Why controlled bottle freezing is a blast 为什么可控瓶冷冻如此有趣
The freezing of drug substances is a critical step in the manufacturing process, especially for high- value products like monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and other biologics. These substances are highly sensitive to temperature fluctuations, and improper freezing can compromise their stability, potency as well as overall quality. That’s why precision matters.
药物原料的冷冻是生产过程中至关重要的一步，尤其对于单克隆抗体（mAb）、抗体药物偶联物（ADC）和其他生物制剂等高价值产物而言更是如此。这些物质对温度波动高度敏感，冷冻不当会损害其稳定性、效力以及整体质量。因此，精准控制至关重要。
Although single-use bags are becoming more common as primary packaging for freezing applications, single-use bottles and even larger bulk packaging are still widely used for cold chain processes in both upstream and downstream bioprocessing. However, due to their geometry,
bottles have certain limitations that result in manufacturing challenges, such as uneven temperature distribution, risk of cryoconcentration, and limited scalability. Manufacturers require solutions that not only preserve product stability and integrity but also meet strict regulatory and operational requirements while fulfilling cost- efficiency in manufacturing processes. One of the greatest challenges is mastering the freezing process. By ensuring consistent, scalable and repeatable temperature profiles, the molecular structure of biologics is safeguarded. As the industry moves toward more flexible and efficient production environments, the role of advanced freezing technology for single-use bottles becomes increasingly important.
尽管一次性冷冻袋作为冷冻应用的一级包装越来越普遍，但在生物工艺的上游和下游冷链流程中，一次性瓶装甚至更大容量的散装包装仍然被广泛使用。然而，由于其几何形状的限制，瓶子存在一些局限性，导致生产过程中面临诸多挑战，例如温度分布不均、冷冻浓缩风险以及可扩展性有限。制造商需要能够保持产物稳定性和完整性、满足严格的监管和操作要求，同时兼顾成本效益的解决方案。其中一项巨大的挑战是掌握冷冻工艺。通过确保温度曲线的一致性、可扩展性和可重复性，可以保护生物制剂的分子结构。随着行业向更灵活高效的生产环境发展，优秀的一次性瓶冷冻技术的作用日益凸显。
Blast freezers have long been part of the solution, but innovation is redefining what’s possible. Next- generation systems like RoSS.BLST are setting new standards for bottle freezing in biopharma. They feature better temperature control and smarter designs with modular configurations.
速冻机长期以来一直是解决方案的一部分，但创新正在重新定义其应用范围。像 RoSS.BLST 这样的新一代系统正在为生物制药行业的瓶装冷冻树立新的标准。它们具有更精准的温度控制和更智能的模块化设计。
Figure 1: Human-machine interface of RoSS.BLST for controlled blast freezing 图 1：RoSS.BLST 可控速冻的人机界面
CONTROLLED | BLAST FREEZING PERFORMANCE 可控 | 速冻性能
Maintaining consistent and controlled freezing conditions is crucial to preserving the stability of sensitive biopharmaceutical products in bottles. RoSS.BLST uses a high-volume airflow system with 1800 m3/h to ensure even temperature distribution throughout the chamber. This supports gradual and uniform freezing, with temperatures reaching as low as -80 °C.
保持稳定可控的冷冻条件对于维持瓶装敏感生物制药产物的稳定性至关重要。RoSS.BLST 采用 1800 立方米/小时的大流量气流系统，确保整个冷冻室内的温度分布均匀。这有助于实现缓慢均匀的冷冻，温度可低至 -80 °C。
This performance of controlled cooling is consistent with study findings that highlight freezing rates of approximately -0.1 °C/min as optimal for minimizing cryoconcentration effects and preserving protein integrity.1 RoSS.BLST’s technical setup and design supports these recommended rates, helping to reduce stress on biologics during the freeze-thaw cycle, see figure 2.2
这种可控冷却性能与研究结果相符，该研究强调约 -0.1 °C/min 的冷冻速率是大限度减少冷冻浓缩效应并保持蛋白质完整性的优秀速率。 RoSS.BLST 的技术配置和设计支持这些推荐的冷冻速率，有助于减少生物制剂在冻融循环过程中受到的应力（见图 2.2）。
Compared to static freezing methods, the blast approach offers improved thermal conductivity and more uniform solute and protein distribution, and is therefore less prone to increased cryoconcentration levels inside single-use bottles. Comparisons show that airflow-based systems better manage temperature gradients than static freezers, which is particularly relevant for protein stability and overall product quality.
