The situation 情況

The bottle: Friend & foe in bioprocessing 瓶子：生物加工中的朋友和敵人

Despite the growing shift toward single-use bags, sterile bottles remain a staple in many biopharmaceutical workflows, such as
盡管人們?cè)絹?lái)越多地轉(zhuǎn)向使用一次性袋子，但無(wú)菌瓶仍然是許多生物制藥工作流程中的主要組成部分，例如

• Early-stage development 早期開發(fā)

• Small-volume fills 小容量分裝

• Stability studies 穩(wěn)定性研究

• Buffer, media, solution addition 緩沖液、培養(yǎng)基、溶液添加

Their rigid structure and compatibility with existing lab infrastructure make them a reliable choice in specific scenarios.
它們的堅(jiān)固結(jié)構(gòu)和與現(xiàn)有實(shí)驗(yàn)室基礎(chǔ)設(shè)施的兼容性使其成為特定場(chǎng)景中的可靠選擇。

Bottles present limitations in modern bioprocessing: Fluid management utilizing bottles is less scalable and difficult to automate. Additionally, bottles pose contamination risks due to open handling while also delivering inconsistent freezing results.
在現(xiàn)代生物工藝中，瓶子的使用存在諸多限制：使用瓶子進(jìn)行液體管理的可擴(kuò)展性較差，且難以實(shí)現(xiàn)自動(dòng)化。此外，瓶子由于采用開放式操作，存在污染風(fēng)險(xiǎn)，并且會(huì)導(dǎo)致冷凍結(jié)果不一致。

However, advanced bottle filling technologies can turn this “foe" into a trusted “friend", tackling these challenges with precision and sterility.
然而，先進(jìn)的瓶裝技術(shù)可以將這個(gè)“敵人"變成值得信賴的“朋友"，以精準(zhǔn)和無(wú)菌的方式應(yīng)對(duì)這些挑戰(zhàn)。

Case: Media filling into single-use bottles and 3D bags 案例：填充至一次性瓶和3D袋中

A biopharmaceutical manufacturer based in Latin America specializes in the production of liveattenuated vaccines. The upstream processing (USP) of these vaccines focuses on highdensity cell cultures, which are later used for virus activation and amplification. For these bioprocessing steps in cell expansion and virus propagation it is required to use media and buffer solutions.
一家位于拉丁美洲的生物制藥制造商專門生產(chǎn)減毒活疫苗。這些疫苗的上游加工（USP）側(cè)重于培養(yǎng)高密度細(xì)胞，隨后用于病毒的激活和擴(kuò)增。在細(xì)胞擴(kuò)增和病毒增殖的這些生物加工步驟中，需要使用培養(yǎng)基和緩沖液。

To maintain sterility and process flexibility, the company uses single-use bottles and 3D bags for aseptic media filling. The process accommodates a wide range of container formats – from bottles of 30mL to 2000mL, to large 3D single-use bags ranging from 50L to 200L.
為了保持無(wú)菌性和工藝靈活性，該公司采用一次性瓶和3D袋進(jìn)行無(wú)菌培養(yǎng)基分裝。該工藝適用于各種容器規(guī)格——從30毫升到2000毫升的瓶子，到50升到200升的大型3D一次性袋。

The challenge 挑戰(zhàn)

Complex media filling operations 復(fù)雜的培養(yǎng)基分裝操作

Due to the large variety and quantity of containers – up to 20 single-use bottles and 3D bags per batch – the manufacturer faces significant operational challenges.
由于容器種類繁多、數(shù)量龐大——每批次多達(dá)20個(gè)一次性瓶和3D包裝袋——制造商面臨著巨大的運(yùn)營(yíng)挑戰(zhàn)。

This complexity reduces efficiency and limits flexibility, particularly when adapting to varying batch sizes or container formats. Manual filling in a biosafety cabinet or isolator carries significant safety risks, raising the chance of contamination and jeopardizing product sterility. Together, these factors impede scalability and process robustness—making automation and closed-system solutions ever more essential.
這種復(fù)雜性降低了效率，并限制了靈活性，尤其是在適應(yīng)不同的批次大小或容器規(guī)格時(shí)。在生物安全柜或隔離器中手動(dòng)分裝存在重大安全風(fēng)險(xiǎn)，會(huì)增加污染的可能性，并危及產(chǎn)品的無(wú)菌性。這些因素共同阻礙了可擴(kuò)展性和工藝的穩(wěn)健性——這使得自動(dòng)化和封閉系統(tǒng)解決方案變得更加重要。

