Dynamics Reshaping Expectations for CMC Strategy and Execution

As the core regulatory and technical framework in drug development, Chemistry, Manufacturing, and Controls (CMC) supports regulatory approval, safety and commercial scalability. It accounts for the active pharmaceutical ingredient (API), drug formulation, and manufacturing controls required for global regulatory filings. CMC also validates that small-batch lab processes can be safely scaled to commercial manufacturing without altering the drug’s properties.

In today’s drug development landscape, minimizing the time between molecule batch and finished drug product, AI-assisted development support, phase-appropriate and small-batch supply strategies, and greater demand for expert guidance across development are among the key trends in CMC.

Experienced CDMOs and CROs can help identify technical and regulatory risks early, evaluate alternative development pathways, and support decisions that improve development efficiency, reduce downstream risk, and help sponsors reach critical milestones with greater confidence.

Kevin Kane, PhD, CMC Strategy Director, PPD Strategic Scientific Solutions (S3), Thermo Fisher Scientific, shares insight on the dynamics reshaping expectations for CMC strategy and execution. 

Contract Pharma: What industry trends are having the most impact on the CMC landscape?

Kevin Kane: Sponsors today are operating in an environment defined by increasing molecule complexity, tighter funding conditions, and pressure to reach value inflection points more quickly. These dynamics are reshaping expectations for CMC strategy and execution. Across today’s development environment, clinical, CMC, manufacturing, and supply decisions are increasingly interconnected, making coordination and adaptability critical to success.

Trends we see include minimizing the time between molecule batch and finished drug product or clinic-ready supply, AI-assisted development support, phase-appropriate and small-batch supply strategies, and greater demand for expert guidance across development activities. From a CMC perspective, sponsors are seeking efficiency while maximizing the value of internal and external investment. Reduced costs alone do not create value. Sponsors need partners that bring expertise, quality, and an understanding of how CMC decisions affect broader clinical and business objectives.

AI in drug development provides both promise and risk. Applications include formulation optimization, analysis of large datasets, stability prediction, packaging selection, and root-cause analysis. However, AI cannot replace scientific judgment or practical expertise in chemistry, biology, engineering, and pharmacology. Its greatest value comes from supporting better technical and regulatory decision-making and helping sponsors make more informed development choices.

Contract Pharma: What does CMC entail at each stage of drug development (preclinical, clinical, commercial) and why is it important to start early?

Kevin Kane: Pushing from flask to API to drug prototype to preclinical studies to clinical supply is the linear development timeline most CMC programs are built upon, but CMC strategy begins much earlier by defining what success should look like later in development. Because clinical, nonclinical, and CMC decisions continuously inform one another, CMC strategy should not be viewed as a standalone workstream. Early planning helps ensure development activities remain aligned with evolving clinical objectives and emerging data.

Every development effort should start with key questions about the target patient population, intended therapeutic benefit, and how the target product profile may evolve as new data emerge. Clinical objectives determine what must be studied in the nonclinical setting, which in turn shapes CMC requirements for drug substance and drug product development. As data emerge, CMC activities help inform smarter decisions regarding dose selection, formulation, and delivery approaches.

One common challenge is that products supplied to the clinic are sometimes suboptimal because critical product attributes were fixed too early and not reassessed as clinical understanding evolved. This highlights the importance of ongoing collaboration between clinical and CMC teams, supported by exploratory studies and access to multiple formulation or delivery options. As clinical knowledge advances, sponsors should be prepared to refine drug substance and drug product strategies. Updates to the CMC sections of an IND are a routine and expected part of development as product requirements become better understood.

Contract Pharma: What are best practices for CMC strategy development?

Kevin Kane: While CMC teams focus on the technical details of drug substance and product development, effective CMC strategy is informed by experience, risk anticipation, and development objectives. For sponsors working with CDMO partners, a clear understanding of roles and responsibilities is essential.

