生物制剂的冷冻和冷链解决方案——最佳实践

Freezing and cold chain solutions for biologics – best practices
生物制剂的冷冻和冷链解决方案——优秀实践
Alexander Fuchs
May 6, 2024
 
Freezing biologics is an almost unavoidable step in the process of preserving and storing them for an extended period of time. After all, biologics encompass a diverse range of therapeutic products derived from living organisms. They include monoclonal antibodies, protein solutions, and other biotherapeutics – complex formulations engineered to treat various diseases and medical conditions. The freeze-thaw process requires close attention to formulation, cooling rates, and cryoprotective strategies to maintain the stability and efficacy of the drug product.
冷冻是生物制剂长期保存和储存过程中几乎不可避免的步骤。毕竟，生物制剂涵盖了多种源自活体生物的治疗产品，包括单克隆抗体、蛋白质溶液和其他生物治疗药物——这些复杂的制剂旨在治疗各种疾病和病症。冻融过程需要密切关注制剂配方、冷却速率和冷冻保护策略，以维持药物产品的稳定性和疗效。
Safe cold storage of biologics is key in ensuring the efficacy and safety of pharmaceutical products throughout their lifecycle. As the demand for biopharmaceuticals continues to rise, so does the need for efficient and reliable storage solutions that maintain the integrity of the cold chain. Biologics are often highly temperature-sensitive, requiring precise control to prevent degradation and ensure potency.
生物制剂的安全冷藏是确保药物产品在其整个生命周期内疗效和安全性的关键。随着对生物制药的需求持续增长，对能够维持冷链完整性的高效可靠储存解决方案的需求也日益增加。生物制剂通常对温度高度敏感，需要精确控制温度以防止降解并确保其效力。
In this article, we will discuss essential requirements and innovative solutions for freezing and storing biologics along the cold chain – from ultracold and cryogenic freezers to solutions for safe packaging of biologics.

本文将探讨生物制剂在冷链中冷冻和储存的基本要求和创新解决方案——从超低温和低温冷冻机到生物制剂的安全包装方案。
 
Biologics early considerations 生物制剂早期考量
Freezing biologics demands the consideration of various critical factors to uphold their integrity and efficacy throughout the process. Some of these considerations include:
生物制剂的冷冻保存需要考虑多种关键因素，以确保其在整个过程中保持完整性和有效性。这些因素包括：
Container selection: Vials, cryovessels, or single-use bags – there are numerous types of containers to choose from when freezing biologics. It is important for manufacturers to consider the thermodynamic characteristics of the materials they are made of to ensure that they can endure the stress that may come with extreme temperature gradients while protecting valuable therapies, such as mAbs or mRNA vaccines.
容器选择：冷冻保存生物制剂时，可选择的容器类型多种多样，例如小瓶、冷冻容器或一次性冷冻袋。生产商必须考虑容器材料的热力学特性，以确保其能够承受温度梯度带来的压力，同时保护重要的治疗药物，例如单克隆抗体或mRNA疫苗。
However, container options do not only differ in terms of built materials, but also in regard to their size: The volume of individual units significantly impacts their freezing behavior, thus also the risk for detrimental effects of freezing like unwanted ice crystal formation or protein concentration.
然而，容器的选择不仅体现在材料上，还体现在其尺寸上：单个容器的体积会显著影响其冷冻性能，进而影响冷冻过程中可能产生的有害影响，例如形成不必要的冰晶或蛋白质浓缩。
Formulation and cryoprotective agents: Biologics themselves are already highly complex structures, but they are often not frozen alone, but in combination with other substances, such as cryoprotective agents (CPAs or cryoprotectants). Excipients like glycerol and glycol in formulation development play vital roles in mitigating cryoconcentration effects and sustaining the stability of proteins during freezing and thawing cycles.
制剂和冷冻保护剂：生物制剂本身就是高度复杂的结构，但它们通常并非单独冷冻，而是与其他物质（例如冷冻保护剂）混合使用。在制剂研发中，甘油和乙二醇等辅料在减轻冷冻浓缩效应和维持蛋白质在冻融循环中的稳定性方面发挥着至关重要的作用。
Freezing and thawing protocols: Cooling rates are a fundamental aspect in achieving desired freeze-thaw profiles and preserving protein stability. It is one of the most decisive steps in unit operation of pharmaceutical freezers, which is why the next chapter will discuss this facet in more detail. ¹
冻融方案：冷却速率是实现理想冻融曲线和保持蛋白质稳定性的关键因素。它是制药冷冻机单元操作中最关键的步骤之一，因此下一章将更详细地讨论这一方面。
 
