CMC Strategy: The Key to Success for Biologics

In biotech, great science alone isn’t enough. The journey from discovery to commercialization of a novel drug requires more than just breakthrough research—it demands a strong foundation in Chemistry, Manufacturing, and Controls (CMC). While groundbreaking discoveries in drug development can generate initial excitement and funding, they can often fail to reach patients in the end due to overlooked challenges in manufacturing and regulatory compliance. This is the productization process: developing something that might start as just a research discovery into a drug substance and then a drug product.

However, many biotech founders don’t think about CMC until it causes problems which could have been avoided with a proactive approach. Developing a promising therapy is only part of the equation; ensuring that it can be consistently produced at scale with a process that meets strict regulatory requirements is equally essential. Scientists and business professionals may not be aware of all the considerations that must go into planning for future manufacturing scale-up of a drug or vaccine. A lack of phase-appropriate CMC strategy is one of the biggest roadblocks to regulatory approval, scale-up, and commercial success, leading to more failures than unfavourable trial outcomes. Companies that neglect CMC early in development often face costly setbacks, including clinical holds, delayed approvals, and manufacturing failures that can threaten their entire pipeline.

The Role of CMC in Drug Development

CMC encompasses all the activities necessary to ensure that a drug product is consistently produced with the required quality, safety, and efficacy. From early-stage formulation to GMP manufacturing and regulatory submissions, CMC planning is integral to avoiding costly delays and development failures. In drug development, additional testing or data requests from regulators should be expected and planned for with contingencies rather than leading to surprises.

CMC Strategy as a Driver of Success Across Development Phases

A well-defined phase-appropriate CMC strategy is a central driver of success across every stage of biologics development, influencing not only regulatory outcomes but also speed, cost, scalability, and ultimately commercial viability.

Early Development (Discovery to Preclinical): Building the Right Foundation

At the earliest stages, CMC strategy shapes the trajectory of a biologic long before it enters the clinic. Thoughtful selection of expression systems, vector design, and initial process development can significantly impact yield, product quality, and scalability. Early characterization of critical quality attributes (CQAs) and development of fit-for-purpose analytical methods reduce downstream risk by ensuring the molecule is well understood from the outset.

A strong early CMC approach also avoids common pitfalls such as choosing platforms that are difficult to scale or relying on unstable cell lines. By prioritizing developability early, companies can prevent costly rework later and position their asset for smoother progression into clinical manufacturing.

Projects at this stage: This is the ideal stage to select optimal technologies for process efficiency and bringing down CoGs. For example, we've worked with companies to evaluate potential microbial expression systems, single-step membrane chromatography, gentler pumps, and even growth factors to optimize process yields and bring costs down to cents per dose before the process is locked in. When companies are preparing to initiate clinical trials, Omnium Global has also worked with them to redesign processes for scalability up to >10,000L.

Clinical Development (Phase I–III): Enabling Speed, Flexibility, and Compliance

As a biologic advances into the clinic, CMC becomes a key enabler of both speed and adaptability. In early clinical phases, the focus is on establishing robust, reproducible processes that can generate material quickly while meeting regulatory expectations for safety and quality. Platform technologies and modular process designs are particularly valuable here, allowing for accelerated timelines and reduced development burden.

Moving into later-stage trials, the emphasis shifts toward process consistency, comparability, and scalability. Changes made during this phase—such as process optimization or site transfers—must be carefully managed to demonstrate comparability and avoid regulatory delays. A proactive CMC strategy ensures that these transitions are anticipated and supported by appropriate analytical and regulatory frameworks.

Importantly, CMC also underpins regulatory interactions throughout clinical development. Well-documented processes, validated analytical methods, and a clear control strategy build confidence with regulators and reduce the likelihood of clinical holds or approval delays.

Projects at this stage: At this stage CDMO selection and rapid tech transfer to GMP manufacturing is key. We've supported clients with shortlisted CDMO due diligence and contract negotiations to sign partners and kick-off tech transfer within as little as 2 months from publishing of their RFP. At this stage CMC project management is also key, ensuring TPP development, adjuvant formulation, USP and DSP macro level optimization, equipment and consumables are purchased, manufacturing QC assays, and records management all run smoothly and on schedule.

