Manufacturing challenges 制造挑战Ensuring product quality 确保产品质量Biologics are susceptible to physical and chemical degradation. Even slight temperature fluctuations can lead to protein denaturation or aggregation, reducing efficacy. Freeze-thaw cycles of biologics in large-volume formats are often required for their storage and transport; however this process can compromise product integrity. To mitigate these risks, manufacturers must rely on validated processes and advanced monitoring systems that maintain consistent conditions throughout the freezing and thawing process.
生物制剂易受物理和化学因素的影响而降解。即使是轻微的温度波动也可能导致蛋白质变性或聚集，从而降低疗效。大体积生物制剂的储存和运输通常需要反复冻融；然而，这一过程可能会损害产品的完整性。为了降低这些风险，生产商必须依赖经过验证的工艺和监控系统，以确保在整个冻融过程中保持条件的一致性。
Selecting primary packaging 选择初级包装Single-use containers, primarily bags or bottles, are the most common types of containers used to transport and store biologics, but each type of container has its own limitations. Bags offer flexibility and facilitate aseptically closed systems. However, they are prone to damage due to mechanical stress and can break if not adequately protected when in a frozen state. Rigid containers also tend to be bulky, which means they take a long time to freeze and thaw. This can compromise product quality. Bottles provide better structural integrity but can limit scalability and require specialized handling equipment. The choice of primary packaging used during freezing often determines the subsequent cold chain management technologies employed. This is because not all cold chain management solutions are compatible with all types of primary packaging.
一次性容器，主要是瓶子或袋子，是运输和储存生物制剂容器类型，但每种容器都有其自身的局限性。袋子容器具有灵活性，便于建立无菌封闭系统。然而，它们容易因机械应力而损坏，如果在冷冻状态下保护不当，则可能破裂。硬质容器通常体积较大，这意味着它们需要较长的冻融时间。这可能会影响产品质量。瓶装容器具有更好的结构完整性，但会限制其规模化生产，并且需要专门的操作设备。冷冻过程中使用的初级包装的选择通常决定了后续冷链管理技术的应用。这是因为并非所有冷链管理解决方案都与所有类型的初级包装兼容。
Incompatible processes 不兼容的工艺The use of single-use bags can constrain process flexibility because of equipment incompatibilities and vendor lock-in. Therefore, scalable biopharmaceutical manufacturing solutions must support variable batch volumes while minimizing the need for substantial facility reconfiguration. Bag-independent and modular solutions are thus increasingly popular. Combining modular systems with automation can streamline workflows, reduce the need for manual intervention, and minimize contamination risks, as recommended in EU GMP Annex 1. Ultimately, an end-to-end process that is compatible with every step of cold chain management – from filling and freezing to storage and thawing – ensures a smooth transition, while also facilitating compliance with relevant quality control standards, such as EU GMP Annex 1.
由于设备不兼容和供应商锁定，使用一次性袋子会限制工艺的灵活性。因此，可扩展的生物制药生产解决方案必须支持不同批次量，同时减少对设施进行大规模重新配置的需求。因此，独立于袋子的模块化解决方案越来越受欢迎。将模块化系统与自动化相结合可以简化工作流程，减少人工干预，并降低污染风险，正如欧盟GMP附录1所建议的那样。最终，一个与冷链管理的每个步骤（从灌装和冷冻到储存和解冻）都兼容的端到端流程，可以确保平稳过渡，同时也有助于符合相关的质量控制标准，例如欧盟GMP附录1。
Sustainable processes 可持续过程Cold chain operations are energy intensive, driven largely by the power requirements of freezers and temperature-controlled storage units. Optimizing freezing profiles and investing in energy-efficient equipment can help reduce the environmental impact of these operations. The use of fluorinated gases, also known as F-gases, is gradually being phased out, with the European Union setting a goal for a complete phase-out by 2050.
3 They are being replaced by natural gases and air-cooled technologies with much lower global warming potential (GWP) than F-gases.