Hitting the right cooling rate and speed for biological drug substances
生物药物的冷却速率和速度要合适。
Hitting the optimal cooling rate is crucial when freezing biological drug substances. This rate directly impacts various aspects of the process, including ice formation, protein denaturation, and overall product stability.
在冷冻生物药物时，达到冷却速率至关重要。该速率直接影响工艺的各个方面，包括冰的形成、蛋白质变性和产品的整体稳定性。
Since there is no cooling and thawing rate that is considered to be universally ideal, it has to be individualized for each product. This requires thorough stability studies, including characterization of all its components and the kinetics occurring during freezing.
由于不存在普遍适用的理想冷却和解冻速率，因此必须针对每种产品进行个性化设置。这需要进行全面的稳定性研究，包括对所有成分的表征以及冷冻过程中发生的动力学变化。
Linked to freezing rates is the time for phase transition as an even more crucial factor for protein stability: It refers to the amount of time it takes for the product to transition from the liquid to the frozen state, and determines effects like cryoconcentration, pH changes, and glass formation. ²
与冷冻速率密切相关的是相变时间，它是影响蛋白质稳定性的一个更为关键的因素：相变时间是指产品从液态转变为固态所需的时间，它决定了诸如冷冻浓缩、pH 值变化和玻璃态形成等效应。
 
Freezing strategies for biologics 生物制剂的冷冻策略
Biotechnology knows several freezing strategies for biologics, with some of them being more eligible than others. However, it always depends on the very scope that a pharmaceutical company or CDMO has when subjecting their products to a distinct freezing method, as well as the individual product characteristics.
生物技术领域针对生物制剂开发了多种冷冻策略，其中一些策略比其他策略更适用。然而，最终选择哪种冷冻方法，始终取决于制药公司或合同研发生产机构（CDMO）的具体业务范围以及产品的特性。
In the following sections, we will discuss four methods to freeze biologics and biosimilars.
在接下来的章节中，我们将讨论四种生物制剂和生物类似药的冷冻方法。
 
Slow uncontrolled freezing 缓慢不受控制的冷冻
Slow uncontrolled freezing, characterized by gradual cooling rates and minimal control over ice crystal formation, may appear as a simple approach, but poses significant risks to protein solutions. This method often results in the formation of unwanted ice crystals, inducing denaturation and compromising product stability.
缓慢且不受控的冷冻方法，其特点是冷却速率缓慢，且对冰晶形成控制甚微，看似简单，但却对蛋白质溶液构成重大风险。该方法通常会导致形成不必要的冰晶，从而诱发蛋白质变性并损害产品稳定性。
Furthermore, slow freezing brings an increased risk for cryoconcentration, describing an inhomogeneous distribution of protein mass within the sample. ³
此外，缓慢冷冻还会增加冷冻浓缩的风险，冷冻浓缩是指样品中蛋白质质量分布不均匀。³
 
