The sterile outsourcing industry is at a crossroads. The rapid expansion of biologics, cell and gene therapies, and innovative high value, low volume drugs has fundamentally shifted the demand for parenteral drug development and manufacturing services. Small and medium-sized biotech companies, which drive much of this innovation, are facing a harsh reality—outsourced sterile manufacturing capacity, expertise, and flexibility is stretched thin. 

With timelines extending up to 18 months, getting into early-phase clinical trials has never been more challenging. Contract development and manufacturing organizations (CDMOs) are in a unique position to step up and reshape this ecosystem. The industry must rethink facility design, embrace niche expertise, and invest in skilled talent to ensure that processes evolve to meet the growing demand. The question is: are CDMOs ready for this transformation?

The shift toward small-batch biologics

The rise of precision medicine is driving demand for small-batch biologics. Unlike traditional large-volume pharmaceuticals, these therapies require highly flexible, small-scale sterile fill-finish capabilities. Personalized medicines and high-concentration biologics have unique requirements that challenge the traditional high throughput development and manufacturing model typically seen across the industry.

Companies are seeking confidence from CDMOs where pathways to commercialization are not only visualized but also acted upon. As demand for small-volume commercial batches rise, smaller CDMOs can become the preferred choice. However, historical M&A activity has led to their consolidation, reducing the number of available options. These smaller CDMOs offer significant advantages, including greater scheduling flexibility and adaptable process trains, which are often harder to implement in larger organizations. Maintaining access to these nimble partners is critical for biotechs looking for efficient, customized sterile manufacturing solutions.

Those that once prioritized large-batch production must now pivot toward agile, multi-product facilities. This shift brings operational complexities, including increased changeovers, more rigorous contamination controls, and the need for highly specialized fill-finish expertise. The development of innovative powder based sterile products requiring modifications to traditional fill-finish production lines adds an additional level of complexity. The industry is struggling to keep pace, and innovators are withstanding the worst of the bottlenecks.

The capacity crunch

As a result, manufacturing capacity for sterile injectables is at a premium. Facilities capable of manufacturing small batch sizes, handling biologics and using novel processing technologies are oversubscribed, leaving emerging biotechs scrambling for manufacturing slots and access to formulation development. Many are facing an 18-month wait to go from initial formulation development to clinical trial supply.

These delays are more than just an inconvenience. Speed is vital for those organizations where future funding milestones are reliant upon getting into the clinic and initial trial results provide a green light for additional funding rounds. Being able to quickly determine whether a drug is going to be viable for future development is extremely time sensitive. The industry cannot afford these bottlenecks, and CDMOs must rethink how they allocate capacity to ensure early-phase innovators get the access they need.

The challenge of availability and timelines

Beyond sheer capacity constraints, fill-finish itself presents unique challenges. CDMOs tend to prioritize large-scale commercial batches over small, complex fills. This leads to limited availability of small-scale sterile lines, creating longer timelines due to complex tech transfers, and difficulties in handling powders and other complex formulations. 

Due to specific patient groups, there is now more demand for low volume commercial products. It can be a struggle for larger manufacturers to put small batches onto a large commercial line due to turnaround times. For small and medium-sized biotech firms, these challenges can be make-or-break. The need for CDMOs that specialize in small-batch, flexible fill-finish services has never been greater.

The requirement for specialist expertise

This specialism can take many forms due to some parenteral products that are not typically stable in liquid or frozen form, or the required doses are not achievable due to the inherent solubility of the drug substance. For example, traditional methods such as freeze-drying cannot be applied for some high concentration biologics; therefore, there are a growing number of sterile powder products requiring aseptic spray drying, highlighting the requirement for CDMO investment into new capabilities and technologies.

Powders typically create challenges within sterile environments requiring specialist expertise to work with them. This creates a gap for current formulation technologies to meet the requirements where conventional processing techniques can’t achieve the drug product that is needed. Spray drying lends itself to this and opens opportunities with the sterile landscape.

