Case studies

Background

A biotech developing an autologous CAR-T cell therapy was preparing to enter Phase 2 and needed to move from 4 to 12 batches per month within 12 months. The increase had to arrive without interrupting GMP compliance or clinical supply, which meant capacity, staffing, documentation and the regulatory filing all had to land inside the same window.

Approach

• Evaluated hotel manufacturing partners against the two criteria that decide a 12-month timeline: existing autologous cell therapy experience, and operational readiness to take the process without a long qualification runway
• Adjusted cleanroom layout and personnel and material flow, executed equipment qualification, and oversaw Grade B validation
• Recruited and onboarded a 10-person manufacturing and MSAT team spanning director level to operators
• Deployed a fully electronic batch record system and authored the SOP and quality documentation suite behind it, so the documentation existed before the team scaled rather than after
• Managed the tech transfer end to end, covering analytical method transfer, raw material sourcing and process comparability, and carried it through to the IND amendment submission

Capacity tripled. 4 to 12 batches per month, validated and GMP-ready

End-to-end execution in 12 months. Partner selection through IND amendment submission, inside the original window

IND amendment submitted on time. Clinical dosing continued without interruption through the transition, and Phase 2 enrolment was not held up by manufacturing

Background

A seed-stage biotech developing an autologous T cell therapy came to us during fundraising with no internal CMC function. It needed a milestone-driven plan covering both the US and Canada, sequenced so that each block of work could be paid for by the round preceding it rather than assuming capital that had not yet been raised.

Approach

• Designed a phased preclinical validation strategy built around a Pre-pre-CTA meeting with Health Canada and an INTERACT meeting with FDA, so that agency feedback arrived before the expensive work started rather than after it
• Established a process development framework for the R&D to GMP transition and defined the analytical methods needed for product characterization and release
• Mapped CDMO transition requirements and produced an early shortlist, since partner capability constrains process design and is cheaper to establish while the process is still changeable
• Assessed investor and clinical timelines against each other and restructured the activity list into funding-phase-aligned priorities

CMC and regulatory foundation delivered for the raise. The plan gave the fundraise a defensible technical basis rather than a timeline assertion

CDMO shortlist produced early. Process scalability and GMP readiness assessed while the process could still be adapted to the partner

Milestone-to-milestone execution plan delivered. Internal team and external partners working from one sequence

Background

An academic CAR-T spinout at early preclinical stage had no quality framework and a team trained in academia rather than GMP. It needed a QMS foundation that would support structured development and stand up to investor and partner scrutiny, without paying for specialized software or infrastructure the company would not use for several years.

Approach

• Designed and deployed document control, training management, change control, supplier management and a risk management framework
• Authored and implemented over 100 SOPs, policies, templates, forms and checklists, written for a team with no prior GMP exposure
• Configured SharePoint with automated workflows for document review, approval and training assignment, which gave the company version control and auditable training records without a licensed QMS platform
• Ran a change management program alongside the build, aimed at how the team actually worked rather than only at the document set. A quality system the team treats as an obstacle produces records that will not hold up under scrutiny

Operational QMS delivered in 6 months. Document control, training, change control, supplier management and risk management all live

Built to scale with the company. The structure carries through IND-enabling studies without a rebuild

Investor and partner diligence supported. The company could show a working quality system rather than an intention to build one

Background

Across several engagements, sponsors at different stages of development, from early programs heading into Phase 1 to programs in late-stage trials, each needed a CDMO with relevant modality experience, a credible scale-up path and compliance across North American jurisdictions. In each case the shortlisted candidates claimed all three, so the selection had to rest on evidence rather than on capability decks.

Approach

• Screened candidate CDMOs on modality-specific experience, GMP readiness and analytical capability
• Issued structured RFPs covering manufacturing process fit, cost structure, tech transfer feasibility, quality systems and timeline alignment
• Distributed capability questionnaires and ran reference checks with companies that had already worked with the shortlisted candidates, which is where the gap between claimed and actual capability tends to show
• Arranged on-site visits and supported the final contract negotiations

A partner selected for each client. Technical, regulatory and operational requirements assessed against evidence rather than claims

Exposure reduced before commitment. Site visits and reference checks surfaced capability gaps while switching candidates was still cheap

Scale-up path assessed. Each selection weighed the partner's capacity from the client's current phase through to commercial supply

Background

A Series A allogeneic T cell therapy company in an autoimmune indication needed a per-patient COGs analysis it could put in front of a board. Dosing regimen and manufacturing yield were both unsettled at that stage, so a single point estimate would have been misleading. The model had to carry that uncertainty explicitly.

Approach

• Built a scenario framework across low and high dose treatment strategies and low and high yield manufacturing assumptions, so the output is a range with named drivers rather than a single figure
• Developed a per-patient cost breakdown covering raw materials, labor, facility overhead, QC and release testing, cold chain, licensing fees and clinical costs
• Integrated real CDMO pricing rather than list rates or published benchmarks
• Delivered the model in a form the client can update directly, since most inputs at Series A are provisional and will move as the program generates data

Roughly 5× lower cost per patient than comparable autologous products under the modeled scenarios. The figure is scenario-dependent and moves with the yield assumption, which the model states rather than hides

Board-ready analysis delivered. One financial framework supporting both investment and manufacturing decisions

Model built for revision. Structured so inputs can be replaced as the program generates real cost data

Background

A clinical-stage CAR-T biotech moving from bags to a bioreactor hit post-harvest viability loss that had not appeared in the original platform, alongside increased apoptosis and signs of excessive activation and possible exhaustion. Phase 2 IND amendment submission depended on resolving it, so the investigation had to establish cause rather than find a workaround that would not survive later scrutiny.

