Why controlled bottle freezing is a blast 為什么可控瓶冷凍如此有趣
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.
        藥物原料的冷凍是生產(chǎn)過程中至關(guān)重要的一步，尤其對于單克隆抗體（mAb）、抗體藥物偶聯(lián)物（ADC）和其他生物制劑等高價(jià)值產(chǎn)品而言更是如此。這些物質(zhì)對溫度波動(dòng)高度敏感，冷凍不當(dāng)會(huì)損害其穩(wěn)定性、效力以及整體質(zhì)量。因此，精準(zhǔn)控制至關(guān)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.
        盡管一次性冷凍袋作為冷凍應(yīng)用的一級包裝越來越普遍，但在生物工藝的上游和下游冷鏈流程中，一次性瓶裝甚至更大容量的散裝包裝仍然被廣泛使用。然而，由于其幾何形狀的限制，瓶子存在一些局限性，導(dǎo)致生產(chǎn)過程中面臨諸多挑戰(zhàn)，例如溫度分布不均、冷凍濃縮風(fēng)險(xiǎn)以及可擴(kuò)展性有限。制造商需要能夠保持產(chǎn)品穩(wěn)定性和完整性、滿足嚴(yán)格的監(jiān)管和操作要求，同時(shí)兼顧成本效益的解決方案。其中一項(xiàng)巨大的挑戰(zhàn)是掌握冷凍工藝。通過確保溫度曲線的一致性、可擴(kuò)展性和可重復(fù)性，可以保護(hù)生物制劑的分子結(jié)構(gòu)。隨著行業(yè)向更靈活高效的生產(chǎn)環(huán)境發(fā)展，優(yōu)秀的一次性瓶冷凍技術(shù)的作用日益凸顯。
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.
        速凍機(jī)長期以來一直是解決方案的一部分，但創(chuàng)新正在重新定義其應(yīng)用范圍。像 RoSS.BLST 這樣的新一代系統(tǒng)正在為生物制藥行業(yè)的瓶裝冷凍樹立新的標(biāo)準(zhǔn)。它們具有更精準(zhǔn)的溫度控制和更智能的模塊化設(shè)計(jì)。

Figure 1: Human-machine interface of RoSS.BLST for controlled blast freezing 圖 1：RoSS.BLST 可控速凍的人機(jī)界面

CONTROLLED | BLAST FREEZING PERFORMANCE 可控 | 速凍性能
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.
        保持穩(wěn)定可控的冷凍條件對于維持瓶裝敏感生物制藥產(chǎn)品的穩(wěn)定性至關(guān)重要。RoSS.BLST 采用 1800 立方米/小時(shí)的大流量氣流系統(tǒng)，確保整個(gè)冷凍室內(nèi)的溫度分布均勻。這有助于實(shí)現(xiàn)緩慢均勻的冷凍，溫度可低至 -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
        這種可控冷卻性能與研究結(jié)果相符，該研究強(qiáng)調(diào)約 -0.1 °C/min 的冷凍速率是大限度減少冷凍濃縮效應(yīng)并保持蛋白質(zhì)完整性的優(yōu)秀速率。 RoSS.BLST 的技術(shù)配置和設(shè)計(jì)支持這些推薦的冷凍速率，有助于減少生物制劑在凍融循環(huán)過程中受到的應(yīng)力（見圖 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.
        與靜態(tài)冷凍方法相比，高速氣流冷凍方法具有更高的導(dǎo)熱性和更均勻的溶質(zhì)和蛋白質(zhì)分布，因此不易導(dǎo)致一次性瓶內(nèi)冷凍濃縮水平升高。對比結(jié)果表明，氣流式系統(tǒng)比靜態(tài)冷凍機(jī)更能有效地控制溫度梯度，這對于蛋白質(zhì)穩(wěn)定性和整體產(chǎn)品質(zhì)量尤為重要。

Median freeze run temperature curve (n = 192 bottles) 中位冷凍運(yùn)行溫度曲線（n = 192 瓶）

Figure 2: Exemplary controlled-rate freeze run of 192 bottles down to -80 °C with RoSS.BLST
圖 2：使用 RoSS.BLST 對 192 瓶樣品進(jìn)行控制速率冷凍至 -80 °C 的示例實(shí)驗(yàn)

