every decision to phase-appropriate program needs.
CMC Due Diligence
CMC issues identified late cost more than they should — failed comparability, scale-up surprises, oversized vectors, and regulatory pushback affect valuation, timelines, and program survival. We support investors and strategic partners across CMC due diligence and post-investment portfolio support — from pre-clinical through commercial-stage.
Technology & Platform Assessment:
AAV technology platform evaluation (capsid, production system, purification)
Vector design and engineering review
Vector manufacturability and potency risk assessment
Cell line and production system analysis
Manufacturing approach assessment (in-house vs. CDMO model)
Technology differentiation assessment vs. industry standards
Platform scalability evaluation
Process maturity review against program stage
Manufacturing & Operational Readiness:
Process development capability assessment
Manufacturing site readiness and inspection history review
CDMO relationship and risk assessment
Scale-up readiness assessment (clinical to commercial)
Comparability strategy evaluation for process changes
Long-term supply continuity evaluation
Program timeline review and milestone feasibility assessment
CMC organizational capability and team assessment
Regulatory & Quality Readiness:
CMC regulatory pathway strategy evaluation (pre-clinical onward)
Phase-appropriate regulatory and quality maturity assessment
IND/CTA quality and submission status review (when applicable)
BLA/MAA timeline projection analysis
GMP compliance and quality system assessment (when applicable)
Inspection readiness review for pre-approval (strategic assessment)
Analytical method portfolio review (available, planned, phase-appropriate, validation status)
CMC regulatory risk factor identification
Cost Economics & Investment Implications:
COGS modeling at current scale
Commercial-scale COGS projections
Industry benchmark comparison
Cost reduction opportunity assessment
Capital requirements for scale-up evaluation
Timeline impact on valuation review and advisory
Investment timing recommendations
Risk Assessment & Strategic Recommendations:
CMC risk matrix development with prioritization
Mitigation strategy recommendations
Stage-appropriate risk weighting (pre-clinical, clinical, commercial)
Site visit planning, observation, and reporting
Executive summary and board-level reporting
Post-investment portfolio improvement planning
Follow-up consultation and ongoing advisory support
Post-Investment & Portfolio Support:
Board observer or director service for portfolio company governance
Scientific Advisory Board (SAB) participation for portfolio companies
CMC advisory committee contribution for ongoing strategic input
Cross-portfolio CMC benchmarking and best-practice sharing
Periodic CMC briefings for investment team education
Follow-on round CMC due diligence (Series, IPO, M&A)
Industry trend and regulatory landscape monitoring for portfolio decisions
Integrated CMC Due Diligence:
CMC issues compound across program lifecycle — undetected pre-clinical risks (oversized vectors, suboptimal cell lines, manufacturing-incompatible designs) become expensive clinical-stage problems and existential commercial-stage challenges, threatening valuations, timelines, and program survival. We help integrate due diligence findings and post-investment portfolio support into actionable insights — anchored in independent assessment of program-specific risks and opportunities.
Ready to Discuss Your AAV Program?
Whether you are designing a vector, advancing CMC strategy and execution, optimizing a manufacturing process, building manufacturing and analytical capabilities, selecting a CDMO, or conducting technical due diligence, our services span the full AAV gene therapy CMC lifecycle — with deep expertise in each specific area, informed by direct experience across related domains.
Each engagement combines focused depth in your specific need with integrated insight across related CMC domains.