冷链操作是能源密集型的，这主要是由于冷冻机和温控存储单元的电力需求造成的。优化冷冻工艺流程并投资节能设备有助于减少这些作业对环境的影响。含氟气体（也称氟化气体）的使用正在逐步淘汰，欧盟的目标是在2050年前淘汰。³取而代之的是天然气和空气冷却技术，这些技术的变暖潜值（GWP）远低于氟化气体。
Figure 2: Reductions in product quality during cold chain management processes are a major concern for biopharmaceutical manufacturers
图 2：冷链管理过程中产品质量下降是生物制药生产商关注的主要问题。
The behavior of biologics during freezing生物制品在冷冻过程中的行为When biologics are frozen, several important changes occur that can influence their stability and efficacy. A thorough understanding of these behaviors is essential for preserving long-term product quality and efficacy.
生物制剂冷冻保存期间会发生一些重要变化，这些变化会影响其稳定性和疗效。深入了解这些变化对于保持产品的长期质量和疗效至关重要。
What happens when freezing biologics? 生物制剂冷冻后会发生什么？Proteins are thermally unstable molecules, and their native structure depends on a delicate balance of interactions within the protein itself and between the protein and surrounding components, such as solvents. When a protein solution is frozen, the temperature of the solution initially decreases steadily as the heat is removed. As the temperature continues to decrease, the solution can become super-cooled, which means that it drops below its normal freezing point without immediately forming ice. However, at a certain temperature, ice begins to form; this is known as
ice nucleation. Once ice starts to form, the temperature briefly stabilizes because energy is being used to change the liquid protein solution into solid ice, not to lower the temperature further. This stage is known as the
phase transition. After most of the liquid has turned to ice, the temperature begins to decrease again as more heat is removed, and the solution becomes completely solid.
蛋白质是热稳定性较差的分子，其天然结构依赖于蛋白质内部以及蛋白质与周围成分（例如溶剂）之间相互作用的微妙平衡。当蛋白质溶液被冷冻时，随着热量的移除，溶液的温度最初会稳定下降。随着温度持续下降，溶液会变得过冷，这意味着它的温度会降至正常冰点以下，但不会立即形成冰。然而，在达到一定温度后，冰开始形成；这被称为冰核形成。一旦冰开始形成，温度会短暂稳定下来，因为能量被用于将液态蛋白质溶液转化为固态冰，而不是用于进一步降低温度。这个阶段被称为相变。当大部分液体转化为冰后，随着更多热量的移除，温度再次开始下降，溶液最终凝固。
Figure 3: The behavior of biologics during the freezing process 图 3：生物制品在冷冻过程中的行为
Figure 4: Ice crystallization at each step in the freezing process
What physical changes impact protein stability during freezing?冷冻过程中哪些物理变化会影响蛋白质的稳定性？Freezing and thawing can alter how proteins interact with their environment, which in turn can reduce their stability. One of the most important effects is cryoconcentration.
4,5 When pharmaceutical products are frozen in large batches, ice forms as the temperature decreases; this removes water that normally hydrates and stabilizes proteins. As a result, proteins and other formulation components become concentrated in the remaining unfrozen solution. The loss of protective water and the increased concentration of other ingredients can destabilize proteins, leading to aggregation, partial unfolding, or unwanted interactions with formulation components or container surfaces.
冻融过程会改变蛋白质与其环境的相互作用方式，进而降低其稳定性。其中最重要的影响之一是冷冻浓缩。当药品批量冷冻时，随着温度降低会形成冰；冰会带走通常用于水合和稳定蛋白质的水分。因此，蛋白质和其他制剂成分会在剩余的未冻结溶液中浓缩。保护性水分的损失和其他成分浓度的增加会导致蛋白质不稳定，进而引起聚集、部分展开或与制剂成分或容器表面发生不必要的相互作用。
Cryoconcentration can introduce several additional destabilizing effects. As freezing progresses, the solution becomes more viscous, and the rates of freezing and thawing influence how long these altered conditions persist. Ice formation can also trap small air bubbles, which may further disrupt protein structure and reduce stability. Another key factor is the formation of ice-liquid interfaces.
