一次性使用技術(shù)應(yīng)用于制藥領(lǐng)域已有30余年歷史。憑借其聚合物材料可塑性強(qiáng)、便于運(yùn)輸和使用的優(yōu)勢(shì)，在質(zhì)量可控的前提下，一次性使用系統(tǒng)已經(jīng)廣泛應(yīng)用于液體儲(chǔ)存、液體轉(zhuǎn)移、無菌過濾、超濾和透析換液，以及病人使用的輸液系統(tǒng)等。近年來，隨著單抗藥物和細(xì)胞治療藥物的成功發(fā)展，相關(guān)技術(shù)迅速升級(jí)，一次性使用技術(shù)在制藥領(lǐng)域的應(yīng)用不斷拓展。目前一次性使用技術(shù)幾乎可以涵蓋整個(gè)生物制藥工藝過程的各個(gè)單元操作。
ASME BPE 2022已發(fā)布，本次版本升級(jí)，增加了一次性使用部件和組件的要求，分為三個(gè)章節(jié)，分別是第七章一次性使用設(shè)計(jì)、第八章一次性使用工藝組件和第九章一次性使用的制造、組裝和安裝。本文繼續(xù)介紹第八章一次性使用工藝組件。
蒸汽直通和蒸汽直通連接器設(shè)計(jì)用于將一次性系統(tǒng)連接至多次使用（金屬）系統(tǒng)。蒸汽直通和蒸汽直通連接器應(yīng)：
(a)形成符合DT和MC部分要求的衛(wèi)生夾緊接頭
(b)保持密封（見MC-4）
(c)可排水（見SD部分）
(d)可滅菌（參見SU-9）
(e)與SIP兼容，滅菌后（例如，伽馬輻照）在266°F（130°C）下持續(xù)1小時(shí)（暴露表面）
(f)符合PM-3.1的生物相容性要求
(g)符合表PM-2.2.1-1的符合性證書要求。
無菌連接器允許連接一次性組件，同時(shí)在連接之前、期間和之后保持工藝接觸表面無菌，而不考慮制造環(huán)境。
2.1制造商責(zé)任
制造商應(yīng)：
(a)進(jìn)行微生物侵入試驗(yàn)，以確認(rèn)連接后無菌液路不會(huì)受到損害
(b)定義連接器是干連接器還是濕連接器
(1)干燥意味著液體不能進(jìn)入連接器。使用前，必須使用夾鉗或其他合適的技術(shù)將液體與連接器隔離。
(2)濕意味著連接器中可以有液體進(jìn)行連接。
(c)提供產(chǎn)品規(guī)格，包括但不限于以下內(nèi)容：
(1)溫度額定值
(2)壓力額定值
(3)滅菌方法的兼容性（例如，伽馬滅菌，高壓滅菌）
(4)產(chǎn)品流路清潔度（微粒、內(nèi)毒素、生物負(fù)載）
(5)流速
(d)定義連接器兩半部分的性別
(1)獨(dú)。特的陽半部分和陰半部分
(2)沒有性別，每一半都是一樣的
(e)定義連接是設(shè)計(jì)用于一次性連接還是多個(gè)連接
(1)設(shè)計(jì)用于一次性連接的連接器應(yīng)具有不可逆的鎖定機(jī)制，除非其專門設(shè)計(jì)用于無菌斷開。
(2)設(shè)計(jì)用于多重連接和斷開的連接器應(yīng)具有規(guī)定的最大連接數(shù)。
(f)提供裝配說明，以確保正確連接
2.2 所有者/用戶責(zé)任
所有者/用戶應(yīng)
(a)根據(jù)所有適用過程和滅菌條件的服務(wù)要求，審查制造商的質(zhì)量標(biāo)準(zhǔn)
(b)確保由經(jīng)過適當(dāng)培訓(xùn)的操作員按照合格程序進(jìn)行連接，以保持系統(tǒng)完整性
柔性生物處理容器，也稱為一次性袋，可在2D或3D格式中以不同的配置和體積容量獲得。這些一次性袋用于生物工藝流體或粉末的制備、儲(chǔ)存、取樣、轉(zhuǎn)移和運(yùn)輸組件中。一次性袋具有連接端口，并與管路或管路支路結(jié)合使用，以實(shí)現(xiàn)灌裝、分配、取樣和其他工藝功能。本節(jié)提供了對(duì)一次性袋結(jié)構(gòu)材料和鑒定的要求。
3.1材料
多層膜通常用于制造一次性袋。制造商應(yīng)確定袋的所有薄膜和連接層的構(gòu)造材料。對(duì)于預(yù)期用于過程接觸的袋，制造商應(yīng)識(shí)別所有材料（例如，主要材料、粘結(jié)層和添加劑），這些材料可能會(huì)摻雜袋內(nèi)產(chǎn)品。
3.2確認(rèn)
制造商應(yīng)提供一次性袋的工作溫度和壓力限值。制造商應(yīng)規(guī)定適當(dāng)?shù)臏缇椒?，包括暴露范圍、滅菌后有效期和其他限制。制造商?yīng)提供處理和安全使用程序，包括懸掛限制、填充限制和二次密封建議。
參見PM-4.4。
- 原文參考 -
CHAPTER 8 PROCESS COMPONENTS FOR SINGLE-USE
PART SC COMPONENTS FOR SINGLE-USE
SC-1 STEAM-THROUGH AND STEAM-TO CONNECTORS
Steam-through and steam-to connectors are designed to connect single-use systems to multiuse (metallic) systems. Steam-through and steam-to connections shall:
(a) form a hygienic clamp union, meeting the requirements of Parts DT and MC
(b) maintain a seal (see MC-4)
(c) be drainable (see Part SD)
(d) be sterilizable (see SU-9)
(e) be compatible with SIP, poststerilization (e.g., gamma irradiation) at 266°F (130°C) for 1 hr (exposed surfaces)
(f) meet the biocompatibility requirements of PM-3.1
(g) meet the Certificate of Conformance requirements of Table PM-2.2.1-1.
SC-2 ASEPTIC CONNECTORS
Aseptic connectors allow single-use assemblies to be joined while maintaining a sterile process contact surface before, during, and after connection, without regard to the manufacturing environment.
SC-2.1 Manufacturer Responsibilities
The manufacturer shall
