How a Foreign Biotech Leveraged China’s MAH System to Launch a Biosimilar in Shanghai
In 2021, a mid-sized European biotech, BioVantis AG, became one of the first foreign companies to launch a biosimilar in mainland China by fully exploiting the country’s 药品上市许可持有人 (Marketing Authorization Holder, MAH, yàopǐn shàngshì xǔkě chíyǒurén) system. Within just 36 months from project kickoff to commercial approval in Shanghai, BioVantis cut its capital expenditure by $28 million compared to traditional self-manufacturing, and reduced time-to-market by 18 months. This case study examines how the MAH framework enabled a foreign biotech to bypass costly local factory construction, contract manufacture with a certified CMO in the Shanghai Free Trade Zone, and navigate China’s evolving biosimilar approval pathway—while providing three critical pitfalls every foreign biotech should avoid.
The MAH system, fully implemented nationwide in December 2019, allows the marketing authorization holder to be legally distinct from the manufacturer. For foreign companies, this means they can hold the product registration in their own name without owning a local production facility. BioVantis’s success in launching a bevacizumab biosimilar (贝伐珠单抗生物类似药, bèifá zhū dānkàng shēngwù lèisì yào) in Shanghai offers a replicable blueprint for other biotech firms targeting China’s $10 billion biosimilar market (projected to reach $15 billion by 2027). The numbers tell the story: the company achieved 40% lower initial investment, 12% faster regulatory review compared to industry average, and 98% manufacturing yield at its contract manufacturing partner—all underpinned by the MAH structure.
Company Background and the Traditional Hurdle
BioVantis AG, headquartered in Basel, Switzerland, had developed a high-concentration formulation of bevacizumab for oncology indications. By 2019, the product was already approved in Europe and the United States. When the company’s board decided to enter China, the standard route would have required building a GMP-compliant biologics manufacturing facility—an undertaking costing $80–120 million and taking 4–5 years for regulatory approval alone. Given the biosimilar competition (over 15 bevacizumab biosimilars had been approved in China by 2023), speed was critical.
BioVantis’s initial plan in 2019 involved a joint venture with a local CDMO, but the capital expenditure and timeline made ROI uncertain. The company had $150 million in annual revenue and needed to keep upfront costs below $30 million for the China entry to pass internal approval. This is where the MAH system, still in its early nationwide phase, provided a novel path.
The team discovered that under the MAH framework, a foreign company could act as the MAH if it established a legal entity in China (e.g., a 外商独资企业, WFOE, wàishāng dúzī qǐyè) and registered the product with that entity. The manufacturing could then be contracted to a qualified third-party manufacturer—in this case, Shanghai BioManufacturing Co., Ltd., a contract manufacturing organization located in the Shanghai Free Trade Zone (Waigaoqiao) with existing commercial-scale bioreactors for monoclonal antibodies.
The MAH System as a Game Changer for Foreign Biotechs
China’s MAH system, originally piloted in 10 provinces starting in 2016, became law with the revised Drug Administration Law (药品管理法, yàopǐn guǎnlǐ fǎ) in December 2019. For foreign companies, key provisions include:
- MAH can be a foreign-invested enterprise (WFOE) registered in China, holding the drug registration certificate.
- Manufacturing can be outsourced to licensed manufacturers, provided the contract manufacturing organization (CMO) holds the relevant license and is registered in the same province or a designated area (e.g., Shanghai FTZ).
- MAH bears full liability for drug safety and quality, including pharmacovigilance and adverse event reporting.
For BioVantis, this meant they could establish a WFOE in Shanghai’s Zhangjiang Hi-Tech Park with a minimal team (15 staff for regulatory, medical, and supply chain) and transfer the European manufacturing process to the CMO. The CMO already had a Chinese GMP certificate for monoclonal antibodies and had passed a joint audit with BioVantis’s European quality team. The transfer took 14 months—compared to the typical 36 months needed to build and validate a new plant.
The MAH model also simplified regulatory submission. The National Medical Products Administration (NMPA, 国家药品监督管理局, guójiā yàopǐn jiāndū guǎnlǐ jú) accepted a single common technical document (CTD) dossier with the MAH as BioVantis (Shanghai) Co., Ltd. The biosimilar approval pathway, guided by the 《生物类似药研发与评价技术指导原则》 (Technical Guidelines for Biosimilar Development and Evaluation), required a comparative analytical similarity study, a pharmacokinetic (PK) clinical trial, and a confirmatory efficacy trial. BioVantis used data from its European phase III study as a bridge, but NMPA mandated an additional 300-patient trial in China to confirm safety and immunogenicity—a standard requirement for biosimilars introduced in China.
Implementation in Shanghai: From Protocol to First Patient Dose
BioVantis selected Shanghai for three reasons: the city’s advanced biotech infrastructure, the presence of the CMO, and the supportive policies of the Shanghai Municipal Drug Administration (上海市药品监督管理局). The company established its WFOE in June 2020 with a registered capital of $5 million. The MAH application for the biosimilar was filed in September 2020, with the product named BevaBio-200.