5 Proteins that adsorb to these interfaces can undergo structural changes or denaturation; therefore, control of the cooling rate is critical. More rapid freezing generally produces smaller ice crystal s and results in a larger ice-liquid interface. This can help limit the unwanted crystallization of buffering components and support maintenance of solution pH.
冷冻浓缩还会引入其他几种不稳定因素。随着冷冻的进行，溶液粘度会增加，而冻融速率会影响这些改变状态的持续时间。冰的形成还会捕获微小的气泡，这可能会进一步破坏蛋白质结构并降低其稳定性。另一个关键因素是冰-液界面的形成。吸附在这些界面上的蛋白质可能会发生结构变化或变性；因此，控制冷却速率至关重要。快速冷冻通常会产生更小的冰晶，并形成更大的冰液界面。这有助于限制缓冲成分的非预期结晶，并有助于维持溶液的pH值。
What does this mean when freezing biologics during manufacturing?在生产过程中冷冻生物制剂意味着什么？Ultimately, freezing is not just a matter of lowering the temperature. For example, fast freezing is optimal for most proteins, such as monoclonal antibodies, whereas slower freezing rates are preferable for other proteins.
6归根结底，冷冻不仅仅是降低温度的问题。例如，快速冷冻对大多数蛋白质（如单克隆抗体）来说是好选择，而较慢的冷冻速率则更适合其他蛋白质。
Precise control over process parameters is required to minimize destabilizing effects and preserve the integrity of biologics. Manufacturers must account for these physical changes and their impact on protein stability to ensure consistent product quality and reliable handling of bulk drug substances.
精确控制工艺参数对于减少不稳定因素并保持生物制剂的完整性至关重要。生产商必须考虑这些物理变化及其对蛋白质稳定性的影响，以确保产品质量的一致性和原料药处理的可靠性。
Figure 5: RoSS® shel l is a protective secondary packaging for all two-dimensional single-use bags currently on the market
图 5：RoSS® shell 是一种适用于目前市面上所有一次性2D袋子的保护性二级包装。
Best practice: Controlled freezing of biologicsThe freezing process has profound implications for the stability of protein-based biologics. Cryoconcentration and the formation of ice-liquid interfaces can lead to the loss of protein structure and function if not properly controlled. The extent of these effects depends on a variety of factors, including:
冷冻过程对蛋白质生物制剂的稳定性有着深远的影响。如果控制不当，冷冻浓缩和冰液界面的形成会导致蛋白质结构和功能的丧失。这些影响的程度取决于多种因素，包括：
Therefore, effective management of these physical changes requires controlled freezing strategies for different container types, such as single-use bags and bottles, and for a range of processing volumes.
因此，要有效管理这些物理变化，需要针对不同类型的容器（如一次性袋子和瓶子）以及不同的加工量制定受控的冷冻策略。
Freezing biologics in single-use bags 将生物制剂冷冻于一次性袋子中2D bioprocess containers that have a small water column can be frozen using plate-freezing technology, which enables more rapid, controlled freezing than traditional static freezing. When employing plate-freezing technology with single-use bags, the bags should be placed in specialized secondary packaging designed to ensure optimal heat transfer. Rapid, controlled freezing using plate freezers enables simultaneous freezing of the drug substance in single-use bags from both the top and the bottom. This helps prevent cryoconcentration of the drug substances and other formulation components in the center of the bag. Both conductive cooling, which provides direct contact with the cooling medium as in plate freezers, and convective cooling, which uses an airflow-based technology as in blast freezers, achieve faster and more homogeneous freezing than static freezers. Figure 6 illustrates the difference in freezing results between static freezers and plate freezers. The degree of cryoconcentration in a single-use bag compared to the initial liquid-state concentration when frozen in a static freezer is significantly higher than that observed when plate-freezing is used. A study conducted in collaboration with Zurich University of Applied Sciences measured cryoconcentration levels of up to +212 % after freezing in a static freezer, whereas cryoconcentration levels using plate freezers showed no major changes.