Sponsors retain responsibility for the overall development strategy, including supply planning, investment decisions, and long-term program objectives. Experienced CDMOs can help identify technical and regulatory risks early, evaluate alternative development pathways, and support decisions that improve development efficiency, reduce downstream risk, and help sponsors reach critical milestones with greater confidence.

Additionally, CMC strategy should prioritize phase-appropriate requirements, incorporate contingency planning, and maintain a roadmap for future product improvements. Effective strategists stay informed about emerging capabilities, vendor changes, and future risks that could affect development. This enables faster and more informed responses when clinical outcomes, manufacturing needs, or supply requirements change.

Contract Pharma: What are the considerations for biologics vs. small molecules?

Kevin Kane: One of the most important distinctions is that process changes can alter the biologic product itself, whereas small molecule development is typically driven more by chemistry, formulation performance, scalability, and supply chain considerations. This difference shapes development priorities, risk profiles, and regulatory expectations throughout development.

Both biologics and small molecules require extensive characterization of physicochemical properties from the earliest stages of development. Changes to expression systems, purification methods, synthesis routes, formulations, or manufacturing processes can influence product quality and performance. Maintaining a clear record of changes and their impact helps ensure alignment between CMC activities and nonclinical findings.

For biologics, process knowledge and product characterization are particularly important because manufacturing changes can directly affect the product. For small molecules, considerations such as purity, solubility, dissolution, formulation performance, scalability, and supply chain robustness often play a larger role in development strategy.

Contract Pharma: What are some common misconceptions around CMC strategy that cause downstream issues?

Kevin Kane: A common misconception is that CMC strategy commits a program to its initial target product profile. This can result in retaining a phase-appropriate but ultimately non-scalable formulation or overinvesting in product development before the molecule has demonstrated sufficient clinical potential.

Another misconception is that any change to drug substance or drug product automatically requires additional clinical studies. In reality, clinical surprises and subsequent product adjustments are often part of development. Resisting changes in response to emerging data can be counterproductive.

Effective CMC strategy anticipates that product requirements may evolve as clinical knowledge grows. Sponsors sometimes focus heavily on the cost of changing course while underestimating the much larger consequences of clinical failure or suboptimal product performance. Ultimately, effective CMC strategy is not simply about technical execution. It is about protecting asset value, improving development efficiency, and ensuring resources are allocated to activities that meaningfully reduce program risk.

Contract Pharma: What’s the importance of a shared planning and decision framework for clinical strategy, CMC, manufacturing readiness, and supply forecasting?

Kevin Kane: A shared planning and decision framework is essential because clinical strategy, CMC development, manufacturing readiness, and supply forecasting are highly interdependent activities that evolve as new data emerge. Clinical outcomes influence product specifications, dosing strategies, patient populations, and regulatory requirements, all of which can affect manufacturing and supply needs.

CMC planning that follows a purely linear path based on fixed assumptions can create costly misalignment as programs evolve. A shared framework helps ensure that clinical, regulatory, manufacturing, and business objectives remain connected throughout development.

Greater coordination across clinical development, CMC, manufacturing, and supply planning can improve development efficiency by reducing communication gaps, accelerating information sharing, and enabling faster cross-functional decision-making. Whether achieved through integrated operating models or strong collaboration across partners, the goal is to ensure that emerging clinical insights can be translated quickly into manufacturing and supply decisions.

The greatest benefits are realized when sponsors and partners operate within a shared strategic framework that includes clear decision milestones, cross-functional review of emerging data, and flexibility to adapt plans as evidence evolves. This helps reduce development risk, improve resource utilization, and increase the likelihood of advancing the right product with the right investment at the right time.

As development programs become more complex, sponsors increasingly benefit from a coordinated approach that connects clinical strategy, CMC, manufacturing, and supply planning. Thermo Fisher Scientific’s Strategic Scientific Solutions team helps customers navigate these interdependencies through strategic consulting and development planning designed to reduce risk and support informed decision-making throughout the development journey. Learn more about the full scope of services within our Accelerator™ Drug Development platform.