与静态冷冻方法相比，高速气流冷冻方法具有更高的导热性和更均匀的溶质和蛋白质分布，因此不易导致一次性瓶内冷冻浓缩水平升高。对比结果表明，气流式系统比静态冷冻机更能有效地控制温度梯度，这对于蛋白质稳定性和整体产物质量尤为重要。
Median freeze run temperature curve (n = 192 bottles) 中位冷冻运行温度曲线（n = 192 瓶）
Figure 2: Exemplary controlled-rate freeze run of 192 bottles down to -80 °C with RoSS.BLST
图 2：使用 RoSS.BLST 对 192 瓶样品进行控制速率冷冻至 -80 °C 的示例实验
MULTIFUNCTIONAL | FREEZE, THAW, SHAKE 多功能 | 冷冻、解冻、摇晃
Beyond freezing, RoSS.BLST also supports a range of functions that enhance process control and operational flexibility. Both freezing and thawing can be carried out at controlled rates, which is particularly important for maintaining the stability of temperature-sensitive biologics.
除了冷冻功能外，RoSS.BLST 还支持一系列增强工艺控制和操作灵活性的功能。冷冻和解冻均可按控制速率进行，这对于维持温度敏感型生物制剂的稳定性尤为重要。
During thawing, integrated shaking is available and often preferred, as it facilitates uniform temperature distribution throughout the container. This is critical for preventing localized hot or cold spots that can lead to uneven reconstitution, protein aggregation, or phase separation. Shaking also helps minimize the formation of concentration gradients, especially in high-viscosity or freeze-concentrated solutions.Together, controlled thawing and active agitation reduce the risk of denaturation and ensure consistent product quality across the entire batch.
在解冻过程中，系统集成了摇动功能，并且通常是优选择，因为它有助于容器内温度均匀分布。这对于防止局部出现过热或过冷点至关重要，这些局部过热或过冷点会导致复溶不均匀、蛋白质聚集或相分离。摇动还有助于大限度地减少浓度梯度的形成，尤其是在高粘度或冷冻浓缩溶液中。控制解冻和主动搅拌相结合，可降低变性风险，并确保整个批次产物质量的一致性。
The system is designed to meet qualification and validation requirements in line with GMP, FDA, and EU Annex 1 standards. This supports regulatory compliance across different markets and simplifies documentation during tech transfer or scale-up. It can also be integrated into Manufacturing Execution Systems (MES) and Enterprise Resource Planning (ERP) platforms, allowing for automated data logging and process control.
该系统旨在满足符合 GMP、FDA 和欧盟 Annex 1 标准的验证和确认要求。这有助于在不同市场实现合规性，并简化技术转移或放大生产过程中的文件工作。它还可以集成到制造执行系统(MES) 和公司资源计划 (ERP) 平台中，从而实现自动化数据记录和过程控制。
COMPACT | LOW FOOTPRINT PER LITER 体积小巧 | 每升占地面积小
Cleanroom space is often limited and costly. This makes space utilization a key consideration in biopharmaceutical production.
洁净室空间通常有限且成本高昂。因此，空间利用率是生物制药生产中的关键考量因素。
With this in mind, RoSS.BLST is designed to offer an exceptional balance between footprint and loading capacity.With a usable chamber volume of 2.5 m3 (88.29 ft3), the system has the best-in-class volume- to-footprint ratio and fits comfortably into compact environments. It can hold up to 192 bottles with 2 L fill volumes each, enabling manufacturers to maximize productivity while making efficient use of limited facility space.
鉴于此，RoSS.BLST 的设计旨在实现占地面积和装载能力之间的优秀平衡。该系统拥有 2.5 立方米（88.29 立方英尺）的可用腔室容积，具备同类产物中优秀的容积/占地面积比，可轻松适应紧凑型环境。它最多可容纳 192 瓶，每瓶容量为 2 升，使制造商能够在有限的设施空间内大限度地提高生产效率。
Additionally, the system’s design incorporates the temperature control unit into the main housing, eliminating the need for separate installations and simplifying layout planning. For facilities aiming to optimize spatial efficiency without having to compromise batch size, this configuration offers a practical solution.
此外，该系统将温度控制单元集成到主壳体中，无需单独安装，从而简化了布局规划。对于希望在不影响批次大小的前提下优化空间效率的工厂而言，这种配置提供了一种切实可行的解决方案。
SUSTAINABLE | NATURAL REFRIGERANTS 可持续 | 天然制冷剂
Refrigeration systems in pharmaceutical environments are increasingly expected to meet sustainability standards without compromising safety or performance. RoSS.BLST operates with the natural refrigerants propane (R290) and ethane (R170). Their refrigerant load of < 500g helps reduce environmental impact while maintaining system integrity. Thanks to the low refrigerant charge, the blast freezer can be placed in standard rooms without the need for specific safety measures or cleanroom grade precautions, i.e. no ATEX air-venting system is required.
在制药环境中，制冷系统越来越需要满足可持续发展标准，同时确保安全性和性能不受影响。RoSS.BLST 采用天然制冷剂丙烷 (R290) 和乙烷 (R170)。其制冷剂充注量低于 500 克，有助于减少对环境的影响，同时保持系统完整性。由于制冷剂充注量低，该速冻机可放置在标准房间内，无需采取特殊的安全措施或洁净室级别的防护措施，例如无需 ATEX 防爆通风系统。
The blast freezer’s hermetically sealed construction complies with EN378 and ISO5149 standards. It is equipped with gas detection systems that provide an added layer of protection in case of refrigerant leakage while also supporting operational safety.