MULTIFUNCTIONAL | FREEZE, THAW, SHAKE 多功能 | 冷凍、解凍、搖晃
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.
        除了冷凍功能外，RoSS.BLST 還支持一系列增強(qiáng)工藝控制和操作靈活性的功能。冷凍和解凍均可按控制速率進(jìn)行，這對于維持溫度敏感型生物制劑的穩(wěn)定性尤為重要。
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.
        在解凍過程中，系統(tǒng)集成了搖動(dòng)功能，并且通常是優(yōu)選擇，因?yàn)樗兄谌萜鲀?nèi)溫度均勻分布。這對于防止局部出現(xiàn)過熱或過冷點(diǎn)至關(guān)重要，這些局部過熱或過冷點(diǎn)會(huì)導(dǎo)致復(fù)溶不均勻、蛋白質(zhì)聚集或相分離。搖動(dòng)還有助于大限度地減少濃度梯度的形成，尤其是在高粘度或冷凍濃縮溶液中?？刂平鈨龊椭鲃?dòng)攪拌相結(jié)合，可降低變性風(fēng)險(xiǎn)，并確保整個(gè)批次產(chǎn)品質(zhì)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.
        該系統(tǒng)旨在滿足符合 GMP、FDA 和歐盟 Annex 1 標(biāo)準(zhǔn)的驗(yàn)證和確認(rèn)要求。這有助于在不同市場實(shí)現(xiàn)合規(guī)性，并簡化技術(shù)轉(zhuǎn)移或放大生產(chǎn)過程中的文件工作。它還可以集成到制造執(zhí)行系統(tǒng)(MES) 和企業(yè)資源計(jì)劃 (ERP) 平臺(tái)中，從而實(shí)現(xiàn)自動(dòng)化數(shù)據(jù)記錄和過程控制。

COMPACT | LOW FOOTPRINT PER LITER 體積小巧 | 每升占地面積小
Cleanroom space is often limited and costly. This makes space utilization a key consideration in biopharmaceutical production.
       潔凈室空間通常有限且成本高昂。因此，空間利用率是生物制藥生產(chǎn)中的關(guān)鍵考量因素。
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.
       鑒于此，RoSS.BLST 的設(shè)計(jì)旨在實(shí)現(xiàn)占地面積和裝載能力之間的優(yōu)秀平衡。該系統(tǒng)擁有 2.5 立方米（88.29 立方英尺）的可用腔室容積，具備同類產(chǎn)品中優(yōu)秀的容積/占地面積比，可輕松適應(yīng)緊湊型環(huán)境。它最多可容納 192 瓶，每瓶容量為 2 升，使制造商能夠在有限的設(shè)施空間內(nèi)大限度地提高生產(chǎn)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，該系統(tǒng)將溫度控制單元集成到主殼體中，無需單獨(dú)安裝，從而簡化了布局規(guī)劃。對于希望在不影響批次大小的前提下優(yōu)化空間效率的工廠而言，這種配置提供了一種切實(shí)可行的解決方案。

SUSTAINABLE | NATURAL REFRIGERANTS 可持續(xù) | 天然制冷劑
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.
       在制藥環(huán)境中，制冷系統(tǒng)越來越需要滿足可持續(xù)發(fā)展標(biāo)準(zhǔn)，同時(shí)確保安全性和性能不受影響。RoSS.BLST 采用天然制冷劑丙烷 (R290) 和乙烷 (R170)。其制冷劑充注量低于 500 克，有助于減少對環(huán)境的影響，同時(shí)保持系統(tǒng)完整性。由于制冷劑充注量低，該速凍機(jī)可放置在標(biāo)準(zhǔn)房間內(nèi)，無需采取特殊的安全措施或潔凈室級別的防護(hù)措施，例如無需 ATEX 防爆通風(fēng)系統(tǒng)。
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.
       該速凍機(jī)采用密封結(jié)構(gòu)，符合 EN378 和 ISO5149 標(biāo)準(zhǔn)。它配備氣體檢測系統(tǒng)，可在制冷劑泄漏時(shí)提供額外的保護(hù)，同時(shí)確保運(yùn)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.
這種設(shè)計(jì)方案提高了生產(chǎn)設(shè)施的安裝靈活性，并符合當(dāng)前的環(huán)保和安全法規(guī)。它體現(xiàn)了整個(gè)行業(yè)致力于大限度減少溫控工藝對環(huán)境影響的趨勢。

