From Phase 3 to Commercialization: What Sponsors Need from a Sterile Injectable CDMO

Sterile injectable programs can get much harder to manage as they move closer to Phase 3 and commercial production. Sponsors are often dealing with tighter capacity, longer lead times, more complex regulatory requirements, and the need to make sure their manufacturing partner has the right infrastructure and technical experience in place.

In this Pharma Matters Q&A, Ryan Downey, Vice President of Technical Operations at August Bioservices, discusses what sponsors should look for in a late-stage sterile injectable CDMO. He examines the impact of Annex 1, growing demand from GLP-1 and other high-volume therapies, the importance of integrated technical capabilities, and why selecting the right manufacturing partner early can help reduce risk as a program approaches commercial launch.

Contract Pharma: How would you describe the current sterile injectable CDMO landscape, especially for companies moving into Phase 3 or commercial manufacturing?

Ryan Downey: Today’s CDMO landscape is evolving rapidly as the industry responds to growing demand for sterile injectable manufacturing, specialized expertise, and facilities designed to meet Annex 1 requirements. At the same time, demand to re-shore pharmaceutical manufacturing to the U.S. are increasing for the limited CDMO capacity currently available domestically.

As a result, CDMOs that invested in Annex 1-compliant equipment and facility infrastructure two to three years ago are now in the strongest position to support late-stage clinical and commercial programs. These organizations are better equipped to help sponsors of innovative therapies accelerate timelines while meeting the quality, regulatory, and manufacturing expectations required for commercialization.

CP: Commercial sterile fill-finish capacity remains under pressure. Where are sponsors feeling that strain the most today?

Ryan: The pressure sponsors face today is driven by three interconnected challenges.

First, access to fill-finish capacity that can support both current development needs and long-term commercial growth remains limited. As CDMOs work to expand capacity, many are constrained by extended lead times for critical equipment from leading OEM suppliers, making it difficult to bring new manufacturing lines online quickly.

Second, access to experienced subject matter experts (SMEs) has become just as important as access to manufacturing capacity. Successfully implementing advanced fill-finish technologies and achieving efficient, compliant commercial readiness requires deep technical expertise. For sponsors, evaluating a CDMO extends beyond assessing equipment and facilities—it also requires understanding the strength of the organization’s scientific and technical teams. CDMOs with experienced, in-house SMEs are better positioned to collaborate directly with sponsors’ technical leaders, providing the scientific guidance and partnership needed throughout process development, technology transfer, and commercialization.

Third, supply chain constraints continue to challenge the sterile fill-finish market, particularly for primary container-closure components and single-use systems. CDMOs that standardize manufacturing platforms and process designs are better equipped to strengthen supplier relationships, maintain strategic inventory, and secure more reliable sourcing. This operational flexibility enables faster onboarding of new products while reducing supply chain risk during process development and commercial launch.

CP: What makes late-stage sterile injectable programs more challenging than earlier clinical-stage work?

Ryan: Late-stage sterile injectable programs have fundamentally different requirements than early-stage development programs. During the early phases, the primary focus is on understanding and characterizing the drug product. As programs advance toward late-stage clinical development and commercialization, priorities shift to process robustness, scalability, and operational efficiency as process validation and commercial readiness become the central objectives.

One of the most significant challenges at this stage is securing the large quantities of primary container-closure components required for validation and commercial manufacturing campaigns. These materials often have extended lead times, making them a critical determinant of manufacturing timelines. In contrast, early-stage programs typically require smaller quantities that can often be sourced from vendor “small stock” inventories specifically maintained to support clinical development.

Beyond manufacturing, late-stage programs require a broad range of supporting studies to strengthen regulatory submissions and prepare products for commercialization. These often include nitrosamine risk assessments and testing, extractables and leachables studies, in-use compatibility assessments, device functionality testing, shipping and distribution studies, and other regulatory support activities.

For many sponsors, identifying qualified providers for these specialized studies is only part of the challenge. Each service provider must then be managed independently, requiring coordination of study protocols, sample shipments, timelines, data review, and final reporting. This fragmented approach can introduce unnecessary complexity, increase project management burden, and create delays when timelines are most critical.

Sponsors should prioritize CDMO partners that offer most of these regulatory support services within their own organization or across an integrated network of facilities. Centralizing these capabilities enables better coordination, more predictable turnaround times, and faster decision-making throughout development.

Integrated support becomes especially valuable when unexpected testing outcomes occur. Non-conforming results are an inevitable part of pharmaceutical development and require timely scientific investigation to avoid disrupting program timelines. While many third-party laboratories provide high-quality analytical services, investigation timelines often fall outside a sponsor’s control. CDMOs that manage both sterile fill-finish manufacturing and the supporting analytical and regulatory services are better positioned to rapidly investigate, resolve, and disposition non-conforming results, helping sponsors maintain development momentum while reducing execution risk.