 Lyophilization of biologics 生物制剂的冻干
Lyophilization, or freeze-drying, stands as a popular method for preserving biologics, involving freezing the product followed by ice removal under vacuum for extended frozen storage. This process utilizes buffer solutions like sucrose to minimize ice nucleation and stabilize protein formulations.
冻干，也称冷冻干燥，是一种常用的生物制剂保存方法，其原理是将产品冷冻，然后在真空条件下去除冰层，从而实现长期冷冻保存。该过程利用蔗糖等缓冲溶液来减少冰核的形成并稳定蛋白质制剂。
While lyophilization offers advantages in the preservation of biopharmaceuticals, it also presents disadvantages. These may include high operational costs, longer processing times, and product loss as a result of protein denaturation. Therefore, products like pharmaceuticals based on LNPs are usually not freeze-dried. ⁴
虽然冻干在生物制药的保存方面具有优势，但也存在一些缺点。这些缺点包括较高的操作成本、较长的处理时间以及因蛋白质变性造成的产品损失。因此，像基于脂质纳米颗粒（LNP）的药物这类产品通常不采用冻干工艺。
 
Controlled plate freezing 受控平板冷冻
Controlled plate freezing is a methodical approach to freezing biologics that involves precise regulation of freezing rates and temperature gradients. This technique is not only valuable during process development and small-scale production: With innovative plate freezing and thawing systems like RoSS.pFTU, both small and large-scale freezing of biologics is possible.
可控平板冷冻是一种系统化的生物制剂冷冻方法，它涉及对冷冻速率和温度梯度的精确控制。这项技术不仅在工艺开发和小规模生产中具有价值，而且借助RoSS.pFTU等创新型平板冷冻和解冻系统，生物制剂的小规模和大规模冷冻均可实现。
By optimizing heat transfer and freezing time, controlled plate freezing ensures the preservation of protein stability throughout the freezing process, with a decreased risk for protein aggregation and other unwanted freezing effects.
通过优化传热和冷冻时间，可控平板冷冻能够确保蛋白质在整个冷冻过程中保持稳定性，并降低蛋白质聚集和其他不良冷冻效应的风险。

Freeze & Thaw platform 冷冻和解冻平台 The Single Use Support freeze-thaw platforms provide insular solutions for the freeze/thaw processes of each clinical phase. Our new freeze-thaw units are fully scalable and compatible with all batch sizes and bags from all established manufacturers – you will only require one single system from the lab to blockbuster production. 一次性使用的冻融平台为每个临床阶段的冻融流程提供独立的解决方案。我们全新的冻融装置具有可扩展性，并兼容所有制造商的所有批次规格和包装袋——您只需一套系统即可完成从实验室到重磅药物生产的整个流程。

 
 
Cryogenic freezing and cryopreservation 低温冷冻和冷冻保存
Cryogenic freezing involves the use of extremely low temperatures (down to around -180°C) for the preservation of biologics, ensuring long-term stability and viability. This method, integral to cryopreservation, safeguards the integrity of biotherapeutics over extended periods.
低温冷冻是指利用极低温度（低至约-180°C）保存生物制品，以确保其长期稳定性和活性。该方法是冷冻保存不可少的一部分，能够长期保障生物治疗药物的完整性。
Cryobiology plays an important role in individualizing the ideal process parameters and storage temperatures for, e.g., cell therapies, which are typically stored at around -150°C. It represents an essential preservation method in bioprocessing, when ultra-low temperatures (around -80°C) are not sufficient to preserve product quality.
低温生物学在确定理想的工艺参数和储存温度方面发挥着重要作用，例如，细胞疗法通常储存在约-150°C的温度下。当超低温（约-80°C）不足以保证产品质量时，低温冷冻便成为生物加工过程中不可少的保存方法。
Control over freezing rates, though, has long been a major challenge during cryogenic freezing, due to the use of liquid nitrogen as cooling means. Single Use Support has therefore developed the first truly controlled cryogenic freezer, the RoSS.LN2F, which protects biologics from full exposure to LN2 while following adjustable freezing profiles. ⁵
然而，由于使用液氮作为冷却手段，控制冷冻速率一直是低温冷冻过程中的一大挑战。因此，Single Use Support公司开发了真正可控的低温冷冻机RoSS.LN2F，该设备能够根据可调节的冷冻曲线，在避免生物制品暴露于液氮的情况下，保护其免受液氮的直接影响。