Commercialization: Securing Supply and Competitive Advantage

At the commercial stage, CMC becomes a strategic lever for long-term success. Scalable, cost-efficient manufacturing processes directly impact margins, while a robust control strategy ensures consistent product quality and supply reliability. This is particularly critical for biologics, where manufacturing complexity can pose significant risks to supply continuity.

A mature CMC strategy also enables lifecycle management opportunities, such as process improvements, formulation enhancements, or new presentations. These can extend product value, improve patient access, and strengthen market positioning.

Additionally, regulatory expectations at this stage are highest, requiring fully validated processes, comprehensive stability data, and ongoing process verification. Companies that have invested in a strong CMC foundation earlier in development are far better positioned to meet these demands without disruption.

Projects at this stage: At this stage there are still opportunities for process optimization and intensification. For example, we've worked with commercial vaccine facilities to modernize their cell culture to perfusion and introduce clarification technologies to increase annual facility throughput. We've also designed processes for producing commercial quantities of mAbs at bench scale through perfusion and continuous chromatography. For companies exploring global expansion of their markets, micro-facilities are also an area they can explore. We've worked with companies to design low-cost fully autonomous microfacilities with capacities of millions of doses/yr with footprints of <1000m2.

Why CMC Matters:

The main reasons to consider CMC early are:

1. Regulatory Agency Requirements: Without a well-defined CMC strategy, regulatory agencies may raise concerns that lead to clinical holds or rejection of applications. If there is no regulatory precedent, this can also lead to approval delays. CMC dossiers are a basic requirement for inclusion in all regulatory authority submissions. It is also key to establish a robust QMS that will support a phase-appropriate approach.

2. Manufacturing Scalability: A process that works in the lab doesn’t always translate to large-scale production. Addressing all potential scale-up challenges early (including equipment selection, process robustness, and vendor capabilities) can prevent significant delays. Equally important is ensuring that early vendors have the ability to provide GMP qualification when needed in your development.

3. Quality and Consistency: Robust analytical validation and process controls are critical to ensuring batch-to-batch consistency, a key requirement for approval and commercialization. Choosing the right CDMO to implement your CMC plan is also an important strategic decision that ensures you won’t have to rework processes in later phases.

4. Cost and Timeline Efficiency: Early CMC planning helps avoid costly rework, batch failures, or redevelopment when moving between phases or vendors. A phase-appropriate approach also means you are only spending resources on what is needed at your current stage of development. Poorly defined CMC can lead to extended timelines, wasted materials, and spending your budget on the wrong things - a major risk for small biotech companies with limited runway.

The Cost of CMC Missteps

A misstep in process development, analytical validation, or technology transfer can set a drug development program back by years. Issues such as uncontrolled impurities, inconsistent manufacturing processes, or inadequate stability data can lead to regulatory rejections, costly rework, and even failed clinical programs. Waiting until a regulatory agency review to find out what you missed may mean it is too late, or the investment required to resolve issues will be too high. Not adopting a risk-based approach dependent on phase can lead to budget issues that sacrifice the late phase needs of the program. Investing in CMC expertise early and strategically helps mitigate these risks, ensuring that promising therapies reach patients faster and more efficiently, while minimizing the development costs and level of stress on you the founders.

De-Risking Development with CMC Expertise

Strategic CMC planning is not just a regulatory necessity, it’s a competitive advantage. Companies that integrate CMC considerations early in development are better positioned to:

• Avoid clinical and regulatory setbacks

• Optimize manufacturing processes for scalability

• Reduce development costs and timelines

• Improve the likelihood of commercial success

  
  

Whether you’re an early-stage biotech navigating preclinical development or preparing for late-stage manufacturing and commercialization, the right CMC expertise can make the difference between success and failure. Beyond just a risk mitigation strategy, CMC is also a value driver for biotechs. It's critical for every company to have a CMC team on board at the start of their journey. Ultimately, CMC is not a support function—it is a core pillar of product strategy. Companies that treat it as such move faster, de-risk earlier, and are far more likely to translate innovation into real-world impact.

At Omnium Global, we help biotech companies leverage best practices to move forward with confidence and accelerate their path to market. Our scientific team is made up of experts with over 25 years of experience each in working with complex biologics, including vaccines, mAbs, recombinant proteins, viral vectors, oncolytic viruses, VLPs, cell therapies, and more. We can also guide you in process development, optimization, and intensification.

If you’re at the stage where you’re starting to think about your product’s CMC strategy, let’s connect! Even if you don’t know where to start, be assured that we do.