The solution 解決方案

Making bottle filling a closed system 使瓶子分裝成為一個(gè)封閉的系統(tǒng)

In aseptic manufacturing, converting bottle filling into a fully closed system is a key step in preserving product sterility across the entire fluid management process. This is achieved by using bottle caps equipped with sterile venting filters or venting bags that allow for pressure equalization during automated filling without exposing the product to the environment. Customizable singleuse bottle assemblies can be specifically designed to integrate with automated bottle filling systems, eliminating the need for manual intervention. The result: reduced contamination risk, assured GMP compliance (including Annex 1), and less reliance on high-grade cleanroom facilities.
在無(wú)菌生產(chǎn)中，將瓶裝分裝系統(tǒng)轉(zhuǎn)換為全封閉系統(tǒng)是在整個(gè)流體管理過(guò)程中保持產(chǎn)品無(wú)菌的關(guān)鍵步驟。這可以通過(guò)使用配備無(wú)菌排氣過(guò)濾器或排氣袋的瓶蓋來(lái)實(shí)現(xiàn)，這些過(guò)濾器或排氣袋可以在自動(dòng)分裝過(guò)程中保持壓力平衡，而不會(huì)將產(chǎn)品暴露在環(huán)境中。可定制的一次性瓶組件可以專門設(shè)計(jì)用于與自動(dòng)瓶裝分裝系統(tǒng)集成，從而無(wú)需人工干預(yù)。結(jié)果：降低污染風(fēng)險(xiǎn)，確保符合GMP標(biāo)準(zhǔn)（包括附錄1），并減少對(duì)高級(jí)潔凈室設(shè)施的依賴。

One size fills all: Automated & precise bottle filling with RoSS.FILL 一種尺寸適合所有情況：RoSS.FILL 自動(dòng)精準(zhǔn)分裝

Accommodating a wide range of container types and volumes, RoSS.FILL Bottle delivers a highly flexible and scalable solution for automated filling of both bottles and 3D single-use bags. Engineered for manufacturing cleanrooms, the system supports closed-system filling, ensuring precise, pressure-balanced operation and batch consistency for GMPcompliant dispensing.
RoSS.FILL Bottle 適用于各種類型和容量的容器，為瓶子和 3D 一次性包裝袋的自動(dòng)分裝提供了高度靈活且可擴(kuò)展的解決方案。該系統(tǒng)專為潔凈室制造而設(shè)計(jì)，支持封閉式系統(tǒng)分裝，確保精準(zhǔn)、壓力平衡的運(yùn)行和批次一致性，從而符合 GMP 要求。

Its modular design enables seamless setup changes, making it ideal for multiproduct facilities and dynamic production needs. The vaccine manufacturer was now able to use a setup with different racks connected to a single control unit to fill large volumes of media and buffer solution. This made it possible to fill both bottles and bags using the same system, tailored to the required packaging format (see figure 4).
其模塊化設(shè)計(jì)可實(shí)現(xiàn)無(wú)縫設(shè)置更改，使其成為多產(chǎn)品設(shè)施和動(dòng)態(tài)生產(chǎn)需求的理想選擇。現(xiàn)在，該疫苗制造商能夠使用連接到單個(gè)控制單元的不同支架的裝置來(lái)分裝大量培養(yǎng)基和緩沖液。這使得能夠使用同一系統(tǒng)同時(shí)分裝瓶子和包裝袋，并根據(jù)所需的包裝規(guī)格進(jìn)行定制（見(jiàn)圖 4）。

The result 結(jié)果

Being able to fill bottles of varying sizes and volumes has markedly improved operational efficiency over manual methods. Specifically, the vaccine manufacturer reported the following benefits for bottle filling:
與手動(dòng)方法相比，能夠分裝不同尺寸和容量的瓶子顯著提高了操作效率。具體來(lái)說(shuō)，疫苗制造商報(bào)告了瓶子分裝的以下優(yōu)勢(shì)：

• More than 3 times faster filling 分裝速度提高 3 倍以上

Including preparation, filling, and documentation in a sterile environment, the manual process averages 5 hours, while automation completes the task in just over 1 hour. Dispensing 150 liters into 96 single-use 2-liter bottles was thus approximately 70% faster with RoSS.FILL than with manual handling.
包括在無(wú)菌環(huán)境中的準(zhǔn)備、分裝和記錄，手動(dòng)流程平均耗時(shí) 5 小時(shí)，而自動(dòng)化流程僅需 1 個(gè)多小時(shí)即可完成。因此，使用 RoSS.FILL 將 150 升液體分裝到 96 個(gè) 2 升一次性瓶中，比手動(dòng)操作快約 70%。

