Why CMC is the Most Underestimated Function in Drug Development

How chemistry, manufacturing and controls impacts regulatory approval, timelines and risk in drug development

CMC in drug development refers to chemistry, manufacturing and controls, the technical and regulatory work that proves a drug can be manufactured safely, consistently and at the required quality standard. It covers the drug substance, production process, analytical testing, quality controls and regulatory data needed to support clinical trials, approval and post-approval changes.

 

Key takeaways

• CMC stands for chemistry, manufacturing and controls.
• In drug development, CMC proves that a product can be manufactured safely, consistently and at scale.
• CMC requirements increase from preclinical development through Phase III, approval and post-approval lifecycle management.
• Common CMC gaps include weak analytical validation, incomplete stability data, poor process validation and insufficient regulatory CMC expertise.
• The deepest CMC talent gaps are often in process development, regulatory CMC, MSAT and analytical development.

 

Seventy-four percent of complete response letters (CRLs) issued by the FDA between 2020 and 2024 cited quality and manufacturing deficiencies, based on an independent industry analysis of more than 200 CRLs published in 2025. That figure should give pause to any organisation that treats chemistry, manufacturing and controls as a downstream concern. 

CMC failures remain one of the most predictable and preventable causes of regulatory delay, yet the function is systematically underestimated across the pharmaceutical and biotech industry.

Clinical development continues to command the majority of attention and investment, yet CMC ultimately determines whether a promising molecule can actually be manufactured consistently, safely and at scale. For many organisations, it takes a regulatory setback to bring that reality into focus. Without a mature CMC strategy, clinical progress can outpace the technical evidence needed for approval.

 

What does CMC stand for in Pharma and Biotech?

CMC stands for chemistry, manufacturing and controls. In pharma and biotech, CMC is the technical and regulatory function responsible for proving that a drug can be made consistently, safely and in line with regulatory quality standards.

Often described as the technical backbone of drug development, CMC covers the full body of work required to develop, manufacture and test a drug product to the standard global regulators require.

In biotech, CMC can be especially complex because biologics, cell and gene therapies and other advanced modalities often require more sensitive manufacturing processes, stricter analytical controls and more detailed comparability data than traditional small molecule products.

CMC readiness is a prerequisite for clinical and commercial progression, because each component depends on the others to demonstrate that a product can be made safely and reliably. In practice, it is the function that determines whether a scientific concept can be translated into a reproducible and approvable product.

Chemistry

The drug substance itself. 

Its molecular structure, physical and chemical properties, production route, impurity profile and stability characteristics. Understanding the chemistry of a product is the foundation on which everything else is built. This includes defining critical quality attributes (CQAs), identifying potential impurities early, and establishing the analytical framework that supports later-stage development.

Manufacturing

How the drug is produced at scale. 

This spans process development, technology transfer, scale-up operations and GMP-compliant production. Manufacturing is where science meets commercial reality and where robustness, reproducibility and scalability must be proven, long before regulators assess commercial readiness.

Controls

The analytical and quality systems that prove compliance.

Controls ensure every batch meets specifications for identity, strength, purity and quality. They provide the evidence base underpinning regulatory submissions, comparability exercises, stability commitments and ongoing lifecycle management.

Together they form the technical backbone of every regulatory submission. Global agencies including the FDA, EMA and PMDA require comprehensive and increasingly rigorous CMC regulatory data at every stage, from first-in-human studies through to post-approval change management.

 

How CMC analytical development impacts drug approval

Analytical development is central to CMC because it provides the evidence regulators use to assess product quality, consistency and stability. Without validated analytical methods, sponsors may struggle to prove that batches meet required specifications or that manufacturing changes do not affect the safety, strength or purity of the product.

In practice, weak analytical development can delay approval by creating gaps in stability data, impurity testing, comparability evidence or batch release controls. This is why analytical development needs to mature alongside process development, rather than being treated as a late-stage quality exercise.

 

The cost of getting CMC wrong

CMC problems do not announce themselves early. They surface at the worst possible moments, during a Phase III validation campaign, ahead of a pre-approval inspection or buried in a complete response letter that arrives after years of development investment.

The organisations most exposed are not always those lacking scientific talent. A process development gap at Phase I is often recoverable. At Phase III, with process validation timelines locked and manufacturing sites under scrutiny, the same gap can add months to a programme and significant cost to an already stretched budget.

Inadequate pharmaceutical development, poor drug product controls, stability deficiencies and GMP-related findings are among the most consistently cited reasons for complete response letters across NDA and BLA submissions. These are not novel findings. In most cases, they trace back to the same root cause: CMC capability that was not in place when it was needed most.

 

How CMC requirements evolve across the drug development lifecycle

CMC requirements follow a predictable regulatory timeline, but the depth of data expected increases sharply at each stage. CMC is not a fixed function. Its requirements vary across the development lifecycle, and the expertise needed to support each stage develops in line with those demands.

At a high level, CMC priorities typically shift as follows:

Stage	Main CMC priority	Common risk if delayed
Preclinical / IND-enabling	Drug substance characterisation, initial formulation, analytical method development	Weak IND package or insufficient early technical data
Phase I / II	GMP manufacturing, batch consistency, method validation, formulation refinement	Data gaps carried into later-stage development
Phase III / pre-approval	Process validation, stability data, commercial manufacturing readiness	Submission delays, inspection findings or CRL risk
Post-approval	Change control, lifecycle management, site changes, formulation updates	Regulatory re-engagement delays or supply disruption

Preclinical and IND-enabling

The focus is on characterising the drug substance, developing initial formulations and building the analytical methods needed to support toxicology studies. The goal is generating enough CMC data to support an IND application and demonstrate the drug is safe for first-in-human studies.

