In the first post in this series, we looked at the manufacturing landscape for advanced therapies and what the FDA data tells us about why CMC strategy is so consequential to regulatory outcomes. Early manufacturing investment in a program is not a nice-to-have. It is one of the highest-leverage decisions a program leader makes.
This post moves from landscape to evaluation. We start with the first and most important criterion in any CDMO assessment, modality-specific expertise, and then look at the structural feature that most reliably distinguishes the strongest development partners from the rest of the field: integration across process development, analytical development, and GMP manufacturing.
A CDMO's overall capability profile, the facility size, ISO classifications, number of GMP suites, and client roster tell you something. But it does not tell you whether the scientists who would work on your program understand your biology. That distinction is where evaluations tend to fall apart, and where the most consequential differences between CDMOs become visible.
1. Modality-Specific Expertise: Matching Capability to Your Biology
Advanced therapy manufacturing is not a single discipline. The expertise required to develop and manufacture a CAR-T cell therapy differs substantially from what is needed for an MSC program, a viral vector, or an iPSC-derived product. Process conditions, critical quality attributes, analytical requirements, and regulatory considerations vary meaningfully across these modalities, and experience in one does not automatically translate to competence in another.
When evaluating CDMOs, direct experience with your specific modality is among the most important criteria to assess. This means experience that is scientific and operational, not just commercial. A CDMO that has listed your modality in their capabilities but lacks scientists who have navigated its technical complexity will struggle to be a genuine development partner when challenges arise. And in advanced therapy development, challenges always arise.
Stem cell programs illustrate why this matters. MSC and iPSC-derived products are among the most process-sensitive therapies in development. Identity, potency, and safety are all tightly coupled to process conditions, meaning that a CDMO's depth of biological understanding will directly influence the quality of decisions made at every stage, from vessel selection and media formulation through scale-up strategy and lot release testing.
"A CDMO with genuine depth in your modality will engage your questions with specificity and enthusiasm, drawing on real program experience rather than describing general manufacturing capabilities."
2. Productive Questions for Surfacing Modality Expertise
The following questions are designed to surface whether a CDMO has genuine depth in your modality or is extending a general manufacturing capability into a space where their scientific experience is more limited.
Program experience: What programs in this specific modality has your team taken from process development through GMP manufacturing? The answer you are looking for is specific: named program types, key process challenges encountered, how they were resolved, and what the team learned. General statements about capability without specific program experience should be weighted accordingly.
Regulatory outcomes: Have you supported IND filings in this modality? What does your CMC track record look like? Regulatory experience in your modality demonstrates scientific depth. A CDMO that has taken programs through the IND process understands what the FDA looks for and how to build a CMC package that holds up under review.
Scientific depth: What are the most technically challenging aspects of this biology, and how does your team approach them? This is the question that most reliably distinguishes genuine expertise from described capability. Scientists who know your biology will engage this question with specificity and with the kind of candor that comes from having worked through real problems.
Pay attention not just to what the CDMO says, but how they say it. Genuine expertise has a texture: specific examples, acknowledgment that the science is still evolving, and clear reasoning about trade-offs. The absence of that texture is informative.
3. Integration Across Process Development, Analytics, and GMP
One of the clearest structural differentiators between CDMO partners is whether process development, analytical development, and GMP manufacturing operate as a genuinely integrated team, or as sequential handoffs between separate groups.
In the handoff model, process development builds and documents the process, then transfers it to an analytical team that develops the assays, which then transfers the package to GMP for execution. At each transition, institutional knowledge is compressed into documentation, and the scientists who developed the process become less available. When questions arise during GMP execution, the team that runs the manufacturing run may not have full visibility into why certain decisions were made.
In an integrated model, these functions work together from the start. The analytical scientists who develop release assays are informed by process development data as it is generated. The GMP team participates in late-stage process development so that manufacturing execution is informed by direct experience, not only documentation. And when technical questions arise during clinical runs, the scientists with the deepest process knowledge are already part of the team.
"Integration does not simplify the science. It means the full complexity is visible and managed from the start, with the right people already informed."
The implications for program outcomes are significant. Integrated development produces more robust processes because the people asking the analytical questions are the same people who understand the process. It produces faster timelines because the iterative loop between process development and analytical development is compressed. And it produces stronger GMP execution because the team has continuity from development through clinical manufacturing.
4. What to Look for in an Integrated CDMO Model
When evaluating a CDMO's integration model, look for evidence rather than description. A few indicators worth probing:
Signs of Genuine Integration
- The scientists who developed the process are still engaged through GMP execution, not just available for questions.
- Assay development timelines are explicitly aligned with process development milestones, not treated as sequential.
- GMP staff participate in late-stage development activities, so execution is informed by direct experience.
- Technical questions during manufacturing runs go directly to the development scientists, not through a project management layer.
- The program team you meet during evaluation is the team that would run your program.
That last point is worth emphasizing. The scientists who participate in your evaluation conversations should be representative of the team that would work on your program, not a presentation team assembled for business development purposes. The quality of that scientific conversation is among the most useful data points in the entire evaluation.
Landmark Bio is built around the integrated model. Process development, analytical development, QC, and GMP manufacturing are staffed as a unified team. The scientists who design a process are the same ones who see it through to GMP scale.
5. Assessing Integration During the Evaluation
Ask the CDMO to walk you through how a program moves from process development to GMP execution. Listen to how they describe the transitions. Do they describe them as handoffs or as a continuous process with the same core team? Do they describe cases where analytical development and process development ran in parallel, and how they coordinated? Do GMP scientists participate in that explanation, or only the project lead?
The most revealing question on integration is often a simple one: who is in the room when a technical question arises during a GMP run, and how does that work? The answer tells you a great deal about whether the CDMO's integration model is structural or aspirational.
Looking Ahead
Modality expertise and development integration are the two criteria that most reliably separate translational development partners from contract manufacturers. They are necessary conditions for the kind of partnership that produces strong programs. They are not sufficient on their own.
In the next post, we go deeper into the criteria that determine whether your first GMP run executes reliably and whether your IND package holds up under review: process development philosophy, materials strategy, and facility and quality readiness. These are the operational dimensions where a CDMO's development-forward thinking, or its absence, becomes visible at scale.
COMING NEXT IN THIS SERIES
Part 3: Process Philosophy, Materials Strategy, and Facility Readiness
How a development-forward approach builds the foundation for successful GMP execution, and what to look for in facility infrastructure and quality systems.
.png)