RoSS.LN2F | Cryogenic Freezer低温冷冻机 RoSS.LN2F is a powerful cryogenic controlled rate freezer for temperatures down to -170°C. An enclosed LN2 system and our innovative direct injection system ensure no direct exposure and no mechanical compressors are needed. This ensures a safe, low-maintenance and energy-saving handling. RoSS.LN2F 是一款功能强大的低温可控速冷冻机，可实现低至 -170°C 的温度。其封闭式液氮系统和我们创新的直接喷射系统确保了无直接接触，无需机械压缩机。这保证了安全、低维护和节能的操作。

 
Freezing biologics and the advances with single-use technologies
生物制剂的冷冻保存及一次性使用技术的进步
For cryopreservation of sensitive biologics Single Use Support is convinced of plate freezing and cryogenic freezing as two extremely favorable approaches to control the cooling and thawing process. They can ideally cater to individual product requirements in terms of cooling rates and target temperature, ensuring ideal results upon thawing.
对于敏感生物制剂的冷冻保存，Single Use Support 坚信平板冷冻和低温冷冻是控制冷却和解冻过程的两种极其理想的方法。它们能够很好满足不同产品在冷却速率和目标温度方面的个性化需求，确保解冻后达到理想效果。
This is why Single Use Support offers innovative solutions for both methods, providing reliable and scalable options for controlled freezing and thawing. The plate-based freeze and thaw technology of the RoSS.pFTU platform ensures homogeneous processing with full control over the process, minimizing the formation of ice crystals and maintaining the stability of biologic substances.
因此，Single Use Support 为这两种方法提供了创新解决方案，为可控的冷冻和解冻提供了可靠且可扩展的选择。RoSS.pFTU 平台的平板式冻融技术可确保处理过程的均匀性，并实现对整个过程的控制，大限度地减少冰晶的形成，从而维持生物物质的稳定性。
The cryogenic freezer RoSS.LN2F, on the other hand, enables pharmaceutical manufacturers to ensure long-term storage at even lower temperatures, ensuring the viability of biotherapeutics like certain cell-based products – for small and large volumes.
另一方面，低温冷冻机 RoSS.LN2F 使制药企业能够在更低的温度下进行长期储存，从而确保某些细胞疗法等生物治疗药物（无论小批量还是大批量）的活性。
Both systems work with high-quality single-use bags covered in the RoSS® Shell as protective packaging solution. And being based on a modular and vendor-agnostic setup, the solutions by Single Use Support are fully scalable, catering to both small and large scale demands when processing bulk drug substances.
这两个系统均采用高品质的一次性包装袋，并以 RoSS® Shell 作为保护性包装解决方案。 Single Use Support 的解决方案基于模块化和供应商无关的架构，具有可扩展性，能够满足原料药加工过程中从小规模到大规模的各种需求。
Single Use Support couples the individual strengths of plate and cryogenic freezing with the overall advantages of single-use technologies: They allow for safe and efficient bioprocessing, with elevated flexibility, cost-effectiveness, and sustainability due to a reduction of resource consumption for manual cleaning and sterilization.
Single Use Support 将平板冷冻和低温冷冻各自的优势与一次性技术的整体优势相结合：由于减少了人工清洁和灭菌所需的资源消耗，该方案能够实现安全高效的生物加工，并具有更高的灵活性、成本效益和可持续性。
 