7对于含有少量水柱的二维生物工艺容器，可采用平板冷冻技术进行冷冻，该技术比传统的静态冷冻技术能够实现更快速、更可控的冷冻。当使用平板冷冻技术处理一次性袋子时，应将袋子置于专门设计的二级包装中，以确保最佳的热传递。平板冷冻机能够从顶部和底部同时冷冻一次性袋子中的药物，从而实现快速、可控的冷冻。这有助于防止药物和其他制剂成分在袋子中心发生冷冻浓缩。无论是传导冷却（如平板冷冻机中与冷却介质直接接触）还是对流冷却（如速冻机中利用气流技术），都能比静态冷冻机实现更快、更均匀的冷冻。图 6 展示了静态冷冻机和平板冷冻机冷冻结果的差异。与静态冷冻机相比，使用平板冷冻技术冷冻的一次性袋子中的冷冻浓缩程度明显更高。与苏黎世应用科学大学合作进行的一项研究测量了静态冷冻机冷冻后的冷冻浓缩水平高达 +212 %，而使用平板冷冻机的冷冻浓缩水平则没有出现重大变化。
Figure 6: Visualized cryoconcentration of uncontrolled conventional freezing (top) vs controlled plate-freezing (bottom)
图 6：非受控常规冷冻（上图）与受控平板冷冻（下图）的冷冻浓缩可视化图
Dark blue spots indicate greater cryoconcentration. Rapid and controlled freezing with a plate freezer enables more homogeneous freezing than conventional freezing.
深蓝色斑点表示冷冻浓缩程度更高。与传统冷冻方法相比，使用平板冷冻机进行快速可控冷冻能够实现更均匀的冷冻效果。
As noted earlier, small air bubbles can occur during the cooling process, which can further affect proteins and reduce their stability. Stress at the liquid-ice interface during the formation of ice can also destabilize proteins.8 So how can these effects be prevented to achieve a homogeneous freezing result? Single Use Support has performed computed tomography (CT) scans to visualize when these phenomena occur to identify ways in which they can be avoided. In Figure 7, an uneven freezing result following static freezing is clearly visible. Bubbles and cracks at the final point of solidification are visible, indicating cryoconcentration.
如前所述，冷却过程中可能会产生微小气泡，这会进一步影响蛋白质并降低其稳定性。冰形成过程中液态-冰界面处的应力也会破坏蛋白质的稳定性。8 那么，如何避免这些影响以获得均匀的冷冻效果呢？Single Use Support 公司进行了计算机断层扫描 (CT)，以观察这些现象发生的时间，并找出避免它们的方法。图 7 清晰地显示了静态冷冻后冷冻效果不均匀的情况。在最终凝固点处可以看到气泡和裂纹，表明存在低温浓缩现象。
Figure 7: CT scan cross-sectional views (horizontal and vertical) of a single-use bag frozen in a static freezer show uneven freezing, with bubbles and cracks concentrated at the final point of solidification
图 7：在静态冰箱中冷冻的一次性袋子的 CT 扫描横截面视图（水平和垂直）显示冷冻不均匀，气泡和裂纹集中在最终凝固点。
Figure 8: CT scan cross-sectional views (horizontal and vertical) of a single-use bag frozen using a plate freezer show homogeneous ice fronts with no bubbles or cracks
图 8：使用平板冷冻机冷冻的一次性袋子的 CT 扫描横截面视图（水平和垂直）显示均匀的冰层前沿，没有气泡或裂纹。
In contrast, Figure 8 shows homogeneous freezing, achieved by following freezing protocols to obtain optimal freezing rates and gradients, using Single Use Support’s plate freezer, RoSS. pFTU. This fully automated, protocol-driven approach not only aligns with US Food and Drug Administration 21 CFR Part 11 standards for electronic records and delivers consistent results across a variety of scales but also maximizes product integrity. The controlled-rate plate freezer RoSS.pFTU, used in combination with Single Use Support’s protective secondary packaging RoSS
® shell, can achieve maximum product quality during the freezing of biologics.
