一次性使用工藝元件 | ASME BPE-2022 新增内容解讀

一次性使用技術應用于制藥領域已有30餘年曆史。憑借其聚合物材料可塑性強、便于運輸和使用的優勢，在品質可控的前提下，一次性使用系統已經廣泛應用于液體儲存、液體轉移、無菌過濾、超濾和透析換液，以及病人使用的打點滴系統等。近年來，随着單抗藥物和細胞治療藥物的成功發展，相關技術迅速更新，一次性使用技術在制藥領域的應用不斷拓展。目前一次性使用技術幾乎可以涵蓋整個生物制藥工藝過程的各個單元操作。

ASME BPE 2022已釋出，本次版本更新，增加了一次性使用部件群組件的要求，分為三個章節，分别是第七章一次性使用設計、第八章一次性使用工藝元件和第九章一次性使用的制造、組裝和安裝。本文繼續介紹第八章一次性使用工藝元件。

一次性使用工藝元件

1.蒸汽直通和蒸汽直通連接配接器

蒸汽直通和蒸汽直通連接配接器設計用于将一次性系統連接配接至多次使用（金屬）系統。蒸汽直通和蒸汽直通連接配接器應：

(a)形成符合DT和MC部分要求的衛生夾緊接頭

(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相容，滅菌後（例如，伽馬輻照）在266°F（130°C）下持續1小時（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。

2.無菌連接配接器

無菌連接配接器允許連接配接一次性元件，同時在連接配接之前、期間和之後保持工藝接觸表面無菌，而不考慮制造環境。

2.1制造商責任

制造商應：

(a)進行微生物侵入試驗，以确認連接配接後無菌液路不會受到損害

(b)定義連接配接器是幹連接配接器還是濕連接配接器

(1)幹燥意味着液體不能進入連接配接器。使用前，必須使用夾鉗或其他合适的技術将液體與連接配接器隔離。

(2)濕意味着連接配接器中可以有液體進行連接配接。

(c)提供産品規格，包括但不限于以下内容：

(1)溫度額定值

(2)壓力額定值

(3)滅菌方法的相容性（例如，伽馬滅菌，高壓滅菌）

(4)産品流路清潔度（微粒、内毒素、生物負載）

(5)流速

(d)定義連接配接器兩半部分的性别

(1)獨特的陽半部分和陰半部分

(2)沒有性别，每一半都是一樣的

(e)定義連接配接是設計用于一次性連接配接還是多個連接配接

(1)設計用于一次性連接配接的連接配接器應具有不可逆的鎖定機制，除非其專門設計用于無菌斷開。

(2)設計用于多重連接配接和斷開的連接配接器應具有規定的最大連接配接數。

(f)提供裝配說明，以確定正确連接配接

2.2 所有者/使用者責任

所有者/使用者應

(a)根據所有适用過程和滅菌條件的服務要求，審查制造商的品質标準

(b)確定由經過适當教育訓練的操作員按照合格程式進行連接配接，以保持系統完整性

3.柔性生物工藝容器（袋）

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、儲存、取樣、轉移和運輸元件中。一次性袋具有連接配接端口，并與管路或管路支路結合使用，以實作灌裝、配置設定、取樣和其他工藝功能。本節提供了對一次性袋結構材料和鑒定的要求。

3.1材料

多層膜通常用于制造一次性袋。制造商應确定袋的所有薄膜和連接配接層的構造材料。對于預期用于過程接觸的袋，制造商應識别所有材料（例如，主要材料、粘結層和添加劑），這些材料可能會摻雜袋内産品。

3.2确認

制造商應提供一次性袋的工作溫度和壓力限值。制造商應規定适當的滅菌方法，包括暴露範圍、滅菌後有效期和其他限制。制造商應提供處理和安全使用程式，包括懸挂限制、填充限制和二次密封建議。

4.高分子衛生接頭

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.