 
What’s needed along the cold chain of biologics?
生物制剂冷链需要哪些环节？
The safe storage of biologics along the cold chain requires meticulous attention to several critical factors to ensure product integrity and efficacy. From temperature control to protection from contamination, various elements must be carefully managed to maintain the quality of biologic products throughout biomanufacturing – all in regard to regulatory compliance.
生物制剂在冷链中的安全储存需要对多个关键因素进行细致关注，以确保产品的完整性和有效性。从温度控制到防止污染，必须精心管理各种要素，以在整个生物制药过程中维持生物制品的质量——所有这些都必须符合监管要求。
What makes cold chain management of biologics and biosimilars even more complex is the need for individualized approaches, depending on the very product or intermediate that is currently being processed. Different types of biologics have unique requirements and vulnerabilities – e.g. physical stress, light or oxygen exposure. One of the most common aspects to be considered is temperature, along with bringing efficiency and safety into harmony.
生物制剂和生物类似药的冷链管理之所以更加复杂，是因为需要根据当前正在加工的具体产品或中间体采取个性化的方法。不同类型的生物制剂具有独特的要求和脆弱性——例如，物理应力、光照或氧气暴露。需要考虑的常见因素之一是温度，以及如何在效率和安全性之间取得平衡。
Best choice for cold storage of Biopharmaceuticals - A Comparison
生物制药冷藏的优秀选择——比较
 
 
Temperature control in cold storage 冷库的温度控制
Temperature control plays a pivotal role in the storage of biologics due to the inherent sensitivity of these products to temperature fluctuations. Biologics, such as mRNA vaccines or allogeneic stem cell therapies, often contain delicate molecular structures that can be easily compromised by exposure to inappropriate temperatures.
由于生物制品本身对温度波动非常敏感，温度控制在生物制品的储存中起着至关重要的作用。例如，mRNA疫苗或异体干细胞疗法等生物制品通常含有精细的分子结构，暴露于不适宜的温度下很容易受到破坏。
Maintaining the prescribed temperature range is critical to preserving the stability and efficacy of biologic products. Deviations from the recommended storage conditions can lead to irreversible damage, including denaturation of proteins, loss of biological activity, protein stability, and degradation of nucleic acids. These alterations can not only render the product ineffective, but also pose potential safety risks to patients.
维持规定的温度范围对于保持生物制品的稳定性和有效性至关重要。偏离推荐的储存条件会导致不可逆的损害，包括蛋白质变性、生物活性丧失、蛋白质稳定性下降以及核酸降解。这些改变不仅会使产品失效，还会对患者构成潜在的安全风险。
It is the recommended storage temperature that, being specific for each product type, makes cold chain management so complex for pharmaceutical companies and CDMOs. For instance, Fc-fusion proteins have been found to aggregate during long-term storage at -30°C; samples stored at both -70°C and -20°C, on the other hand, remained stable.
正是由于每种产品类型的推荐储存温度各不相同，才使得制药公司和合同研发生产机构（CDMO）的冷链管理如此复杂。例如，研究发现Fc融合蛋白在-30°C长期储存期间会发生聚集；而储存在-70°C和-20°C的样品则保持稳定。
Nevertheless, there are some rules of thumb regarding typical storage temperatures for biologics:
不过，关于生物制剂的典型储存温度，有一些经验法则：

• monoclonal antibodies: -80°C单克隆抗体：-80°C

• mRNA: -80°C 

• gene therapies: -80°C 基因疗法：-80°C

• cell therapies: -130°C and lower 细胞疗法：-130°C 及以下

• gene-modified cell therapies: lower than -150°C 基因修饰细胞疗法：低于 -150°C

Furthermore, the temperature sensitivity of biologics extends beyond storage to transportation and handling. Fluctuations in temperature during transit can have detrimental effects on product quality, particularly if the excursion occurs outside the acceptable range.
此外，生物制品的温度敏感性不限于储存，还体现在运输和处理过程中。运输过程中的温度波动会对产品质量产生不利影响，尤其是在温度波动超出可接受范围的情况下。
 