(a) conduct microbial ingress testing to qualify that a sterile fluid path postconnection is not compromised
(b) define whether the connectors are dry connectors or wet connectors
(1) Dry means liquid cannot be in the connector. Pinch clamps or another suitable technique must be used to isolate the liquid from the connector prior to use.
(2) Wet means the connection can be made with liquid in the connector.
(c) provide product specifications including, but not limited to, the following:
(1) temperature ratings
(2) pressure ratings
(3) sterilization method compatibility (e.g., gamma, autoclave)
(4) product flow path cleanliness (particulates, endotoxins, bioburden)
(5) flow rates
(d) define the gender of the connector halves
(1) unique male and female halves
(2) genderless, where each half is identical
(e) define whether the connection is designed for onetime connection or multiple connections
(1) Connectors designed for a one-time connection shall incorporate an irreversible locking mechanism, unless it is specifically designed for aseptic disconnect.
(2) Connectors designed for multiple connections and disconnections shall have the maximum number of connections specified.
(f) provide assembly instructions to ensure proper connection
SC-2.2 Owner/User Responsibilities
The owner/user should
(a) review the manufacturer’s specifications against the service requirements for all applicable process and sterilization conditions
(b) ensure the connection will be performed to a qualified procedure by a properly trained operator to maintain system integrity
SC-3 FLEXIBLE BIOPROCESSCONTAINERS (BAGS)
Flexible bioprocessing containers, also referred to as single-use bags, are available in 2D or 3D format, in different configurations and volume capacities. These bags are used in assemblies for preparation, storage, sampling, transfer, and transport of bioprocess fluids or powders. The bags have connection ports and are used in conjunction with tubing or tubing manifolds to allow for filling, dispensing, sampling, and other process functions. This section provides requirements on materials of construction and qualification.
SC-3.1 Materials
Multilayer films are often used to manufacture single-use bags. The manufacturer should identify the material of construction of all film and tie layers of the bag. For bags intended for process contact, the manufacturer shall identify all materials (e.g., primary materials, tie layers, and additives) that have the potential to adulterate the bag contents.
SC-3.2 Qualifications
The manufacturer shall provide the operating temperature and pressure limits of the single-use bag. The manufacturer shall specify appropriate sterilization methods, including range of exposure, poststerilization shelf life, and other limitations. The manufacturer should provide handling and safe use procedures, including hanging restrictions, filling limitations, and secondary containment recommendations.
SC-4 POLYMERIC HYGIENIC UNIONS
See PM-4.4.
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