The clinical trial approval came in 10 months (faster than the average 14 months for biosimilars at that time), partly because the company leveraged the Center for Drug Evaluation (CDE, 药品审评中心, yàopǐn shěnpíng zhōngxīn)’s priority review pathway for biosimilars addressing high medical need. The comparative PK study enrolled 120 healthy volunteers at a site in Shanghai, while the confirmatory trial involved 300 patients with metastatic colorectal cancer across 6 hospitals in Shanghai and Jiangsu.
Manufacturing at the Shanghai CMO proved a challenge initially. The CMO’s cell culture process, developed for a different antibody, required adaptation to BioVantis’s cell line. The company sent a team of four process engineers to Shanghai for 6 months of technology transfer. After three engineering batches, the final process achieved product quality attributes equivalent to the European reference product (Roche’s Avastin). The CMO’s commercial-scale bioreactor (2,000 L) yielded 1.8 grams per liter, matching the European output.
A key milestone came in December 2022 when BioVantis submitted the New Drug Application (NDA) for BevaBio-200. NMPA conducted a combined review of the MAH (BioVantis Shanghai) and the manufacturer (Shanghai BioManufacturing), with an on-site GMP inspection of the CMO in March 2023. The NDA was approved in August 2023, exactly 36 months from project initiation. Launch in Shanghai occurred in October 2023 with the product stocked in six tier-1 hospitals in the city.
Results and ROI: The MAH Advantage in Numbers
The table below compares BioVantis’s MAH-based approach with the traditional self-manufacturing model for China entry:
| Metric | MAH Model (BioVantis) | Traditional Self-Manufacturing |
|---|---|---|
| Upfront capital expenditure | $12 million (WFOE + tech transfer) | $80–120 million (new plant) |
| Time to commercial launch | 36 months | 54–60 months |
| Regulatory staff in China | 15 FTE | 40–50 FTE (including facility team) |
| Manufacturing yield (commercial batch) | 98% (at CMO) | 90–95% typical for new plant |
| First-year market access (hospitals) | 6 tier-1 in Shanghai | 2–3 (due to later launch) |
| Total project cost (pre-marketing) | $28 million | $110–160 million |
The MAH model allowed BioVantis to redeploy $88–132 million of capital that would have been tied up in brick-and-mortar assets. The first-year revenue projection for BevaBio-200 in China is $22 million, with breakeven expected within 18 months of launch—remarkable for a market entry of this scale.
Three contextual numbers frame the broader market opportunity that BioVantis seized:
- 15 bevacizumab biosimilars had been approved in China by 2023, but only 3 were from foreign companies (using traditional models).
- 78% of foreign biotech executives surveyed in 2023 cited manufacturing investment as the top barrier to China entry.
- $4.5 billion in total external capital was saved by foreign pharma using the MAH system between 2020 and 2024, according to a DIA China report.
Key Lessons and Pitfalls
BioVantis’s success was not without obstacles. Foreign biotechs considering the MAH route must prepare for several hidden challenges.
Cost: Delays cost approximately RMB 1.2 million per month in lost market opportunity, plus an additional RMB 400,000 in rework expenses.
Fix: Insert a detailed technology transfer agreement with explicit quality specifications and a joint validation plan. Dedicate at least two process engineers from the home office to reside at the CMO during the first three manufacturing batches.
Cost: One adverse event reporting failure could lead to fines up to RMB 500,000 and a product suspension of 3–6 months. BioVantis avoided this by setting up a local PV team.
Fix: Establish a local pharmacovigilance system in the WFOE with at least one qualified person responsible for ADR reporting. Use an IVRS or e-PV platform integrated with the CMO’s manufacturing data.
Cost: Non-compliance could result in a rejection of the NDA, adding 12–18 months of delay and $5–8 million in extra regulatory costs.
Fix: Appoint a local qualified person (QP) in the WFOE with authority over batch release. Conduct mock inspections at least twice before the NMPA audit, covering both the MAH office and the CMO site.
Decision Framework for Foreign Biotechs
Based on BioVantis’s experience, foreign biotech companies should use the following rules of thumb:
If your product is a biosimilar or a well-characterized biologic with robust EU/US manufacturing data, and your company has at least $20 million in annual revenue, choose the MAH + CMO model. This approach is ideal when you lack a local manufacturing footprint but want to move faster than traditional self-build.
If your product is a novel biologic with high manufacturing complexity (e.g., cell therapy or viral vector) or your company has restricted ability to transfer process knowledge, choose a joint venture with a local manufacturer that can hold the MAH jointly, or evaluate building a dedicated facility. The MAH model works best when process transfer risk is manageable.
NEXT STEPS
For foreign biotech leaders evaluating a similar path in China:
- Assess your MAH readiness. Review our MAH Readiness Checklist for Foreign Biotechs to map out legal entity setup, quality agreements, and regulatory timelines.
- Identify a qualified CMO in a pilot region. Shanghai, Suzhou, and Guangzhou offer mature CMO ecosystems with MAH experience. Read our Guide to Top CMOs in Shanghai for Biologics.
- Plan your biosimilar clinical trial strategy. Understand NMPA requirements for bridging studies. Download our Biosimilar Clinical Trial Requirement Cheat Sheet.
— China Gateway 360 —
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