Combining efficiency and safety 兼顾效率与安全性
Achieving the delicate equilibrium between efficiency and safety is a balancing act in the storage of biologics. While optimizing storage processes for efficiency is essential to meet production demands and minimize costs, it must not compromise the safety and integrity of biologic products.
在生物制品的储存过程中，如何在效率和安全性之间取得微妙的平衡至关重要。优化储存流程以提高效率对于满足生产需求和降低成本至关重要，但绝不能以牺牲生物制品的安全性和完整性为代价。
Efficiency in storage entails streamlining workflows, maximizing storage capacity, and minimizing downtime. However, these optimizations must not compromise safety measures, such as temperature control, contamination prevention, and product traceability.
提高储存效率意味着简化工作流程、大容量存储容量和最小化停机时间。然而，这些优化措施绝不能影响安全措施，例如温度控制、污染预防和产品可追溯性。
By integrating efficient storage practices with advanced systems and robust safety protocols, biopharmaceutical companies can ensure that biologic products are stored in optimal conditions while reducing the risk of product loss or compromise. This holistic approach to storage management not only optimizes efficiency in biomanufacturing, but also safeguards product quality and patient safety throughout the cold chain. ^6 7
通过将高效的储存实践与优秀的系统和完善的安全规程相结合，生物制药公司可以确保生物制品在条件下储存，同时降低产品损失或受损的风险。这种全面的储存管理方法不仅优化了生物制药的效率，而且在整个冷链过程中保障了产品质量和患者安全。
 
窗体底端
Managing the cold chain: The potential of single-use technologies
冷链管理：一次性技术的潜力
Effectively managing the cold chain presents significant challenges in the storage and transportation of biologics or biosimilars. However, single-use technologies offer immense potential in addressing these challenges and optimizing cold chain management processes.
有效管理生物制剂或生物类似药的冷链在储存和运输方面面临着诸多挑战。然而，一次性技术在应对这些挑战和优化冷链管理流程方面展现出巨大的潜力。
In contrast to walk-in freezers and cold rooms, upright ultra-cold storage freezers with a customized inner shelving system allow maximized storage density and space efficiency. Combined with advanced temperature control including digital alarming management as well as long temperature holding in the case of failure, these freezers offer an elevated level of reliability and safety while being energy-effective and user-friendly.
与步入式冷冻库和冷藏室相比，配备定制内部搁架系统的立式超低温冷冻库能够大限度地提高存储密度和空间利用率。结合优秀的温度控制技术（包括数字报警管理）以及故障时的长时间温度保持功能，这些冷冻库在提供更高可靠性和安全性的同时，还兼具节能和易用性。
As not only the number of individual freezers, but also their interior can be customized according to specific needs, they are prepared to be used at different scales, making production lines ready for future changes in capacity needs.
由于不仅冷冻库的数量，而且其内部结构也可以根据具体需求进行定制，因此它们可以适应不同规模的应用，使生产线能够应对未来产能需求的变化。
 
 
Ultra-cold storage for biologics – when refrigeration is not enough
生物制剂的超低温储存——当普通冷藏不足以满足需求时
Ultra-cold storage involves temperatures around -80°C, and is crucial for preserving the efficacy and stability of biologics, such as vaccines, cell therapies, and mRNA-based drugs. These delicate biopharmaceuticals often require storage at ultra-low temperatures to prevent degradation and maintain protein stability along with therapeutic properties.
超低温储存是指在约-80°C的温度下进行储存，对于保持生物制剂（例如疫苗、细胞疗法和mRNA药物）的疗效和稳定性至关重要。这些敏感的生物制药产品通常需要在超低温下储存，以防止降解并维持蛋白质稳定性及其治疗特性。
Ultra-low temperature storage can either be necessary超低温储存可能是必要的。

• right after freezing for shipping and long term storage,冷冻后立即进行运输和长期储存；

• upon arrival at the drug product manufacturing site prior to fill/finish,

到达药品生产现场后，在灌装/完成之前；

• or when buffer, media or intermediate drug substances need to be short- or midterm stored during bioprocessing.

或者当缓冲液、培养基或中间药物物质在生物加工过程中需要短期或中期储存时。
However, achieving and maintaining such extreme temperatures presents several challenges:
然而，实现并维持如此低的温度面临着诸多挑战：

• Infrastructure requirements: Ultra-cold storage necessitates specialized freezers with precise temperature control capabilities, which can be expensive to purchase and maintain. Additionally, facilities must have adequate space, power supply, and backup systems to support these freezers – and to scale up capacities if need be. Here, storage density is an essential criterion, as e.g. walk-in freezers come with a large footprint, need specialized infrastructure, and require a considerable amount of energy, while upright storage freezers may be more resource effective.