• Only 1 operator needed 僅需 1 名操作員

Including material handing and quality control, a standard manual filling process requires two to three operators, whereas automated filling machines can be operated by one person. All documentation is fully recorded in accordance with 21 CFR Part 11 requirements.
包括物料處理和質(zhì)量控制在內(nèi)，標(biāo)準(zhǔn)的手動(dòng)分裝流程需要兩到三名操作員，而自動(dòng)分裝機(jī)只需一人即可操作。所有文件均按照21 CFR Part 11的要求完整記錄。

The time saved in filling bottles and bags in parallel increases significantly when relying on automatic filling. This is especially true with modular systems, which enable both containers to be filled using one system.
采用自動(dòng)分裝技術(shù)，可顯著節(jié)省同時(shí)分裝瓶子和袋子的時(shí)間。模塊化系統(tǒng)尤其如此，它允許使用一個(gè)系統(tǒng)同時(shí)分裝兩個(gè)容器。

Additional benefits with closed bottle filler 封閉式分裝機(jī)的額外優(yōu)勢(shì)

• Aseptically closed system: Using a closed system significantly reduces the risk of human error and exposure to bioburden, especially when working with sensitive biologics, by minimizing open transfers and operator interaction. 無(wú)菌密閉系統(tǒng)：使用密閉系統(tǒng)可顯著降低人為失誤和生物負(fù)載暴露的風(fēng)險(xiǎn)，尤其是在處理敏感生物制劑時(shí)，因?yàn)樗梢宰畲笙薅鹊販p少開放式轉(zhuǎn)移和操作員互動(dòng)。

• Accuracy: Filling processes can be tailored to meet strict customer requirements – such as ±100g for large bags an ±10g for bottles – ensuring consistent and compliant output. 準(zhǔn)確性：分裝流程可根據(jù)嚴(yán)格的客戶要求進(jìn)行定制，例如大袋±100克，瓶裝±10克，從而確保輸出的一致性和合規(guī)性。

• Recovery rate: The system enables maximum recovery rates of any drug substance or drug product, minimizing waste and maximizing yield. 回收率：該系統(tǒng)可提高任何原料藥或藥品的回收率，從而最大限度地減少浪費(fèi)并提高產(chǎn)量。

• GMP compliance: Integrated software solutions that are fully compliant with 21 CFR Part 11, cGMP, and Annex 1 regulations allow supervisor-level control. These features support traceability, audit readiness, and overall process reliability. Together, they contribute to a robust and quality-driven manufacturing environment. 符合GMP標(biāo)準(zhǔn)：集成的軟件解決方案符合21 CFR第11部分、cGMP和附錄1法規(guī)，可實(shí)現(xiàn)主管級(jí)控制。這些功能支持可追溯性、審計(jì)準(zhǔn)備度和整體流程可靠性。它們共同構(gòu)成了強(qiáng)大且以質(zhì)量為導(dǎo)向的生產(chǎn)環(huán)境。

• Integrated into the end-to-end bottle process: Like with single-use bags, Single Use Support offers complete solutions for the entire fluid and cold chain management of bottles. These include: 集成到端到端瓶裝流程中：與一次性包裝袋一樣，一次性支持系統(tǒng)為整個(gè)瓶裝液體和冷鏈管理提供完整的解決方案。這些解決方案包括：

• IRIS Bottle Assemblies: Single-use tubing and manifold assemblies developed for your fluid transfer processes in biopharma processes. IRIS 瓶組件：專為生物制藥工藝中的流體輸送流程而開發(fā)的一次性管路和歧管組件。

• Bottle RoSS®: Protects tubing assemblies and bottle caps during freezing to ensure product integrity.  RoSS® 瓶：在冷凍過(guò)程中保護(hù)管路組件和瓶蓋，確保產(chǎn)品完整性。

• RoSS.BLST: GMP-compliant system for blast freezing & thawing of drug substances – suitable for any primary packaging, including bottles. RoSS.BLST：符合 GMP 標(biāo)準(zhǔn)的藥物速凍和解凍系統(tǒng)，適用于任何初級(jí)包裝，包括瓶裝。

lRoSS.ULTF: Ultra-low temperature storage freezer for frozen drug substances in any primary packaging, maintaining stable temperatures down to -80°C  
RoSS.ULTF：超低溫冷凍柜，適用于任何初級(jí)包裝的冷凍藥物，可在低至 -80°C 的溫度下保持穩(wěn)定溫度。