CP: Contract Pharma’s survey showed that technical expertise is the top factor sponsors consider when selecting a CDMO. What does technical expertise mean in a late-stage sterile injectable program?

Ryan: As sterile injectable programs transition toward commercialization, sponsors must make critical decisions regarding process controls and monitoring strategies, single-use system selection, equipment reliability, and overall manufacturing robustness. These decisions have a direct impact on process consistency, regulatory readiness, and long-term commercial success.

CDMOs with demonstrated experience supporting both early-stage clinical development and commercial manufacturing are best positioned to guide these decisions. Their technical subject matter experts (SMEs) have experience establishing innovative manufacturing processes during early development, where flexibility and scientific problem-solving are essential, while also optimizing those processes into standardized, repeatable operations that prioritize reliability, scalability, and compliance for commercial production.

Late-stage programs also introduce greater operational complexity. Larger batch sizes, advanced automation platforms, and higher throughput requirements demand close collaboration between Manufacturing Science and Technology (MSAT), Operations, Engineering, Quality, and Automation teams. CDMOs with strong cross-functional technical expertise can work alongside sponsors to maximize the performance of these manufacturing platforms while minimizing operational risk.

Examples include optimizing fill speeds to increase throughput without compromising product quality and reducing false rejects during automated visual inspection to improve yield and manufacturing efficiency. These specialized capabilities not only enhance operational performance but also help sponsors accelerate commercialization, improve process reliability, and reduce the total cost of manufacturing over the lifecycle of the product.

CP: How are more complex injectable formats, including prefilled syringes, autoinjectors, and combination products, changing what sponsors need from CDMO partners?

Ryan: As drug-device combination products become increasingly common, fill-finish CDMOs must possess a deeper understanding of the device-related aspects of the programs they support. Service providers with experience manufacturing more complex delivery systems—such as pre-filled syringes—should also offer advanced expertise in container compatibility and device performance assessments.

Sponsors should seek CDMOs that demonstrate a strong understanding of industry standards such as ISO 13485 and ISO 11040, which provide the framework for the design, characterization, and performance evaluation of pre-filled syringe systems. These considerations can significantly influence development timelines, as device qualification, packaging design, and compatibility studies are often critical path activities that must be completed to support regulatory submissions.

CDMOs that offer these capabilities in-house are better positioned to partner with sponsors throughout the product lifecycle, from study design and execution to data interpretation and final reporting. An integrated approach improves coordination, reduces reliance on multiple external vendors, and provides greater confidence in project timelines.

Equally important is an understanding of how device manufacturing processes influence product performance. For pre-filled syringes, for example, factors such as container dimensions, silicone application, needle configuration, and component interactions can directly affect functionality, product quality, and patient usability. CDMOs with expertise in these areas can help sponsors identify and mitigate potential risks early in development, while those without this knowledge may be limited in their ability to provide effective technical guidance. As combination products continue to evolve, device expertise has become an increasingly important differentiator in selecting the right fill-finish manufacturing partner.

CP: What impact are GLP-1 products and other high-volume therapeutics having on sterile manufacturing capacity across the industry?

Ryan: The rapid growth of GLP-1 therapies and other high-volume injectable products is placing unprecedented demand on sterile fill-finish capacity across the industry. Many of these therapies require commercial-scale manufacturing campaigns that occupy production lines for longer periods of time and consume significantly larger volumes of primary container-closure components, single-use systems, and manufacturing resources than traditional specialty products. As a result, sponsors are facing increased competition for available manufacturing capacity, longer scheduling lead times, and greater pressure on critical supply chain materials.

Beyond capacity constraints, GLP-1 products introduce unique technical considerations that can influence facility selection and manufacturing strategy. As peptide-based formulations, GLP-1 therapies are sensitive to environmental factors such as light, elevated temperatures, and mechanical stress, requiring carefully designed manufacturing processes to maintain product stability.

In some cases, GLP-1 formulations also present material compatibility challenges. Certain formulations may be incompatible with gamma-irradiated materials, limiting the use of single-use technologies that have become common in sterile manufacturing. When this occurs, manufacturers may need to rely on stainless steel process equipment, requiring facilities with the infrastructure, cleaning capabilities, and operational expertise to support these more complex manufacturing platforms.

As demand for GLP-1 products continues to grow, sponsors should evaluate CDMOs not only on available capacity, but also on their flexibility to support both single-use and stainless-steel manufacturing platforms, their ability to scale commercial production, and their experience managing the unique processing requirements associated with high-volume peptide therapeutics.

CP: How are Annex 1 and other evolving regulatory expectations affecting the way sponsors evaluate sterile injectable CDMOs?