相比之下，图8展示了使用Single Use Support公司的 RoSS.pFTU平板冷冻机，通过遵循冷冻方案获得冷冻速率和梯度，从而实现均匀冷冻。这种全自动、配方驱动的方法不仅符合 (FDA) 21 CFR Part 11 的电子记录标准，并且在各种规模下都能提供一致的结果，而且还能保证产品的完整性。RoSS.pFTU 可控速率平板冷冻机与 Single Use Support 公司的 RoSS
® 保护性二级包装外壳配合使用，可在生物制品冷冻过程中实现产品质量。
The RoSS® shell offers robust, reliable, and secure protection for single-use bioprocess containers of any size and vendor during freezing, transportation, storage, and thawing.
RoSS® 外壳为任何尺寸和供应商的一次性生物工艺容器在冷冻、运输、储存和解冻过程中提供强大、可靠和安全的保护。
With its innovative design, the RoSS
® shell is a tamper-evident system that minimizes contamination risk and ensures all single-use bags are efficiently cooled using plate freezing technology while providing protection during storage and shipping. This:
凭借其创新设计，RoSS® 外壳是一个防篡改系统，可降低污染风险，并确保所有一次性袋子均能使用平板冷冻技术进行高效冷却，同时在储存和运输过程中提供保护。
Minimizes product losses attributable to bag breakages
减少因袋子破损造成的产品损失
Maximizes product quality by providing optimal freezing and thawing conditions
通过提供冷冻和解冻条件，提高产品质量
Is compatible with all types of two-dimensional (2D) single-use bags
兼容所有类型的二维（2D）一次性袋子
Single-use bags secured within the robust RoSS
® shell can be placed into the
RoSS.pFTU plate-based freezer, which:
一次性袋子固定在坚固的 RoSS® 外壳内，可放入 RoSS.pFTU 平板式冷冻机中，该冷冻机：
Enables controlled freezing down to -80 °C with the highest possible speed and accuracy
能够以高速度和精度实现低至-80°C的受控冷冻
Offers a capacity of up to 400 L, depending on bag type
容量高达400升，具体取决于袋子类型
Is fully compatible with 2D single-use bags of any size and from any vendor
兼容任何尺寸、任何供应商的二维一次性袋子
Can achieve optimal product stability results for bulk drug substances, including monoclonal antibodies
可实现原料药（包括单克隆抗体）的产品稳定性
Is fully automated and ready for cGMP use
全自动运行，符合cGMP要求
Figure 9: Fully loaded RoSS.pFTU Large Scale
图 9：满载的 RoSS.pFTU 大规模
Freezing biologics in bottles 将生物制剂冷冻于瓶中Unlike single-use bags, bottles present unique challenges when used to freeze biologics; this is due to their bulk and their requirement for vertical placement during freezing. It is therefore recommended to freeze bottles using static or blast freezing methods.
与一次性袋子不同，瓶子在冷冻生物制剂时面临着独特的挑战；这是由于瓶子体积较大，且冷冻过程中需要垂直放置。因此，建议采用静态冷冻或速冻方法冷冻瓶子。
However, uncontrolled freezing in bottles often leads to uneven temperature gradients and cryoconcentration, compromising product quality. Blast freezing, particularly with forced air flow, is superior to static freezing methods but still requires careful control.
然而，瓶内冷冻若不受控制，往往会导致温度梯度不均匀和浓缩，从而影响产品质量。速冻，特别是采用强制气流的速冻，优于静态冷冻方法，但仍需严格控制。
Studies have shown that uncontrolled freezing can result in considerable differences in solute concentration between the top and bottom of a bottle, indicating heterogeneous freezing and reduced reproducibility, with cryoconcentration levels increasing by more than 300 %.
9研究表明，冷冻若不受控制，会导致瓶内顶部和底部溶质浓度出现显著差异，表明冷冻不均匀，重复性降低，浓缩程度增加超过300%。
As a bottle is subjected to the freezing process, pressure on the side walls from the growing ice fronts pushes liquid toward the center, forming a cone at the top. This phenomenon is known as the “volcano effect", illustrated in Figure 10.
