Many small-molecule programs fail to progress beyond Phase I. In many cases, this is not because the molecule or target biology is fundamentally wrong, but because the formulation never enabled a fair test of the biology.
Insufficient exposure, variable bioavailability, or release profiles misaligned with the disease mechanism or the target product profile (TPP) frequently prevent meaningful pharmacodynamic interpretation. Once clinical studies begin, correcting these limitations is often difficult, slow, and expensive.
Formulation decisions made early therefore set clinical and lifecycle risk.
In early development, CMC risk is often framed around timelines and execution. In practice, however, the highest-impact risks are introduced before GMP execution begins, during:
Solid-form selection
Biopharmaceutic assessment
Early formulation design
These decisions directly influence:
Achievable exposure
Dose flexibility
Clinical interpretability
Scalability and late-stage viability
At Crystal Pharmatech, we view early-stage CMC success as a function of decision quality, not throughput.
First-Time-Right formulation is not about optimizing speed to first-in-human. It is about designing formulation strategies that remain valid as programs advance.
At Crystal Pharmatech, solid-state research, polymorph/salt/cocrystal screening and selection, preformulation, crystallization, and formulation development are designed as one integrated scientific system.
In practice, this means:
Formulation strategies are tailored to disease-relevant exposure, not just manufacturability
Release profiles are aligned with the therapeutic mechanism and clinical hypothesis
Phase I formulations are evaluated against Phase II+ expectations, not treated as disposable solutions
Early formulation choices are made to minimize disruptive reformulation later in development
The objective is to preserve clinical momentum while reducing downstream technical and regulatory risk.
Crystal's formulation strategy is guided by the M3 framework, which integrates formulation decisions across three interdependent dimensions:
Molecule Clinical needs, DMPK understanding, pharmacodynamics, safety, and the molecular profile define what exposure is required to meaningfully test the biology.
Material API solid form, physicochemical and biopharmaceutical properties, excipient functionality, stability, and process-fit composition determine whether that exposure can be delivered reliably and reproducibly.
Medicine TPP-driven design, critical quality attributes (CQAs), critical process parameters (CPPs), and a durable drug product control strategy ensure that the formulation can scale and remain viable across development stages.
Formulation decisions are evaluated across all three dimensions simultaneously—not optimized in isolation.
Crystal Pharmatech operates as a specialty CRO/CDMO, intentionally focused on the most decision-intensive stages of development.
Rather than offering maximal service breadth, we concentrate depth and senior scientific oversight in areas where early decisions disproportionately influence clinical success.
This specialization allows us to:
Go deeper where risk is created
Maintain consistent scientific ownership of formulation strategy
Support programs before scale and execution dominate decision-making
Crystal often complements one-stop-shop CDMOs by helping ensure that formulation foundations are correct before programs enter execution-heavy phases.
Solid-state research, polymorph/salt/cocrystal screening and selection, preformulation, and crystallization development are supported from Cranbury, New Jersey or Suzhou, China. Formulation development and GMP manufacturing are supported from Toronto, Canada or Suzhou, China.
Our geographic footprint provides flexibility in execution and supply strategy, while maintaining consistent scientific assumptions and lifecycle intent.
The science does not change with location.
Crystal Pharmatech is typically engaged when teams want to:
Pressure-test whether early formulation strategies can survive beyond Phase I
Align solid-state and formulation decisions with clinical objectives and TPP
Reduce the risk of late-stage reformulation or clinical ambiguity
Bring senior formulation judgment into early development decisions
First-Time-Right formulation is ultimately about respecting the cost of early decisions.
When formulation is designed with full lifecycle intent—grounded in Molecule, Material, and Medicine—programs are better positioned to generate interpretable clinical data and progress with confidence.
Subscribe to be the first to get the updates!