FLEXIBLE | MODULAR INTERIOR 靈活 | 模塊化內(nèi)飾In biopharmaceutical multi-product facilities, the efficient and safe handling of a variety of packaging formats presents significant challenges.
        在生物制藥多產(chǎn)品生產(chǎn)設(shè)施中，高效安全地處理各種包裝規(guī)格是一項(xiàng)重大挑戰(zhàn)。
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 的設(shè)計(jì)旨在容納不同類型的大體積初級包裝，從標(biāo)準(zhǔn)瓶到更大的二維或三維容器。該速凍機(jī)采用模塊化貨架系統(tǒng)，可調(diào)節(jié)的貨架能夠適應(yīng)不同尺寸的容器。這使得單個(gè)設(shè)備即可處理多種產(chǎn)品和工作流程，為合同研發(fā)生產(chǎn)機(jī)構(gòu) (CDMO) 提供了所需的靈活性，因?yàn)樵谶@些機(jī)構(gòu)中，包裝規(guī)格的切換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.
        其內(nèi)部結(jié)構(gòu)無需額外設(shè)備即可重新配置，以適應(yīng)不斷變化的生產(chǎn)量或包裝要求，因此也支持可擴(kuò)展的瓶裝工藝。這簡化了規(guī)劃，并提高了可用資源的整體利用率。


Figure 4: Modular interior design for single-use bottles and other primary packaging 圖 4：一次性瓶子和其他初級包裝的模塊化內(nèi)部設(shè)計(jì)

From bottlenecks to breakthroughs 從瓶頸到突破
While blast freezers are well-established in biopharmaceutical manufacturing, challenges remain, especially in efficiently and consistently freezing single-use bottles without compromising product integrity.
        盡管速凍機(jī)在生物制藥生產(chǎn)中應(yīng)用廣泛，但仍存在一些挑戰(zhàn)，尤其是在高效、穩(wěn)定地冷凍一次性瓶裝產(chǎn)品而不損害其完整性方面。
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 正好滿足了這一需求。它不僅僅是一臺(tái)普通的速凍機(jī)，它將高性能冷凍與模塊化設(shè)計(jì)相結(jié)合，支持與不同類型容器的兼容性、可擴(kuò)展性和自動(dòng)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.
        這款速凍機(jī)由 Single Use Support 公司開發(fā)，是模塊化端到端瓶裝解決方案的一部分，該方案涵蓋了整個(gè)流體和冷鏈管理流程（見圖 6）。在冷凍之前，該流程采用 IRIS 瓶組件和 RoSS.FILL 無菌灌裝機(jī)進(jìn)行無菌灌裝，從而實(shí)現(xiàn)封閉式流體管理，并支持高效、安全地灌裝到瓶中。至關(guān)重要的是，它還包括保護(hù)性的一次性耗材，可在每個(gè)步驟大限度地保障產(chǎn)品的安全性和完整性。作為該系統(tǒng)的一部分，Bottle RoSS 提供了一種可靠的二級包裝解決方案，可在冷鏈處理過程中保護(hù)瓶蓋上的管路和組件免受損壞。其設(shè)計(jì)確保在自動(dòng)化冷凍流程中安全操作，并兼容大多數(shù)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.
        這款優(yōu)秀的速凍機(jī)能夠彌補(bǔ)現(xiàn)有工藝的不足，幫助制造商獲得更強(qiáng)的控制力、更高的產(chǎn)量和更優(yōu)秀的產(chǎn)品質(zhì)量。

Figure 5: Robust secondary packaging for bottle tubing with Bottle RoSS 圖 5：采用 Bottle RoSS 的堅(jiān)固型瓶管二級包裝

Figure 6: End-to-end fluid and cold chain process for bottles圖 6：瓶裝液體和冷鏈的端到端流程