3. 共同研发方-上海泉生
Asia Cell & Gene Therapeutics Group Due Diligent Data Room
位于中国上海的aCGT合作研发方-泉生公司专注于：货架型、通用型细胞与基因治疗(CGT)新药研发、中国临床试验样品生产、中国NMPA注册申报、中国多中心临床试验。
The aCGT's co-development partner, Quansheng Company, located in Shanghai, China, focuses on: the development of off-the-shelf, universal cell and gene therapy (CGT) novel therapeutics, the manufacturing of clinical trial materials for studies conducted in China, China NMPA regulatory filings, and the conduct of China-based multi-center clinical trials.
上海泉生部门人员架构图
Independent Directors: ??
Non-Independent Directors: ??
Full-Time Employees - Shanghai Quansheng: 40
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Disclosure of look-through individual shareholder information involves personal privacy and will be provided separately offline.
《药品生产质量管理规范》（Good Manufacturing Practice of Medical Products，GMP）是药品生产和质量管理的基本准则，适用于药品制剂生产的全过程和原料药生产中影响成品质量的关键工序。该规范自2011年3月1日起施行，制定依据为《中华人民共和国药品管理法》及其实施条例，旨在规范药品生产质量管理，降低污染、交叉污染及混淆、差错风险，确保持续稳定生产符合要求的药品。
Good Manufacturing Practice of Medical Products (GMP) is the basic criterion for pharmaceutical production and quality management, applicable to the entire process of pharmaceutical preparation production and the key processes affecting the quality of finished products in bulk drug production. This specification has been implemented since March 1, 2011, formulated in accordance with the Drug Administration Law of the People's Republic of China and its implementing regulations, aiming to standardize the quality management of pharmaceutical production, reduce the risks of contamination, cross-contamination, confusion and errors, and ensure the continuous and stable production of pharmaceuticals that meet the requirements.
自2019年起取消药品GMP认证，改为通过动态监管强化企业持续合规责任，药品监督管理部门实施药品生产质量管理规范符合性检查，将五年一次的认证检查调整为随时动态检查，同时建立融合检查、合并检查机制。这是一个从“静态认证”到“动态持续合规”的根本性转变。
The pharmaceutical GMP certification has been cancelled since 2019, and instead, the enterprise's continuous compliance responsibility has been strengthened through dynamic supervision. The drug regulatory department conducts compliance inspections on the Good Manufacturing Practice for Pharmaceutical Production, adjusting the five-year certification inspection to random dynamic inspections, and establishing a mechanism of integrated inspections and combined inspections at the same time. This is a fundamental transformation from "static certification" to "dynamic continuous compliance".
在新药获批上市前，生产车间必须通过药品GMP符合性检查。根据企业的具体情况，主要涉及以下两种路径，它们决定了检查的启动方式和时机：
Before a new drug is approved for marketing, the production workshop must pass the GMP compliance inspection for pharmaceuticals. According to the specific situation of the enterprise, it mainly involves the following two paths, which determine the initiation method and timing of the inspection:
| 检查路径类型 Inspection Path Type | 适用情形 Applicable Situations | 申请主体与检查时机 Applicant and Inspection Timing | 特点与说明 Characteristics and Explanations |
|---|---|---|---|
| 依申请检查 Application-based Inspection | 1.创新药/生物制品申报上市：这是最核心的情形。 2.新建/改建/扩建车间或生产线（已上市药品）。 | 由药品上市许可持有人（MAH）主动向省级药监部门申请。申请时间通常在新药上市注册申请阶段。 | 必须申请。对于生物创新药，这是上市前必须完成的环节。 |
| 依职责检查 Duty-based Inspection | 药监部门根据法规和风险评估主动发起的检查。 | 由药品监督管理部门依职责发起并组织实施。 | 无论是否上市，药监部门会定期（如高风险企业每年）和不定期对生产企业进行检查，确保持续合规。 |
泉生公司目前未达到“新药上市注册申请阶段”，因此未向省级药监部门申请GMP符合性检查。
Quansheng Company has not yet reached the "new drug marketing registration application stage", so it has not applied to the provincial drug regulatory department for GMP compliance inspection.
图1：厂房外景 (GMP Workshop Overview)
图2：更衣室 (Workshop Layout Plan)
图3：一般洁净走廊A (Clean Area Grade Standard)
图4：一般洁净走廊B (Production Equipment Configuration)
图5：B级洁净走廊 (Quality Control Area)
图6：B级细胞培养室 (Material Storage Area)
图7：QC实验室 (Air Filtration System)
图8：QC理化实验室 (Waste Disposal Process)
图9：QC流式细胞术检测室 (Personnel Entry Procedure)
图10：研发C级洁净车间和临床B级洁净车间平面图 (Temperature & Humidity Control)
图11：质控区域平面图 (GMP Compliance Document)
泉生公司的办公室、非GMP实验室及GMP车间的长期租赁合同 Long-term lease contract for the offices, non-GMP laboratory, and GMP workshop of Quansheng Company：
人脐带间充质干细胞注射液原液、成品生产均在上海泉生生物科技有限公司车间完成。上海泉生生物科技有限公司车间是参照GMP标准建造的，生产的主要设备（CO₂培养箱、离心机等）均采购自国内外主流厂家如Thermo Fisher、Beckman及BD等，每年进行周期性设备计量工作，能够有效保证设备性能。
The drug substance and finished product of Human Umbilical Cord Mesenchymal Stem Cell Injection are both manufactured in the facility of Shanghai Quansheng Biotechnology Co., Ltd. The facility is constructed in accordance with GMP standards. Key production equipment (e.g., CO₂ incubators, centrifuges) is sourced from leading domestic and international manufacturers such as Thermo Fisher, Beckman, and BD. Periodic metrological calibration is performed annually to effectively ensure equipment performance.
