How Does WuXi AppTec Accelerate Late-Stage Development and Commercial Readiness for Innovative Oligonucleotide Medicines?

WuXi TIDES, an integral part of WuXi AppTec that provides solutions for oligonucleotides, peptides and related synthetic conjugates, accelerated late-stage development and commercial readiness of an innovative oligonucleotide medicine through process robustness, Quality by Design (QbD), and cost efficiency. WuXi AppTec ensured a seamless handoff from drug substance to drug product, while parallel execution of workflows across active pharmaceutical ingredient (API), analytical, production, and drug product teams reduced the overall timeline. 

Nucleic acid therapeutics have made significant strides over the past decade. New modalities such as antisense oligonucleotides (ASO) are expanding the boundaries of traditional therapies, offering new treatment options for rare diseases, neurological disorders, metabolic disorders, and other conditions. However, these molecules still face a series of development and manufacturing challenges.

Scale-up and validation hurdles: A race to get a biotech’s ASO therapeutic to market

Several years ago, a biotech company was preparing to advance a promising ASO candidate into late-stage development. This program addressed a condition affecting a broad patient population that had few effective treatment options, making it essential to achieve rapid development and dependable availability to meet urgent patient needs.

At this stage, however, production scale-up and process validation faced significant hurdles. The molecule’s complex structure, combined with stringent impurity control requirements, resulted in low yields under the initial process. This led to constraints in clinical supply and manufacturing efficiency, creating uncertainty for late-stage progress. Compounding the issue, the previous vendor was unable to support a smooth scale-up from development to commercial manufacturing. As the project progressed into later stages, the risk of availability disruption increased, potentially delaying the project timeline.

To keep the project on track, the biotech company needed to find a new partner capable of rapid scale-up, process validation, CMC dossier preparation and pre-approval inspection (PAI) readiness within 3 years, while also establishing a cost-effective process early on to support future multiton-scale demand.

Ultimately, they turned to WuXi TIDES.

Immediately following project handover, WuXi TIDES quickly assembled a project team that covered the entire project lifecycle to address both API and drug product process development and manufacturing.

To overcome the limitations of the initial API process, the WuXi TIDES drug substance team utilized its established oligonucleotide technical platform and process development expertise to systematically optimize the process. This approach increased crude purity from less than 70% to 88%. The higher crude purity also simplified the purification process from two steps to one, shortening the process time by 25% and improving manufacturing efficiency. In addition, the optimized process improved overall cost-effectiveness without compromising product quality or yield.

Owing to these advancements and a robust scale-up strategy, the optimized API process performed reliably, enabling the team to deliver multiple process performance qualification (PPQ) batches totaling over 25 kg of ASO in 4.5 months with consistent quality.

The API process demonstrated robustness, high efficiency, and cost‑effectiveness, laying a solid foundation for accelerated late-stage development and future commercial manufacturing. 

On the drug product side, the team focused on minimizing high-value API loss and maximizing overall yield during transfer and filling.

They achieved a 16% reduction in filling waste by implementing sterile single-use distribution systems and designing batch-tailored single-use assemblies. As a result, the final drug product yield exceeded 95%.

The team also efficiently delivered PPQ batches through effective preparation and manufacturing, demonstrating reliable supply and scale-up capabilities in 6.5 months, compared to the industry average of 10–12 months.

Integrated Platform Accelerates Late-Stage Development Timelines and Commercial Readiness

Project timelines were accelerated by both WuXi TIDES’ problem-solving expertise and the synergistic advantages of WuXi AppTec’s integrated CRDMO platform. Under a unified quality system, the platform enables seamless drug substance to drug product handover and parallel execution of activities such as process development, analytical development, and manufacturing.

In this model, each team has a comprehensive view of the timeline, enabling parallel execution without idle waiting or coordination gaps. For instance, while the drug substance team was producing late-stage batches, the drug product team advanced formulation optimization and process development. By the time PPQ batches of drug substance became available, the drug product team had already prepared for PPQ readiness and manufacturing. This collaboration enables the teams to tackle process and capacity constraints, accelerating project timelines and meeting client expectations. 

Built on an integrated platform with consistent processes, analytical methods, and quality systems, this approach increases success rates, minimizes deviations and repetitive re-validation during method transfers, and strengthens data integrity—supporting CMC consistency and regulatory acceptance. The close proximity of drug substance and drug product sites, together with a unified quality system, provides a strong foundation for high-quality, rapid project delivery.

Ultimately, the program advanced from Phase II to PPQ completion in 2.5 years, enabling an accelerated path to NDA submission and laying a strong foundation for future commercial manufacturing. 

Establishing Robust, Commercially Scalable Processes for API and Drug Product

Today, WuXi TIDES offers comprehensive support for oligonucleotide drugs, from discovery to development and commercial manufacturing. In the realm of oligonucleotides, WuXi TIDES has been enhancing its capabilities through innovations such as solid-phase and liquid-phase synthesis, biocatalytic fragment ligation, and other techniques that foster the efficient construction of complex sequences. Downstream, innovative technologies such as thin-film evaporation and continuous flow chromatography are utilized to streamline workflows and simplify processing steps. 

WuXi TIDES leverages a Quality by Design (QbD) approach and upholds high quality standards at each stage of development, as it continues to leverage its integrated, end-to-end CRDMO platform and extensive experience to enable clients to accelerate the research, development, and manufacturing of new drugs to bring benefit to patients globally.

Key Takeaways:

1. WuXi TIDES, a CRDMO platform that is an integral part of WuXi AppTec, is capable of rapid scale-up, process validation, and pre-approval inspection (PAI) readiness for an ASO drug, while also establishing a cost-effective process early to support future multi-ton demand.
2. WuXi TIDES has established capabilities spanning API and drug product, supporting oligonucleotide drugs from discovery to commercial manufacturing.
3. In the oligonucleotide field, WuXi TIDES has been advancing its capabilities in recent years through innovations such as solid-phase and liquid-phase synthesis, biocatalytic fragment ligation, and techniques that improve the efficiency of constructing complex sequences. 
4. Under a unified quality system, WuXi AppTec’s integrated CRDMO platform enables seamless drug substance to drug product handover and parallel execution of process development, analytical development and manufacturing.