Approach

• Investigated oxygenation gradients and pH stability as sources of cellular stress, and adjusted setpoints
• Compared media formulation and cytokine cocktail against the bag process, identified the ratios driving overactivation, and adjusted them
• Modified the media exchange and resuspension schedule to improve cell health across the expansion cycle
• Ran a structured comparability study across both platforms to confirm the findings held, and iterated until viability and functional markers reached acceptable thresholds

Viability restored to the acceptable range, with improved run-to-run consistency

IND amendment submitted. Phase 2 regulatory milestone reached on the revised process

Process better controlled at scale. Root cause was identified rather than compensated for, which leaves the process characterized for later phases

Background

A CAR-T program was manufacturing a new GMP batch of lentiviral vector to supply two clinical trials. The manufacturing site would execute the sponsor's plan but not define it, and the sponsor had no internal CMC function, which left release testing, stability design and specification setting without an owner. Historical data covered 3 to 5 runs over 8 years.

Approach

• Mapped the assay panel against phase-appropriate expectations and identified gaps in residual plasmid DNA, host cell protein and sub-visible particulates
• Designed a 48-month stability program and a 200-vial sampling plan across release, stability and retains
• Justified "to report" acceptance criteria where historical data could not support statistical limits
• Reviewed deviations against the quality agreement and escalated a stalled method validation to the testing laboratory's senior leadership

Release and stability programs defined. Phase-appropriate scope agreed across sponsor, manufacturing site and testing laboratories

Specification and sampling plan issued. 200 vials allocated across release, stability and retains

Four-month analytical delay recovered in 24 hours. Direct escalation restored the original release testing window

Background

The client's bioreactor platform was established in regenerative medicine but had no T cell data. Entering autologous CAR-T meant showing measurable advantage over an incumbent static system that is simpler to run, cheaper per consumable and already embedded in clinical processes.

Approach

• Replaced exploratory testing with a DOE across seeding density and agitation speed, benchmarked against the incumbent static system
• Extended the readout from expansion to phenotype, exhaustion markers and functional potency
• Sourced a preclinical lentiviral vector and fixed the transduction condition with the supplier before the study opened
• Consolidated two overlapping vendor testing proposals into one integrated testing plan

Decision-grade evaluation framework in place. Results interpretable against a real market comparator

Three development runs and four paired comparisons completed against a static control

Multi-partner data package under execution. Development partner, analytical partner and vector supplier aligned on one testing plan

Background

The client's platform worked well for research workflows but had been designed around cell lines and laboratory records rather than primary cells and GMP batch records. Selling into cell therapy manufacturing meant meeting the traceability and data integrity expectations of a real batch record.

Approach

• Rebuilt an executed batch record of more than 110 steps inside the platform to surface failure modes a demonstration dataset would miss
• Specified around 35 GMP requirements across four reports, including step timestamps, electronic signatures, hold timers and in-record calculations
• Recommended a data model supporting many-to-many donor and patient relationships for autologous and allogeneic products
• Assessed the patient data architecture and supported a siloed subject registry linked by non-identifying subject ID

Around 35 GMP requirements specified and accepted into the product roadmap

Data model redesigned. Adopted to support both autologous and allogeneic traceability

Reference batch record delivered. A redacted 110-step record for internal development and testing use

Background

The client's platform drew interest but not orders. Prospects on an established closed system saw the comparability burden and the risk of moving first, and stayed with the incumbent. Lifting that constraint required a reusable comparability package the client could put in front of a prospect's CMC lead.

Approach

• Completed a Canadian regulatory assessment, including how FDA-facing documentation can be adapted for Health Canada
• Built a platform comparison matrix that doubles as a gap assessment for both systems
• Mapped process parameters on both platforms to the quality attributes regulators will examine
• Wrote a tiered comparability protocol and DOE framework anchored to ICH Q5E, Q9 and Q10, with a plain-language handbook for small teams

Five-part comparability package delivered. Platform matrix, CPP/CQA linkage, comparability protocol, DOE framework and client handbook

Canadian regulatory assessment completed. With a documented adaptation path from existing FDA-facing material

Reusable across the prospect base. Modular documents selected per conversation rather than rebuilt each time

Background

A senior executive was evaluating an investment in a company combining an autologous TCR-T against a solid tumor antigen with a T cell engager that had shown safety but no monotherapy efficacy in two Phase 2 trials. The decision needed an independent read on whether the preclinical package supported the plan.

Approach

• Benchmarked the preclinical efficacy data against comparable programs, which showed tumor maintenance rather than clearance
• Tested the claimed 85% TCR-T dose reduction against clinical precedent from similar extrapolations
• Assessed the two-arm trial design as a direct read on the engager's contribution
• Built a CMC question set for the meeting with the chief technology officer, covering process details absent from the corporate materials

Independent assessment delivered inside the decision window, with written notes rather than a verbal opinion

Preclinical and dosing risks documented against named comparators

CMC question set delivered for the meeting with the chief technology officer

Background

The client was building a company around a targeted lentiviral vector for in vivo CAR delivery, with the science coming from an academic group and the vector engineering contracted to a specialist CRO. It had no internal function to hold the CRO to a plan or to look past the discovery screen toward manufacture.

Approach

• Defined five workstreams spanning screening support, product stability, vector design, scale-up planning and the CAR packaging constraint
• Separated the discovery screen from the scale program so early choices would not foreclose manufacturing options
• Reviewed the CRO agreement before signature, flagging license terms, manufacturing incentives, embedded reagent licenses and the missing statement of work
• Contributed to a two-phase construct design and to WPRE variant testing with the eventual regulatory submission in mind

Screen and scale separated. Discovery work and the manufacturing path resourced as distinct programs

CRO agreement risks documented before signature. Raised with the client's leadership

Construct design set. Two-phase design with WPRE variants built in