| 设备 | 厂家 | 型号 | 关键参数 | 批量范围 | 工艺步骤 | 工作原理 | 匹配性 |
|---|---|---|---|---|---|---|---|
| 生物安全柜 Biological Safety Cabinet | 苏净安泰 Suzhou Antai | BSC-1300IIA2 | II级A2型 Class II, Type A2 | 连续使用 Continuous | 复苏、传代 Thawing, Subculture | 负压+HEPA过滤保护人员与样品 | 满足 Satisfied |
| CO₂培养箱 CO₂ Incubator | Thermo Fisher | 3111 | Temp: RT+5–60℃ CO₂: 0–20% | 连续使用 | 细胞培养 | 红外控CO₂，水套恒温 | 满足 |
| 高速冷冻离心机 | Beckman Coulter | Avanti JXN-26 | 26,000 rpm 76,744 ×g | 1–2 L | 细胞收集 | 密度分离 | 满足 |
| 超低温冰箱 | Thermo Fisher | TSX70086 | -50 ~ -86℃ | 连续使用 | 细胞冻存 | 变频压缩机 | 满足 |
| 程序降温仪 | BioLife Solutions | CryoMed™ CM1000 | -0.1 ~ -100℃/min | 1–2 L | 程序冻存 | 控速防冰晶 | 满足 |
| 液氮罐 | Chart MVE | XC47/11-6 | 47 L 0.38 L/day evap. | 连续使用 | 长期储存 | 真空绝热，-196℃ | 满足 |
| 细胞工厂 | Nunc (Thermo) | CF100 | 10层，总表面积6320 cm² | 1–2 批次 | 大规模扩增 | 多层贴壁培养 | 满足 |
| 蠕动泵 | Watson-Marlow | 520Du | 流速：0.05–500 mL/min | 连续使用 | 培养基灌注 | 滚轮挤压软管输送液体 | 满足 |
| pH计 | Mettler Toledo | SevenExcellence | 精度 ±0.001 pH | 连续使用 | 培养基质控 | 玻璃电极电位法 | 满足 |
| 电子天平 | Sartorius | Entris224-1S | 量程 220 g 精度 0.1 mg | 连续使用 | 称量辅料 | 电磁力平衡传感器 | 满足 |
| 纯水系统 | Millipore | Milli-Q® IQ 7000 | 电阻率 ≥18.2 MΩ·cm | 连续使用 | 配制溶液 | RO + EDI + UV + 超滤 | 满足 |
| 冻干机 | SP Scientific | Virtis AdVantage | 冷阱温度 -85℃ 最大凝冰量 10 kg | 1–2 L | 冻干制剂 | 升华干燥去除水分 | 满足 |
| 在线TOC分析仪 | Sievers | M9 | 检测限 0.03 ppb C | 连续监测 | 注射用水监控 | 紫外过硫酸盐氧化法 | 满足 |
| 环境监测系统 | Lighthouse | ISO-MAP | 粒子计数、温湿度、压差 | 连续监测 | 洁净区监控 | 实时数据采集与报警 | 满足 |
| 设备 | 厂家 | 型号 | 关键参数 | 检测项目 | 工作原理 |
|---|---|---|---|---|---|
| 流式细胞仪 | BD Biosciences | FACSCanto™ II | 488/633 nm ≥6色 | CD73/90/105等 | 荧光抗体+激光检测 |
| 全自动细胞计数仪 | Bio-Rad | TC20™ | 5×10⁴–1×10⁷ cells/mL | 浓度与活率 | 台盼蓝染色 |
| 酶标仪 | BioTek | Synergy H1 | Abs/FL/LUM 230–999 nm | IL-6, VEGF等ELISA | 光信号定量 |
| 倒置显微镜 | Olympus | CKX53 | 40×–400× 相差+荧光 | 形态与污染 | 底部照明观察贴壁细胞 |
| PCR仪 | Applied Biosystems | QuantStudio™ 5 | qPCR 96/384孔 | 支原体检测 | 实时荧光扩增 |
| 微生物鉴定系统 | bioMérieux | VITEK® 2 Compact | GN/GP/YST卡 | 阳性菌鉴定与药敏 | 比浊+荧光分析 |
| 内毒素检测仪 | Lonza | PyroGene™ | 动态显色法 检测限 0.005 EU/mL | 细菌内毒素 | 鲎试剂激活显色反应 |
| 残余DNA检测试剂盒配套设备 | Promega | QuantiFluor® | 荧光检测 灵敏度 1 pg/μL | 宿主细胞DNA残留 | PicoGreen荧光染料结合dsDNA |
| 高效液相色谱仪 | Agilent | 1260 Infinity II | 压力 ≤600 bar 波长 190–950 nm | 蛋白含量、杂质分析 | 色谱柱分离+UV检测 |
| 电泳系统 | Bio-Rad | Mini-PROTEAN® Tetra | 电压 10–500 V 电流 4–400 mA | 蛋白纯度、分子量 | 电场驱动蛋白迁移 |
| 渗透压仪 | Gonotec | Osmomat® 3000 | 测量范围 0–3000 mOsm/kg | 制剂渗透压 | 冰点下降法 |
| 不溶性微粒检测仪 | Pamas | S40 | 检测粒径 ≥2 μm | 注射液微粒 | 光阻法计数颗粒 |
