In the acronym CMC (Chemistry, Manufacturing, and Controls), each element represents a critical pillar supporting pharmaceutical development. If chemistry is the molecule’s origin story, then manufacturing is the bridge between scientific innovation and real-world application. It’s where an idea becomes a product, where theory meets reproducibility, and where a single successful synthesis must evolve into a global-scale operation.

Too often, manufacturing is treated as a downstream task, something to be sorted once the drug product is developed. In reality, early, strategic attention to manufacturing can make or break a drug candidate’s path to patients.

What manufacturing really means in CMC

Manufacturing in the CMC context refers to the entire process of scaling, reproducing, and standardizing the production of a drug, starting with the API and ending with the final drug product. It spans chemical synthesis or bioproduction, formulation, process optimization, packaging, and integration with quality systems.

Where chemistry defines “what” the drug is, manufacturing defines “how” it gets made: reliably, safely, and at scale.

Key challenges and pillars of CMC manufacturing

Scale-up: From flask to factory

One of the biggest shifts in CMC occurs when a lab process needs to be expanded. Processes that work at a 1-liter scale can behave radically differently at 1,000 liters. Engineers and chemists must navigate:

• Heat transfer and mixing limitations
• Solvent and waste management
• Safety and containment protocols

This scale-up process requires engineering foresight, not just chemical knowledge. It’s a multidisciplinary effort that balances yield, purity, cost, and safety, all under regulatory scrutiny.

Process robustness and reproducibility

Manufacturing is about repetition without deviation. Every batch must meet exacting standards. To achieve this, companies develop and validate:

• Critical Process Parameters (CPPs)
• In-Process Controls (IPCs)
• Standard Operating Procedures (SOPs)

Without tight control of variability, especially in biologics, manufacturers risk batch failures, product recalls, or regulatory penalties.

Formulation and final dosage form

The active ingredient is only part of the medicine. Manufacturing must also address:

• Excipients selection
• Drug delivery format
• Stability

These considerations aren’t just technical, they’re deeply connected to patient experience and adherence.

Facility and supply chain readiness

Manufacturing also involves practical, logistical, and geopolitical factors:

• Are facilities GMP-compliant and inspected?
• Are raw materials available from reliable, audited suppliers?
• Can the manufacturing strategy scale to meet global demand?

This is why companies often invest in tech transfer strategies, moving manufacturing knowledge and processes between sites or external CMOs (contract manufacturing organizations).

Biologics: A whole new manufacturing frontier

Biological drugs, including monoclonal antibodies, mRNA therapies, and cell and gene therapies, introduce even more complexity. Their manufacturing often involves:

• Living cells as factories
• Complex purification processes
• Rigorous cold chain and contamination control

Unlike chemical synthesis, biologics can vary subtly between batches due to the inherent variability of biological systems. Here, process control becomes process science, and robust analytics are essential.

Regulatory expectations: Manufacturing under the microscope

Regulatory bodies such as the FDA, EMA, and WHO expect clear documentation demonstrating that a manufacturer can produce consistent, high-quality product batches over time. Requirements include:

• Detailed process descriptions and flow diagrams
• Batch records and deviation reports
• Validation of equipment, cleaning, and personnel training

Manufacturing documentation is also central to regulatory submissions like the IMPD (Investigational Medicinal Product Dossier) for quality, the IND (Investigational New Drug), the MAA (Market Authorisation Application), and the NDA (New Drug Application).

Manufacturing is the beating heart of CMC

Without robust, scalable, and compliant manufacturing, no drug product, no matter how effective, can reach a patient’s hand. It’s not glamorous, but it is essential. And it requires a fusion of science, engineering, logistics, and regulatory strategy.

So the next time we talk about “CMC,” let’s remember that manufacturing is not just a step, it’s a continuous commitment to quality, reproducibility, and impact at scale. Coming up is the last “C” in CMC which stands for controls — stay tuned.

Interested in learning more?

Read Bengt’s series on CMC, where he discusses each of Chemistry, Manufacturing, and Controls:

CMC in Drug Development: The Bridge from Lab to Market

The “C” in CMC: Why Chemistry Is the Cornerstone of Drug Development

Share Via