新药研发周期长、环节众多，任何一个环节都至关重要且充满变数，而挑战有时恰恰来自那些容易被忽视的环节。

几年前的一个清晨，药明康德子公司合全药业的一间会议室里，一场临时会议正在进行。

客户刚刚来电：他们一款正在申报上市的小分子新药，受到了欧洲药品管理局（EMA）的质疑，问题出在了监管起始物料（Regulatory Starting Materials，RSM）上。

监管起始物料是原料药注册申报工艺描述的起点，也是药品生产质量管理规范（GMP）实施和变更管理的起点。它可以是该原料药结构中重要组成部分的原材料、中间体或其他原料药，其所含的杂质及后续反应中生成的转化产物，都有可能被带入最终的原料药中。因此，RSM的选择与质量控制，是整个原料药开发的重要组成部分。

在制定CMC方案时，人们的关注点往往集中于药品开发供应链的下游，如原料药的后期工艺直至药品上市环节，而对上游的RSM等环节却容易掉以轻心。一旦监管机构对RSM的指定提出异议，所有下游开发工作便可能需要推倒重来；若项目涉及多国申报、各监管机构要求不一，RSM被质疑的风险则更为突出。

电话那头的客户遭遇的正是这一困境。更棘手的是，该项目是客户通过收购获得的，缺少原始技术包，而原供应商也已无力提供额外的支持。

未雨绸缪，提前半年预判风险

事实上，这场看似突发的“危机”，早在半年前就已被合全药业团队提前“预见”。

回到前一年的秋天，合全药业团队刚接手该项目的后期工艺开发及申报工作。基于丰富的申报经验和对全球法规的深刻理解，团队敏锐地识别出潜在的RSM风险。他们随即向客户做出了风险提示，并主动提出进行小规模验证作为预案，这一提议获得了客户的认可。

图片来源：123RF

当风险真正来临时，这份未雨绸缪的准备工作为后续争取时间奠定了重要的前置基础。

然而，真正的挑战并未解除。按照行业常规做法，完成类似工作通常需要7至9个月；即使有前置研究铺垫，往往也需要约6至7个月。

但客户当时给出的期限，只有4个月。

一体化平台，助力客户“抢回”时间

关键时刻，药明康德的一体化平台发挥了决定性作用。

在传统的项目执行中，流程是线性的——一步做完再做下一步，每个步骤必须等上一步完成才能启动，周期漫长。

但在药明康德的一体化平台上，流程被重构为高度并行的“并联”模式——工艺研发、分析支持、质量体系、生产执行、检测放行——每一个模块都在同步运转、无缝衔接，使项目周期被高度压缩。

面对缺少资料的原始技术包，接到这项任务的合全药业团队一边补全实验方案，一边搭建分析方法，同时无缝衔接研发、供应链与工厂，完成了上百项质量研究与工艺验证，为客户更新了申报所需的所有数据。

这一切能够实现，离不开药明康德一体化、端到端的CRDMO赋能平台。在这个平台上，多个技术平台为一体化协同提供了坚实支撑。比如，工艺工程团队运用实验设计（Design of Experiments，DoE）与分析模型，对工艺放大过程进行工程学风险评估与模拟，通过在极端条件下验证生产的稳健性，确保了工艺从克级实验室规模平稳放大至百公斤级生产规模；高通量研发平台则为大规模反应探索提供了硬件保障，实验室内的数台平行合成仪可同时启动十余个反应，极大提升了工艺研究效率；分析团队并行开发多种高难度分析方法，确保了检测与验证的同步推进……

若将公司全面的化学技术平台视为“硬实力”，那么精细化的项目管理和团队执行力便是不可或缺的“软实力”。在推进项目的过程中，为了完成这个看似“不可能完成的任务”，项目团队突破以周或天为单位的计划和管理方式，将项目执行和进度管理的颗粒度细化到“小时”级别。每一步生产、每一次检测和放行，都有精确的时间节点和明确的责任人。团队中每个责任人都清楚，自己的时间窗口只有几个小时。

图片来源：123RF

最终，团队仅用时3个月——比客户期待的周期还提前了一个月。

在速度超客户预期的同时，质量的稳健性一如既往：整个验证过程中，所有批次生产以零偏差交付，赢得了客户的高度认可。

这款新药随后顺利通过监管机构的审批并成功上市，持续服务于无数患者的临床需求。

客户的满意度转化为长久的信任：该项目的商业化生产一直保留在合全药业，客户也已成为公司的长期合作伙伴，并将更多后续项目委托于此。

此次针对客户RSM难题的超预期解决，看似是一次棘手的攻坚，实则是药明康德一体化CRDMO平台系统能力的集中体现。随着监管机构对RSM监管要求不断提高，药明康德也持续强化平台实力，进一步降低项目风险。公司可根据项目不同阶段和不同申报方案制定RSM风险管理与工艺开发策略，并具备从关键原料/起始物料工艺开发到生产的一体化能力，从而提升质量与灵活性。当监管机构对RSM定义提出异议时，团队能快速响应，例如在12周内完成QbD（Quality by Design）和PPQ（Process Performance Qualification），重新定义RSM。

总而言之，前瞻性的风险预判和前置研究、高度并行且无缝衔接的流程推进，以及精细的项目管理和团队执行力——每一个环节都不是孤立的亮点，而是平台长期积累与持续优化的必然结果，也是“一体化”模式的灵魂所在。

从常规周期大幅压缩至3个月，改变的远不止是交付周期，更是药明康德对客户承诺的扎实兑现。当新药最终通过审批、抵达患者手中时，所有的努力都汇聚成一个最朴素的答案——让天下没有难做的药，难治的病。

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).

A 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 Client 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 clients. 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.

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