该速冻机采用密封结构，符合 EN378 和 ISO5149 标准。它配备气体检测系统，可在制冷剂泄漏时提供额外的保护，同时确保运行安全。
This approach allows for more installation flexibility in manufacturing facilities and aligns with current environmental and safety regulations. It reflects the industry’s broader trend toward minimizing the ecological footprint of temperature-controlled processes.
这种设计方案提高了生产设施的安装灵活性，并符合当前的环保和安全法规。它体现了整个行业致力于大限度减少温控工艺对环境影响的趋势。
FLEXIBLE | MODULAR INTERIOR 灵活 | 模块化内饰In biopharmaceutical multi-product facilities, the efficient and safe handling of a variety of packaging formats presents significant challenges.
在生物制药多产物生产设施中，高效安全地处理各种包装规格是一项重大挑战。
RoSS.BLST is designed to accommodate different types of bulky primary packaging, ranging from standard bottles to larger 2D or 3D containers. The blast freezer has a modular shelving system, with adjustable shelves to fit different containers of varying sizes. This enables a single unit to handle multiple products and workflows, providing the flexibility required for contract development and manufacturing organizations (CDMOs), where switching between formats is a routine part of operations.
RoSS.BLST 的设计旨在容纳不同类型的大体积初级包装，从标准瓶到更大的二维或三维容器。该速冻机采用模块化货架系统，可调节的货架能够适应不同尺寸的容器。这使得单个设备即可处理多种产物和工作流程，为合同研发生产机构 (CDMO) 提供了所需的灵活性，因为在这些机构中，包装规格的切换是日常操作的一部分。
The interior can be reconfigured to accommodate changing production volumes or packaging requirements without additional equipment so it also supports scalable bottle-based processes. This simplifies planning and improves the overall utilization of available resources.
其内部结构无需额外设备即可重新配置，以适应不断变化的生产量或包装要求，因此也支持可扩展的瓶装工艺。这简化了规划，并提高了可用资源的整体利用率。
Figure 4: Modular interior design for single-use bottles and other primary packaging 图 4：一次性瓶子和其他初级包装的模块化内部设计
From bottlenecks to breakthroughs 从瓶颈到突破
While blast freezers are well-established in biopharmaceutical manufacturing, challenges remain, especially in efficiently and consistently freezing single-use bottles without compromising product integrity.
尽管速冻机在生物制药生产中应用广泛，但仍存在一些挑战，尤其是在高效、稳定地冷冻一次性瓶装产物而不损害其完整性方面。
RoSS.BLST fits right into this niche. It is more than just another blast freezer, as it combines high- performance freezing with modular design features that support compatibility with different container types, scalability and automation.
RoSS.BLST 正好满足了这一需求。它不仅仅是一台普通的速冻机，它将高性能冷冻与模块化设计相结合，支持与不同类型容器的兼容性、可扩展性和自动化。
Developed by Single Use Support, this blast freezer is part of a modular, end-to-end solution for handling bottles that addresses the entire fluid and cold chain management process (see Figure 6). Prior to freezing, the process incorporates aseptic filling using IRIS bottle assemblies and RoSS.FILL aseptic fillers, which enable closed-system fluid management and support efficient and safe filling into bottles. Crucially, it also includes protective single-use consumables that maximize product safety and integrity at every step. As part of this system, Bottle RoSS provides a robust secondary packaging solution that safeguards the tubing and assemblies on bottle caps from damage during cold chain handling. Its design allows for secure handling during automated freezing workflows and is compatible with most single-use bottles.
这款速冻机由 Single Use Support 公司开发，是模块化端到端瓶装解决方案的一部分，该方案涵盖了整个流体和冷链管理流程（见图 6）。在冷冻之前，该流程采用 IRIS 瓶组件和 RoSS.FILL 无菌灌装机进行无菌灌装，从而实现封闭式流体管理，并支持高效、安全地灌装到瓶中。至关重要的是，它还包括保护性的一次性耗材，可在每个步骤大限度地保障产物的安全性和完整性。作为该系统的一部分，Bottle RoSS 提供了一种可靠的二级包装解决方案，可在冷链处理过程中保护瓶盖上的管路和组件免受损坏。其设计确保在自动化冷冻流程中安全操作，并兼容大多数一次性瓶子。
Manufacturers can gain enhanced control,increased throughput, and superior product quality with an advanced blast freezer that addresses existing gaps.
这款优秀的速冻机能够弥补现有工艺的不足，帮助制造商获得更强的控制力、更高的产量和更优秀的产物质量。
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Figure 5: Robust secondary packaging for bottle tubing with Bottle RoSS 图 5：采用 Bottle RoSS 的坚固型瓶管二级包装
Figure 6: End-to-end fluid and cold chain process for bottles图 6：瓶装液体和冷链的端到端流程
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