Ryan: With the introduction of EU GMP Annex 1, the focus across the sterile injectable industry has shifted toward a contamination control strategy as the foundation for all manufacturing activities. To meet these expectations, CDMOs have been required to assess their facility and equipment designs, process flows, and materials to identify compliance gaps. Addressing these gaps often requires significant investments in both capital and technical expertise, with implementation timelines that can vary considerably depending on the age of the facility and existing infrastructure.

In contrast, organizations that have designed and commissioned new facilities or fill-finish lines within the past five to six years have generally been able to incorporate Annex 1 principles from the outset. As a result, these CDMOs are often better positioned to support sponsors seeking manufacturing partners with modern, inspection-ready operations.

Sponsors are increasingly evaluating Annex 1 readiness as part of the CDMO selection process because organizations with mature compliance programs are typically better prepared for successful regulatory inspections. At the core of Annex 1 is the ability to integrate equipment design, aseptic processing, PUPSIT, personnel and material flows, and contamination control practices into a holistic Contamination Control Strategy (CCS) that evolves as the site matures. Sponsors should look for evidence not only of these foundational elements, but also of a demonstrated commitment to continuously improving the CCS through ongoing risk assessment and operational excellence.

CP: Why is validated infrastructure so important for late-stage and commercial customers?

Ryan: In regulated manufacturing, “validated” carries a precise meaning: equipment, facilities, utilities, and computer systems must have documented evidence that they consistently perform as intended, within specified parameters. It is a formal regulatory requirement under current Good Manufacturing Practice (cGMP).

By Phase 3 and especially at commercial launch, regulatory bodies such as the FDA and EMA expect the manufacturing process to be locked down and demonstrably reproducible. Without validated infrastructure, the regulatory filing cannot proceed, and the entire approval hinges on demonstrating control and consistency.

“By commercialization, success is measured by the ability to reliably reproduce the same process and product quality with every manufacturing run.”

Pre-validated infrastructure represents a meaningful competitive advantage. It allows a late-stage sponsor to transfer their process into an existing facility rather than building out and validating new infrastructure from scratch, shaving months off development timelines.

Late-stage and commercial manufacturing sites are subject to Pre-Approval Inspections (PAI) and routine GMP audits. Commercial-stage computer systems including MES, LIMS, and batch record systems, must meet 21 CFR Part 11 / Annex 11 requirements. Validated infrastructure ensures that the data underpinning batch release is trustworthy and fully traceable as well.

Commercial products go to patients on an ongoing basis and poorly or unvalidated infrastructure creates real risk of batch failure, contamination, or recalls with legal and reputational consequences far beyond a failed clinical batch.

Early-stage programs prioritize speed and flexibility, whereas late-stage and commercial programs demand consistency. By commercialization, success is measured by the ability to reliably reproduce the same process and product quality with every manufacturing run.

CP: For sponsors preparing for commercial launch, how important is it to have U.S.-based sterile injectable manufacturing capacity available now?

Ryan: With the U.S. representing the world’s largest pharmaceutical market, many drug innovators are prioritizing U.S.-based manufacturing as they prepare for commercial launch. Securing sterile injectable capacity early not only supports access to this key market but also provides greater flexibility as programs transition from clinical development to commercial production.

Beyond market access, manufacturing closer to the end market strengthens supply chain resilience. Domestic production can reduce shipping complexity, shorten lead times, and minimize the risks associated with transporting sensitive sterile injectable products internationally. In today’s evolving geopolitical and regulatory environment, many sponsors also view U.S.-based manufacturing as an important strategy for mitigating supply chain disruptions.

Equally important is establishing the right manufacturing partnership early. Working with a CDMO that can support a program from development through commercialization helps streamline technology transfer, reduces scale-up risk, and builds process knowledge over time. For many sponsors, U.S.-based manufacturing is no longer just a logistics decision—it’s a strategic investment in long-term commercial success.

CP: What advice would you give companies that may need sterile fill-finish or commercial manufacturing support in the next 12 to 24 months?

Ryan: Sponsors should focus their CDMO evaluations on organizations that offer a broad, integrated portfolio of services, allowing them to benefit from greater operational efficiency, technical continuity, and in-house expertise throughout the product lifecycle. CDMOs with modern facilities and advanced automation platforms are also more likely to be well positioned for Annex 1 compliance and should be given strong consideration.

Once a potential partner has demonstrated the right facilities, equipment, and technical capabilities, the evaluation should shift to the people behind the operation. It is essential to assess whether the CDMO’s subject matter experts and project teams have the experience, collaborative approach, and technical judgment to complement the sponsor’s organization. The strongest partnerships are built on a shared commitment to solving problems together, creating a level of collaboration where the distinction between sponsor and CDMO becomes secondary to the success of the program.

Learn more at www.augustbio.com