基础设施要求：超低温储存需要具备精确温度控制功能的专用冷冻机，其购置和维护成本可能很高。此外，设施必须拥有足够的空间、电力供应和备用系统来支持这些冷冻机，并在必要时扩展容量。存储密度是关键因素，例如，步入式冷冻库占地面积大，需要专用基础设施，并且需要大量能源，而立式冷冻库可能更节能。

• Temperature control: Maintaining consistent temperatures throughout the storage period is paramount for ensuring the integrity of biologics. Fluctuations or deviations from the desired temperature range can compromise product quality and efficacy, leading to potential safety concerns.

温度控制：在整个储存期间保持温度稳定对于确保生物制品的完整性至关重要。温度波动或偏离所需范围会影响产品质量和疗效，从而导致潜在的安全问题。

• Logistical concerns: Transporting biologics to and from ultra-cold storage facilities requires careful planning and coordination to prevent temperature excursions. Any deviation from the recommended temperature range during transit can result in product degradation and loss of potency.

物流问题：将生物制品运送到超低温储存设施或从超低温储存设施运出需要周密的计划和协调，以防止温度波动。运输过程中任何偏离推荐温度范围的情况都可能导致产品降解和效力降低。
Single Use Support's ultra cold storage RoSS.ULTF addresses these challenges by offering precise temperature control down to -75°C (-103°F), ensuring the integrity of stored biologics. Its modularity allows for tailored shelving systems to accommodate various sizes of bioprocess containers, maximizing storage density and providing efficient storage solutions.
Single Use Support 的超低温存储系统 RoSS.ULTF 通过提供低至 -75°C (-103°F) 的精确温度控制，有效应对了这些挑战，确保储存的生物制品的完整性。其模块化设计允许定制货架系统，以适应各种尺寸的生物工艺容器，从而大限度地提高存储密度并提供高效的存储解决方案。
Moreover, its modularity enables easy integration into existing facilities, offering flexibility in storage location and setup. Being compatible not only with RoSS® Shells as a dedicated protective packaging solution further discussed below, but also with all other primary packagings, the RoSS.ULTF provides additional protection for single-use bioprocess containers during storage and transport.
此外，其模块化设计使其能够轻松集成到现有设施中，从而在存储位置和设置方面提供更大的灵活性。RoSS.ULTF 不仅与下文将详细介绍的专用保护性包装解决方案 RoSS® Shells 兼容，而且与所有其他初级包装兼容，可在存储和运输过程中为一次性生物工艺容器提供额外的保护。

RoSS.ULTF | Ultra-low Temperature Storage 超低温储藏冷冻柜 RoSS.ULTF is an ultra-low temperature storage fridge for frozen drug substances in different sizes. The ULT storage freezer keeps the desired set point temperature down to -80°C. RoSS.ULTF offers highest storage density, is fully movable and can be modularly adapted to your individual needs. RoSS.ULTF 是一款超低温冷冻药品存储冰箱，适用于不同规格的冷冻药品。该超低温存储冰箱可将设定温度维持在 -80°C 以下。RoSS.ULTF ，具有优秀的存储密度，可移动，并可根据您的具体需求进行模块化定制。