Another consideration is the analytical challenges associated with developing complex, next generation biologics; the need for a broad range of analytical expertise and instrumentation relating to both powder and liquid formulation analysis is key to the successful development of these new products. 

Facility design: the key to speeding up clinical trials

Facility design is often an overlooked factor in sterile outsourcing delays. Traditional sterile manufacturing sites are built for high throughput efficiency, not for the agile demands of small-batch biologics. Working with small biotechs requires a different approach.

With the introduction of the revised Annex-1 guidelines in August 2023, the industry is moving towards closed systems and isolator technology to enhance sterility assurance while enabling rapid processing. Traditional open cleanroom setups require extensive environmental monitoring and gowning procedures that slow down production. Isolators, in contrast, minimize human intervention, reducing contamination risks and improving batch release timelines.

Whether it is a new build or redesign of an existing facility, adopting flexible cleanroom designs becomes a facilitator for quick changeovers, rapid scaling of production volumes, multiproduct capabilities without lengthy revalidation, and reduced downtime between batches.

Mitigating technical transfer risks

To support speed into the clinic and a pathway to commercialization, buyers are looking for CDMOs that are familiar with formulation development, sterile manufacturing and scale up, but specifically those that offer this on one site, reducing the requirement for additional cost, time delays and risks that typically come when carrying out technical transfer between sites or other CDMOs.

It can take 6 months to transfer a process from one CDMO to another adding unnecessary complications and risk. Those CDMOs that have powder and sterile expertise within one site have an advantage over others. During tech transfer, to almost start from scratch with new project teams, new agreements and processes, these tend to be timescales that put added pressure on progressing the product development quickly.

Where teams work together across one site, it becomes easier to visualize coming out of the clinic and the onward development journey of sterile drugs, looking at the scale up and next phase of the clinical trial manufacturing as one.

The role of people in sterile manufacturing

While facility designs are becoming more advanced and complex, people remain at the core of sterile outsourcing. The industry is facing a talent shortage, particularly in aseptic product development and manufacturing of more complex sterile products, making it essential for CDMOs to invest in highly skilled and experienced staff. 

Honest communication between departments is also crucial, enabling cross-functional problem-solving and greater agility in responding to manufacturing challenges. Attracting and retaining skilled talent, while ensuring seamless collaboration, will be just as critical as investing in new facilities.

From service providers to strategic partners

Historically, CDMOs have been seen as manufacturing service providers. Today, they must evolve into strategic partners. Biotech innovators do not just need capacity, they need CDMOs with the agility to support rapid development, streamlined regulatory pathways, and specialist expertise in areas such as aseptic processing across both conventional technologies and emerging ones like spray-dried powders.

It’s clear that the sterile outsourcing landscape is changing quickly. As demand for small-batch products rises and capacity remains constrained, CDMOs must step up to the challenge. They must rethink their business models. Those that offer agile capacity, specialized fill-finish capabilities, and cutting-edge facility design will become the go-to partners for biotech innovators and become their CDMO partner of choice.

As CDMOs, we need to support biotech and emerging pharma who are innovative and creative. As they continue to develop novel therapeutics, we have a responsibility to support them. They are looking for multi-talented teams, creative solutions to product development, scale up and strategic partners who have flexible and reactive project teams. 

The question is no longer whether CDMOs can keep up—it is whether they recognize that this is what biotechs need. The companies that embrace this will define the future of sterile outsourcing.

Nikki Whitfield is CEO of Upperton Pharma Solutions, a Nottingham-based CDMO specializing in formulation development, clinical trial manufacturing and manufacturing services for a wide range of dosage forms, including oral solids, liquids, semi-solids, and inhalation products. She has 30 years’ technical and operational leadership experience gained in both pharmaceutical companies and CDMOs. Working across a range of dosage forms with both small molecules and biologics, Nikki has successfully led drug development programs from early phase pharmaceutical development through to late stage and pre-launch stages covering all aspects of the programs including technical design, manufacturing, process scale-up, regulatory submission and clinical trial supply.