当瓶子处于冷冻过程中时，不断增长的冰锋对瓶壁施加压力，将液体推向中心，在顶部形成锥形。这种现象被称为“火山效应"，如图10所示。
Figure 10: Visualized cryoconcentration in bottles under uncontrolled freezing conditions showing the “volcano effect" (left) compared with controlled blast freezing (right)
图 10：在不受控制的冷冻条件下，瓶中低温浓缩的可视化结果，显示了“火山效应"（左图），并与受控的速冻（右图）进行了比较。
To address these issues, Single Use Support has developed controlled-rate freezing protocols for bottles. For large bottles, freezing rates of approximately -0.1 °C to -0.5 °C/min are essential for maintaining protein stability.4,10 Controlled air distribution with advanced air flow systems optimizes the freezing behavior of drug substances to ensure bottle-to-bottle reproducibility and homogeneous freezing results. Visualization of heat transfer and airflow patterns demonstrates that high-performance forced air distribution enables consistent temperature control and uniform freezing. Single Use Support’s
RoSS.BLST is a blast freezer that controls the rate of cooling by employing smart air distribution, as shown in Figure 11. It is a modular, controlled-rate blast freezer that incorporates forced-air technology. Its best-in-class chamber size-to-foot-print ratio enables manufacturers to efficiently freeze bulk-packaged biologics. It can accommodate bottles, bulky single-use bag setups, and other single-use containers. For example, it can accommodate up to 192 2 L bottles and can freeze drug substances according to optimal freezing protocols to achieve maximum product stability. It also contributes to efficient and sustainable freezing by providing great process flexibility:
为了解决这些问题，Single Use Support 开发了适用于瓶装产品的控温速冻方案。对于大瓶装产品，约 -0.1℃ 至 -0.5 °C/min 的速冻速率对于维持蛋白质稳定性至关重要
4,10。采用气流系统的可控空气分配能够优化药物的冷冻行为，确保瓶与瓶之间冷冻效果的可重复性和均匀性。热传递和气流模式的可视化结果表明，高性能强制空气分配能够实现稳定的温度控制和均匀的冷冻效果。如图 11 所示，Single Use Support 的 RoSS.BLST 是一款采用智能空气分配控制冷却速率的速冻机。它是一款模块化、控温速冻机，并采用了强制空气技术。其腔室尺寸与占地面积比使生产商能够高效地冷冻散装生物制剂。它可以容纳瓶装产品、体积较大的一次性袋子以及其他一次性容器。例如，它最多可容纳 192 瓶 2 升装药品，并可根据冷冻方案冷冻药品，以实现产品稳定性。此外，它还具有高的工艺灵活性，有助于实现高效且可持续的冷冻：
Modular shelving for bottle sizes ranging from 30 mL to 10 L
模块化货架，适用于30毫升至10升的瓶装饮料
Sustainable design with natural refrigerants and a low refrigerant load
采用可持续设计，使用天然制冷剂，制冷剂负荷低
Complies with EN 378 and ISO 5149 standards
符合EN 378和ISO 5149标准
Includes thawing functionality with integrated shaking
内置摇晃功能，可解冻饮料
Figure 11: Visualization of heat transfer and airflow patterns when using RoSS.BLST for temperature control , showing the high-performance forced air distribution when used with single-use bottles (top) and bags (bottom)
图 11：使用 RoSS.BLST 进行温度控制时的热传递和气流模式可视化，显示了与一次性瓶子（上图）和袋子（下图）一起使用时的高性能强制空气分配。
Bottle RoSS protects bottle caps with attached tubing assemblies. It provides tamper-evident integrity and reduces product losses during cold chain storage and shipping. Therefore, Bottle RoSS ensures the safe, efficient, and scalable management of biologics in bottles, regardless of bottle manufacturer or type.
