As development pipelines diversify and timelines compress, sponsors are under growing pressure to make better Chemistry, Manufacturing and Controls (CMC) decisions earlier … without inflating cost or risk.
Yet many programmes still follow a traditional segmented path and outsource drug substance (DS) and drug product (DP) activities to different vendors (often sequentially).
Although familiar, this model can introduce avoidable friction at the very point when speed, learning and alignment matter most.
Integrated outsourcing — when DS and DP activities are aligned within a single co-ordinated delivery model — is increasingly being adopted to simplify execution, accelerate timelines and strengthen CMC robustness.
Simon Wright, VP Business Development, Almac Pharma Services, and Simon Hamilton, VP Business Development, Almac Sciences, report.
Rather than treating the active pharmaceutical ingredient (API) and the finished dosage form as discrete hand-off stages, integration recognises their interdependence and manages them accordingly.
For manufacturers and sponsors alike, this represents a shift from linear execution to a more connected programme-led approach to development.
Why traditional DS–DP separation creates inefficiency
In a conventional development model, drug substance chemistry is progressed to a defined point, often with process and specification being “locked in,” before formulation and DP development truly begin.
Although this approach appears to be less risky, it often defers critical learning.
API attributes such as solid-state form, particle size distribution, morphology, residual solvent profile and impurity burden all influence downstream formulation behaviour.
When DP teams encounter challenges such as poor dissolution, content uniformity issues and physical instability, the levers available at that stage may be limited or too expensive to change.
Multiple outsourcing partners amplify this challenge. Separate contracts, quality systems, analytical strategies and project plans increase co-ordination overheads and slow decision-making.
Each transfer of material or data between vendors introduces delay and the potential for misalignment, often requiring additional studies or rework to reconcile differences.
Integrated outsourcing is designed to collapse these boundaries.
Integration as a development enabler, not just a procurement model
Effective integration is not simply about choosing a single supplier. Its value lies in how workstreams are planned, governed and executed together. In an integrated DS–DP model, API and formulation activities are designed to move in parallel when scientifically justified.
Early API material — produced to appropriate non-GMP or early-stage GMP standards — can be used to inform preformulation and formulation screening while process optimisation continues upstream.
Importantly, this is done within a common project framework with shared assumptions, risk registers and milestones.
This approach enables teams to ask different questions earlier:
- Are the chosen API solid-state form and particle attributes optimal for the intended dosage form?
- Do early formulation studies suggest the need for tighter (or more flexible) API controls?
- Can process choices upstream simplify DP manufacture, scale-up or downstream stability?
Rather than reacting to problems when they appear, integrated teams are positioned to anticipate and design around them.
Time savings through parallelisation and fewer hand-offs
One of the most tangible benefits of integrated outsourcing is time. Sequential development inherently builds waiting periods into a programme, such as waiting for the final API specification, waiting for release, waiting for data transfer and/or waiting for alignment amongst partners.
By contrast, integrated DS–DP programmes are structured to overlap critical activities while maintaining control.
Formulation scientists can work with API chemists to define “fit-for-purpose” material characteristics for early studies, rather than waiting for a finalised commercial route.
Analytical methods can be developed with both DS and DP matrices in mind, reducing duplication and late revalidation.
Overlapping API manufacture and DP development can recover weeks or months from early clinical timelines, even when programmes include pauses for sponsor decisions or dose optimisation.
The gains do not come from rushing tasks, but from removing organisational latency and ensuring that decisions are made with real‑time cross-functional input.
Improving decision quality at critical inflexion points
Speed alone is not the objective; better decisions are. Integrated outsourcing improves the quality of CMC decision-making at several inflexion points.
API physical properties and developability: When DS and DP teams collaborate closely, API physical properties are no longer treated as fixed outcomes but as design variables.
Adjustments to crystallisation conditions, salt form, milling strategy or isolation parameters can be evaluated in terms of their direct impact on formulation robustness and manufacturability.
Specification setting with downstream context: Integrated teams can set API specifications that are clinically and manufacturing-relevant, rather than generically conservative.
Excessively tight controls can drive unnecessary cost and failure risk; under-defined attributes can leave DP teams exposed. Integration allows justification to be built around real formulation performance data.
Analytical strategy alignment: Developing analytical methods with the full product lifecycle in mind helps to ensure continuity from early development through later-phase production.
Stability-indicating methods, impurity tracking and dissolution testing strategies benefit from being designed within a single analytical philosophy rather than harmonised retrospectively.
Managing risk earlier rather than later
Parallel development is sometimes perceived as a high-risk activity because issues discovered in one area may affect work underway elsewhere.
In practice, integrated programmes often reduce overall risk by shifting discovery earlier … when changes are still manageable.
Late-stage CMC changes are among the most costly and disruptive events in development, triggering revalidation, stability resets or regulatory delays.
Integrated outsourcing reduces the likelihood of such events by ensuring DS and DP risks are surfaced, discussed and mitigated while retaining flexibility. Shared governance structures play an important role here.
Regular integrated reviews, common risk registers and transparent decision-making ensure that trade-offs are understood and agreed collectively, rather than emerging as surprises during transfer or scale-up.
Impact beyond early development
Although the benefits of integration are often discussed in the context of IND or first-in-human acceleration, the value extends into later phases.
Programmes developed with integrated thinking tend to exhibit greater robustness during scale-up and commercial preparation.
Knowledge continuity — from early physical chemistry decisions through to DP manufacture — reduces the risk of late-emerging constraints.
Operating under aligned systems and documentation standards also simplifies regulatory interactions and audit readiness as programmes mature.
As development progresses, the cost of change rises sharply. Integrated outsourcing seeks to invest effort earlier so that later phases proceed more predictably.
What to look for in an integrated outsourcing partner
For sponsors considering this approach, several practical factors distinguish meaningful integration from simple service aggregation:
- single project ownership with authority across DS, DP and analytics
- evidence of parallel execution, not just the colocation of services
- structured governance enabling rapid, cross-functional decisions
- clear strategy for API physical attributes and DP manufacturability.
Integration works best when it is embedded in how programmes are run, not added as an overlay.
A strategic shift in CMC execution
As modalities become more complex and investor expectations intensify, being able to execute CMC programmes efficiently and intelligently is a competitive differentiator.
The integrated outsourcing of DS and DP offers a pragmatic way to reduce friction, improve learning and accelerate progress without compromising scientific rigour.
For manufacturers, it represents an evolution from task-based service provision to programme-level partnership.
For sponsors, it aligns speed with robustness and turns CMC from a bottleneck into a strategic asset.