Three Months to Recover Lost Time: How WuXi AppTec Helped a Drug Program Get Back on Track

New drug development involves long timelines and multiple steps. Each step is critical and full of uncertainties, and challenges sometimes come precisely from the steps that are easily overlooked.

One morning a few years back, an unscheduled meeting was taking place in a conference room at WuXi STA, a subsidiary of WuXi AppTec.

A client had just called: a new small-molecule drug they had submitted for market approval was under review by the EMA and had received a query concerning the regulatory starting material (RSM).

The regulatory starting material defines the starting point of the process described in an active pharmaceutical ingredient (API) regulatory filing, and also the starting point for GMP implementation and change management. An RSM can be a raw material or an intermediate that is a significant structural component of the final API. Impurities contained in the RSM, as well as process-related impurities generated in subsequent reactions, may carry through to the final API. Therefore, RSM selection and quality control are important parts of overall API development and manufacturing.

When developing a CMC strategy, people often focus their attention on the downstream activities, such as late-stage API processing and drug product launch, while overlooking upstream elements such as the RSM. If a regulatory agency challenges the designation of the RSM, all downstream development work may need to be re-evaluated or repeated. And if a project involves filing in multiple countries with differing regulatory requirements, the risk of the RSM being challenged becomes even more acute.

The client on the phone was facing exactly this dilemma. To make matters more difficult, the project had been acquired by the client and lacked the original technical package, and the original supplier was no longer able to provide additional support.

Planning Ahead: Risk Anticipated Six Months Early

In fact, this seemingly sudden crisis had already been anticipated by the WuXi STA team six months earlier.

In the previous autumn, the WuXi STA team had just taken over late-stage process development and filing work for this project. Drawing on their extensive filing experience and deep understanding of global regulations, the team quickly identified a potential RSM risk. They promptly notified the client of the risk and proactively proposed conducting small-scale validation studies as a contingency plan. The client accepted this proposal.

Image Source：123RF

When the risk eventually materialized, this preparatory work provided an important foundation for recovering lost time.

However, the clock was ticking. Under standard industry practice, similar work would typically take seven to nine months. Even with preliminary studies already in place, the work would still take around six to seven months.

But the deadline given by the client at that time was only four months.

The Integrated Platform: Helping the Customer Win Back Time

At the critical moment, WuXi AppTec’s integrated platform played a critical role.

In a traditional project execution model, the workflow is linear. Each step must wait for the previous one to finish, resulting in a long overall timeline.

But on WuXi AppTec’s integrated platform, the workflow is restructured into a highly parallel model — process development, analytical support, quality systems, manufacturing execution, testing and release. Every module operates simultaneously and seamlessly, significantly compressing the project timeline.

Faced with an incomplete original technical package, the WuXi STA team worked to fill in the experimental protocols while simultaneously establishing analytical methods. At the same time, they seamlessly coordinated cross-functional teams and manufacturing facilities, completing hundreds of quality studies and process validations, and generating all the data needed to update the client’s regulatory filing.

All of this was made possible by WuXi AppTec’s integrated, end-to-end CRDMO enabling platform. On this platform, multiple technology platforms provide solid support for integrated collaboration. For example, the process engineering team used design of experiments (DoE) and analytical modeling to conduct engineering risk assessments and simulations of the scale-up process. By verifying manufacturing robustness under extreme conditions, they ensured a smooth scale-up from gram-level in the lab to hundred-kilogram manufacturing scale. The high-throughput process development platform accommodated large-scale reaction exploration: several parallel synthesizers in the lab could run more than ten reactions simultaneously, greatly accelerating process development. The analytical teams developed multiple challenging analytical methods in parallel, ensuring that testing and validation progressed simultaneously.

If the company’s comprehensive chemistry technology platforms represent its “hard power,” then meticulous project management and team execution capabilities are its indispensable “soft power.” To accomplish this seemingly impossible task while advancing the project, the team broke away from daily and weekly planning cycles, refining project execution and progress tracking to hourly precision. Each process step, each test, and each release had a precise timeline and a clearly designated responsible person. Every person in charge knew that their time window was only a few hours. 

Image Source：123RF

In the end, the team took only three months — a full month ahead of the timeline the client had expected.

While exceeding the client’s expectations for speed, the quality remained robust: throughout the entire validation process, all batches were delivered with zero deviations, earning high praise from the client.

The new drug subsequently passed regulatory review and was successfully launched, continuing to serve the clinical needs of countless patients.

The client’s satisfaction translated into lasting trust: commercial manufacturing of the project has stayed with WuXi STA, and the client has become a long-term partner of the company, entrusting it with additional follow-up projects.

This resolution of the client’s RSM challenge exceeded expectations, yet at first glance it appeared to be a difficult problem solved under pressure. In reality, it was a systematic demonstration of the capabilities of WuXi AppTec’s integrated CRDMO platform. With regulators imposing stricter expectations for RSMs, WuXi AppTec has strengthened its integrated CRDMO platform to better mitigate project risk. The company implements stage appropriate RSM risk mitigation and filing strategy based development plans. It can also back integrate key/raw starting materials into its own facilities, providing end to end process development through manufacturing to enhance quality and flexibility. When regulators require more information on RSM definitions, the team can respond rapidly — for example, completing Quality by Design (QbD) and Process Performance Qualification (PPQ) within 12 weeks to redefine the RSM and address regulatory concerns.

Forward-looking risk assessment and preparatory studies, highly parallel and seamlessly connected process execution, and meticulous project management and team execution —were the inevitable result of the platform’s long-term accumulation and continuous optimization, and the very essence of the “integrated” model.

Compressing the timeline does far more than shorten the delivery cycle. It represents a solid fulfillment of WuXi AppTec’s commitment to its customers. When a new drug passes regulatory approval and reaches patients, all the efforts converge into a single, simple answer: Every drug can be made, and every disease can be treated.