Phase I and Phase II

Manufacturing processes must be GMP-compliant, batches consistent and traceable, and analytical methods validated to support data integrity. Formulation work continues in parallel, with a focus on identifying the optimal drug product for later-stage development. Regular agency engagement during this period is strongly encouraged to avoid late-stage surprises. At this stage, gaps most often emerge in analytical validation and process consistency, which can limit the reliability of data carried forward into later phases.

Phase III and pre-approval

By Phase III, the demands on CMC teams intensify significantly. Process validation must be complete, long-term stability studies finalised and the CMC sections of the marketing application ready for submission. The End of Phase II meeting is a critical checkpoint that sets the tone for everything that follows. Organisations that arrive at it without the right CMC capability already in place rarely have enough time to course correct. At this point, incomplete process validation or insufficient stability data can directly delay submission timelines or result in regulatory findings.

Late-stage CMC development is where earlier technical decisions are stress-tested against regulatory expectations. By Phase III, sponsors need validated processes, robust analytical methods, long-term stability data, inspection-ready manufacturing sites and a clear regulatory CMC strategy.

Post-approval: approval is not the finish line

Approval is not the finish line for CMC. Manufacturing site changes, process improvements, formulation adjustments and product lifecycle extensions all require ongoing regulatory management. It is one of the most consistently understaffed phases in the development lifecycle, and organisations that deprioritise it often find themselves unprepared when post-approval changes require regulatory re-engagement.

 

The functions within CMC and where the talent gaps are deepest

CMC is not one job. It is a collection of distinct specialisms, each with its own talent market.

Function	What they deliver	Where they sit in development
Process Development	Design and optimisation of drug substance and drug product manufacturing processes, including scale-up and technology transfer	Preclinical through to commercial launch
Analytical Development	Development and validation of methods to characterise the drug and confirm batch consistency	Every stage, from IND-enabling studies to post-approval
Formulation Development	Translation of drug substance into a stable, scalable and market-ready drug product	Early development through to commercial manufacture
Regulatory CMC	Submission strategy, technical dossier authoring and post-approval change control	IND through to lifecycle management
Manufacturing Science and Technology	Technology transfer, process validation and continuous improvement between development and commercial manufacturing	Late-stage development and commercial operations
GMP Quality and Compliance	Maintaining manufacturing standards, managing deviations and ensuring inspection readiness	Commercial manufacturing and post-approval

The talent shortage is not evenly distributed. Process development, regulatory CMC and MSAT consistently present the greatest hiring challenges, particularly at senior level and across biologics and advanced therapy programmes. These are profiles that require years of highly specific experience and are rarely found through conventional hiring channels.

For organisations building specialist technical teams, EPM Scientific supports hiring across quality and regulatory, manufacturing, pharmaceutical and biotechnology functions. Speak to a specialist about your CMC hiring needs.

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The CMC talent market is under sustained pressure

The data makes the scale of the problem clear.

Together, this reflects a tightening talent market where demand for experienced CMC professionals continues to outpace accessible supply.

Experienced CMC professionals are not sitting in a talent pool waiting to be found. They are employed, well-compensated and deeply embedded in programmes that depend on them. The organizations that secure the best people are not always the ones with the biggest budgets. They are the ones that engage early, understand the market and have access to professionals who will never appear on a job board.

In CMC, by the time a need becomes urgent, the best candidates are already committed elsewhere.

 

What the strongest CMC teams have in common

Having placed CMC professionals across pharmaceutical, biotechnology and CDMO organizations for over a decade, certain patterns hold consistently.

The organizations with the strongest CMC teams invest early. CMC capability built at the preclinical stage pays dividends at every subsequent regulatory checkpoint. Organizations that wait until they need a hire urgently consistently pay more and wait longer.

They plan for their modality. The CMC workforce requirements for a small molecule program are fundamentally different from those for a biologics or advanced therapy programme. Generic workforce planning does not work in a function this specialized.

They access the passive market. Most experienced CMC professionals are not actively looking. The organizations that secure the best people are those that can reach professionals who are not visible through conventional channels.

They build flexibility into their hiring strategy. Contract and interim CMC specialists play a critical role across regulatory submissions, technology transfers, process validation campaigns and inspection preparation. Permanent capability combined with targeted contract support gives organizations the agility to respond to program demands without overextending headcount.

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Finding the right CMC expertise at the right stage

CMC capability is not something most organizations discover they lack at the preclinical stage. They discover it at Phase III, during a pre-approval inspection, or when a complete response letter arrives after years of development investment. By that point, closing the gap costs significantly more in time, budget and regulatory goodwill than building it earlier would have.

The organizations that reach approval without CMC-related delays treated CMC as a strategic function from the start, not a problem to solve when it became urgent. In a talent market this tight, that distinction rarely comes without a cost.

EPM Scientific has placed CMC professionals across pharmaceutical, biotechnology and CDMO organisations for over a decade, from IND-enabling process development through to post-approval regulatory management. Whether you need a single critical hire or are building out a full CMC function, our team is ready to help.

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