 
Enhanced protection during cold storage and logistics of biologics
加强生物制品冷藏和物流过程中的保护
Effective protection during biologic storage is crucial for maintaining potency and safety. Temperature fluctuations and environmental factors can compromise their integrity, leading to reduced efficacy or complete loss. Robust protection measures are thus essential.
在生物制剂储存过程中，有效的保护对于维持其效力和安全性至关重要。温度波动和环境因素会损害其完整性，导致效力降低甚至丧失。因此，强有力的保护措施不可少。
The RoSS® Shell offers a solution by providing a secure enclosure for single-use bags, shielding biologics during transportation, freeze-thaw cycles, and storage. Its versatility and compatibility with various bag sizes and manufacturers ensure consistent protection from physical stress, which might lead to bag ruptures and product loss.
RoSS® Shell 提供了一种解决方案，它为一次性包装袋提供安全的封闭空间，在运输、冻融循环和储存过程中保护生物制剂。其通用性以及与各种尺寸和制造商的包装袋的兼容性，确保了对可能导致包装袋破裂和产品损失的物理应力的持续保护。
Moreover, the RoSS® Shell's stackable design optimizes storage space, making it ideal for streamlining cold chain logistics. It represents a significant advancement in biologic protection, offering reliability and efficiency throughout the supply chain.
此外，RoSS® Shell 的可堆叠设计优化了存储空间，使其成为简化冷链物流的理想之选。它代表了生物保护领域的一项重大进步，为整个供应链提供了可靠性和效率。

RoSS® Shell | Protecting single-use bags一次性袋子保护壳 The safest transport solution for all available single-use bioprocess containers. Robust. Scalable. Single-use bag independent. 适用于所有一次性生物工艺容器的安全运输解决方案。坚固耐用、可扩展、无需使用一次性包装袋。

 
Putting the puzzle together – platform solutions by Single Use Support
拼图游戏——Single Use Support 的平台解决方案
Single Use Support integrates a suite of platform solutions tailored to the various demands of biopharmaceutical production. One of the key elements in the product portfolio is the RoSS.pFTU platform for freeze/thaw processes in the production of biologics, featuring scalable units adaptable to diverse batch sizes and bag types. This system based on plate freezing ensures meticulous control over the process of freezing biologics, safeguarding the integrity of valuable biopharmaceuticals.
Single Use Support 整合了一系列平台解决方案，旨在满足生物制药生产的各种需求。其产品组合中的关键要素之一是 RoSS.pFTU 平台，该平台用于生物制剂生产中的冻融工艺，配备可扩展单元，能够适应不同的批次大小和包装袋类型。该系统基于平板冻融技术，可确保对生物制剂冻融过程进行精确控制，从而保障珍贵生物制药的完整性。
Should even lower temperatures be required, Single Use Support also offers RoSS.LN2F – a cryogenic freezer that is able to reach temperatures as low as -170°C in a controlled manner.
如果需要更低的温度，Single Use Support 还提供 RoSS.LN2F——一款能够以可控方式达到低至 -170°C 的低温冷冻机。
Moreover, fluid management solutions for biosimilars and biologics offer unmatched versatility and efficacy, seamlessly fitting into existing manufacturing workflows. With a focus on quality, safety, and scalability, the RoSS.FILL solutions are designed for the fluid transfer of delicate substances.
此外，用于生物类似药和生物制剂的流体管理解决方案具有优秀的多功能性和高效性，可无缝集成到现有的生产流程中。RoSS.FILL 解决方案专注于质量、安全性和可扩展性，专为易损物质的流体转移而设计。
In order to provide a safe and resource effective storage solution for biologics and biosimilars, Single Use Support has developed the ultra-low temperature freezer RoSS.ULTF, with customizable inner shelving and elevated temperature monitoring. It provides stable temperatures down to -75°C, protecting valuable biopharmaceuticals in different primary packaging solutions and sizes.
为了给生物制剂和生物类似药提供安全高效的存储方案，Single Use Support 开发了超低温冷冻柜 RoSS.ULTF，该冷冻柜配备可定制的内部搁架和优秀的温度监控系统。它能提供低至 -75°C 的稳定温度，保护采用不同初级包装和规格的珍贵生物制药产品。
With the advanced platform solutions by Single Use Support, pharmaceutical manufacturers can rely on future-proof systems that aid in mastering the complexities in storing valuable biologics safely and with precision.
凭借 Single Use Support的优秀平台解决方案，制药企业可以信赖面向未来的系统，从而安全、精准地应对存储珍贵生物制剂的复杂挑战。