新藥研發周期長、環節眾多，任何一個環節都至關重要且充滿變數，而挑戰有時恰恰來自那些容易被忽視的環節。

幾年前的一個清晨，藥明康德子公司合全藥業的一間會議室里，一場臨時會議正在進行。

客戶剛剛來電：他們一款正在申報上市的小分子新藥，受到了歐洲藥品管理局（EMA）的質疑，問題出在了監管起始物料（Regulatory Starting Materials，RSM）上。

監管起始物料是原料藥注冊申報工藝描述的起點，也是藥品生產質量管理規范（GMP）實施和變更管理的起點。它可以是該原料藥結構中重要組成部分的原材料、中間體或其他原料藥，其所含的雜質及后續反應中生成的轉化產物，都有可能被帶入最終的原料藥中。因此，RSM的選擇與質量控制，是整個原料藥開發的重要組成部分。

在制定CMC方案時，人們的關注點往往集中于藥品開發供應鏈的下游，如原料藥的后期工藝直至藥品上市環節，而對上游的RSM等環節卻容易掉以輕心。一旦監管機構對RSM的指定提出異議，所有下游開發工作便可能需要推倒重來；若項目涉及多國申報、各監管機構要求不一，RSM被質疑的風險則更為突出。

電話那頭的客戶遭遇的正是這一困境。更棘手的是，該項目是客戶通過收購獲得的，缺少原始技術包，而原供應商也已無力提供額外的支持。

未雨綢繆，提前半年預判風險

事實上，這場看似突發的“危機”，早在半年前就已被合全藥業團隊提前“預見”。

回到前一年的秋天，合全藥業團隊剛接手該項目的后期工藝開發及申報工作。基于豐富的申報經驗和對全球法規的深刻理解，團隊敏銳地識別出潛在的RSM風險。他們隨即向客戶做出了風險提示，并主動提出進行小規模驗證作為預案，這一提議獲得了客戶的認可。

圖片來源：123RF

當風險真正來臨時，這份未雨綢繆的準備工作為后續爭取時間奠定了重要的前置基礎。

然而，真正的挑戰并未解除。按照行業常規做法，完成類似工作通常需要7至9個月；即使有前置研究鋪墊，往往也需要約6至7個月。

但客戶當時給出的期限，只有4個月。

一體化平臺，助力客戶“搶回”時間

關鍵時刻，藥明康德的一體化平臺發揮了決定性作用。

在傳統的項目執行中，流程是線性的——一步做完再做下一步，每個步驟必須等上一步完成才能啟動，周期漫長。

但在藥明康德的一體化平臺上，流程被重構為高度并行的“并聯”模式——工藝研發、分析支持、質量體系、生產執行、檢測放行——每一個模塊都在同步運轉、無縫銜接，使項目周期被高度壓縮。

面對缺少資料的原始技術包，接到這項任務的合全藥業團隊一邊補全實驗方案，一邊搭建分析方法，同時無縫銜接研發、供應鏈與工廠，完成了上百項質量研究與工藝驗證，為客戶更新了申報所需的所有數據。

這一切能夠實現，離不開藥明康德一體化、端到端的CRDMO賦能平臺。在這個平臺上，多個技術平臺為一體化協同提供了堅實支撐。比如，工藝工程團隊運用實驗設計（Design of Experiments，DoE）與分析模型，對工藝放大過程進行工程學風險評估與模擬，通過在極端條件下驗證生產的穩健性，確保了工藝從克級實驗室規模平穩放大至百公斤級生產規模；高通量研發平臺則為大規模反應探索提供了硬件保障，實驗室內的數臺平行合成儀可同時啟動十余個反應，極大提升了工藝研究效率；分析團隊并行開發多種高難度分析方法，確保了檢測與驗證的同步推進……

若將公司全面的化學技術平臺視為“硬實力”，那么精細化的項目管理和團隊執行力便是不可或缺的“軟實力”。在推進項目的過程中，為了完成這個看似“不可能完成的任務”，項目團隊突破以周或天為單位的計劃和管理方式，將項目執行和進度管理的顆粒度細化到“小時”級別。每一步生產、每一次檢測和放行，都有精確的時間節點和明確的責任人。團隊中每個責任人都清楚，自己的時間窗口只有幾個小時。

圖片來源：123RF

最終，團隊僅用時3個月——比客戶期待的周期還提前了一個月。

在速度超客戶預期的同時，質量的穩健性一如既往：整個驗證過程中，所有批次生產以零偏差交付，贏得了客戶的高度認可。

這款新藥隨后順利通過監管機構的審批并成功上市，持續服務于無數患者的臨床需求。

客戶的滿意度轉化為長久的信任：該項目的商業化生產一直保留在合全藥業，客戶也已成為公司的長期合作伙伴，并將更多后續項目委托于此。

此次針對客戶RSM難題的超預期解決，看似是一次棘手的攻堅，實則是藥明康德一體化CRDMO平臺系統能力的集中體現。隨著監管機構對RSM監管要求不斷提高，藥明康德也持續強化平臺實力，進一步降低項目風險。公司可根據項目不同階段和不同申報方案制定RSM風險管理與工藝開發策略，并具備從關鍵原料/起始物料工藝開發到生產的一體化能力，從而提升質量與靈活性。當監管機構對RSM定義提出異議時，團隊能快速響應，例如在12周內完成QbD（Quality by Design）和PPQ（Process Performance Qualification），重新定義RSM。

總而言之，前瞻性的風險預判和前置研究、高度并行且無縫銜接的流程推進，以及精細的項目管理和團隊執行力——每一個環節都不是孤立的亮點，而是平臺長期積累與持續優化的必然結果，也是“一體化”模式的靈魂所在。

從常規周期大幅壓縮至3個月，改變的遠不止是交付周期，更是藥明康德對客戶承諾的扎實兌現。當新藥最終通過審批、抵達患者手中時，所有的努力都匯聚成一個最樸素的答案——讓天下沒有難做的藥，難治的病。

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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