Bottle RoSS 通过连接的管路组件保护瓶盖。它提供防篡改保护，并减少冷链储存和运输过程中的产品损失。因此，无论瓶子制造商或类型如何，Bottle RoSS 都能确保对瓶装生物制剂进行安全、高效且可扩展的管理。
Figure 12: A RoSS.BLST fully loaded with 2 L bottles 图 12：装满 2 升瓶子的 RoSS.BLST
Figure 13: Bottle RoSS for protection of single-use assemblies on bottles during cold chain handling
图 13：瓶身 RoSS，用于在冷链搬运过程中保护瓶子上的一次性组件。
Maintaining cold chain for storage and transport维持冷链以进行储存和运输The efficient and safe freezing of biologics in single-use bags and bottles requires a fully closed, Annex 1-aligned, and aseptic system during the entire fluid and cold chain management process. The process begins with automated filling and filtration, continues through freezing, cold storage and shipping, and concludes with controlled thawing at the drug product site, until the drug substance is removed from the singleuse containers for fill/finish. The integration of closed systems at every stage minimizes contamination risks, streamlines workflows, and ensures product integrity. This end-toend strategy fosters compatibility between single-use technologies, regardless of the type or size of primary packaging used by the manufacturer. Furthermore, closed systems fulfill GMP-relevant standards, and can be seamlessly integrated into customer networks for process control. An automated and compatible cold chain improves operational efficiency, making it the gold standard for the management of single-use containers used in biopharmaceutical manufacturing, such as single-use bags and bottles.
生物制剂在一次性袋子和瓶中的高效安全冷冻，需要在整个液体和冷链管理过程中采用封闭、符合附件1要求且无菌的系统。该流程始于自动化灌装和过滤，贯穿冷冻、冷藏和运输，最终在药品生产现场进行受控解冻，直至将原料药从一次性容器中取出进行灌装/包装。在每个阶段集成封闭系统可限度地降低污染风险，简化工作流程，并确保产品完整性。这种端到端策略促进了各种一次性技术之间的兼容性，无论制造商使用何种类型或尺寸的初级包装。此外，封闭系统符合GMP相关标准，并且可以无缝集成到客户网络中进行过程控制。自动化且兼容的冷链提高了运营效率，使其成为生物制药生产中一次性容器（例如一次性袋子和瓶）管理的黄金标准。
Cold storage of biologics 生物制剂的冷藏For ultra-low temperature storage, the
RoSS.ULTF platform provides secure, scalable cold storage down to -80 °C. The modul ar interior can accommodate either single-use bags protected in RoSS® shells or single-use bottles and their assemblies protected with Bottle RoSS, as well as other bulk-packaged drug substances of various sizes and batch volumes. This design ensures compatibility with all container types and safety for high-value drug substances. Automated monitoring and GMP-compatible documentation support regulatory requirements and batch traceability.
RoSS.ULTF平台专为超低温储存而设计，可提供安全、可扩展的冷藏环境，温度可达-80°C。其模块化内部结构可容纳RoSS®外壳保护的一次性袋子、RoSS®瓶装保护的一次性药瓶及其组件，以及其他各种规格和批次的散装药品。该设计确保与所有容器类型兼容，并保障高价值药品的安全性。自动化监控和符合GMP规范的文档记录功能可满足监管要求和批次追溯性。
Cold chain shipping container 冷链运输集装箱Maintaining cold chain is critical when transporting bulk drug substances. The
RoSS.SHIP solution enables safe, temperature-controlled shipping of bottles and bags. This container is specifically designed to maintain cold chain, ensuring that bulk drug substances remain at temperatures below -60°C for several days during transport. Integrated track and trace technology enables real-time monitoring of temperature and location, providing full visibility and compliance throughout transit. RoSS.SHIP’s robust packaging minimizes the risk of breakage, contamination, and product loss, ensuring that biologics arrive at their destination in optimal condition.
在运输原料药时，维持冷链至关重要。RoSS.SHIP解决方案可实现瓶装和袋装原料药的安全温控运输。该容器专为维持冷链而设计，确保原料药在运输过程中数日内保持在-60°C以下的温度。集成的追踪溯源技术可实时监控温度和位置，从而在整个运输过程中提供全面的可视性和合规性。RoSS.SHIP坚固的包装限度地降低了破损、污染和产品损失的风险，确保生物制剂以好状态抵达目的地。
Figure 14: Ultra-cold storage of biologics with RoSS.ULTF
图 14：采用 RoSS.ULTF 进行生物制剂的超低温储存
Figure 15: The cold chain shipping container RoSS.SHIP
图 15：冷链运输集装箱 RoSS.SHIP
Thawing biologics at the drug product site 在药品生产现场解冻生物制剂 
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