1. 无菌工艺模拟的目的

9.34 Periodic verification of the effectiveness of the controls in place for aseptic processing should include a process simulation test using a sterile nutrient media and/or surrogate in place of the product. Selection of an appropriate nutrient media should be made based on the ability of the media and/or surrogate to imitate product characteristics at all processing stages. Where processing stages may indirectly impact the viability of any introduced microbial contamination, (e.g. sterile aseptically produced semi-solids, powders, solid materials, microspheres, liposomes and other formulations where product is cooled or heated or lyophilized), alternative procedures that represent the operations as closely as possible can be developed and justified. Where surrogate materials, such as buffers, are used in parts of the process simulation, the surrogate material should not inhibit the growth of any potential contamination.

对无菌工艺的控制措施有效性的定期确认，应该包括一个使用无菌营养培养基和/或安慰剂的工艺模拟试验。根据培养基和/或安慰剂在所有工艺阶段模仿产品特性的能力，应选择适当的营养培养基。如果加工阶段可能间接影响任何引入的微生物污染的生存能力（例如无菌生产的半固体、粉末、固体材料、微球、脂质体和其他制剂，其中产品被冷却、加热或冻干），应尽可能地开发并证明能够代表操作的可替代程序。如在工艺模拟的某些地方使用替代品，如缓冲液，其不应抑制任何潜在微生物污染的生长。

2. 无菌工艺模拟的要求

9.40 Process simulation tests should be performed as part of the initial validation, with at least three consecutive satisfactory simulation tests that cover all working shifts that the aseptic process may occur in, and after any significant modification to operational practices, facilities, services or equipment (e.g. modification to the HVAC system, equipment, major facility shut down, changes to process, number of shifts and numbers of personnel etc.).

工艺模拟试验应该执行首次验证，每班应有至少三个连续符合要求的、涵盖所有无菌工艺中可能发生的换班的模拟试验, 还包括操作、设施、服务或设备（如 HVAC 系统调整、设备、主要设施关闭、工艺变更、班次数和人员数量等）。

3.再验证要求

9.40 Normally, process simulation tests (periodic revalidation) should be repeated twice a year (approximately every six months) for each aseptic process, each filling line and each shift. Each operator should participate in at least one successful APS annually. Consideration should be given to performing an APS after the last batch prior to shut down, before long periods of inactivity or before decommissioning or relocation of a line.

对于每一种无菌工艺和灌装线，工艺模拟试验(周期性再验证) 通常一年应该被重复两次(大约每六个月)，每个班次操作人员至少要每年参加。当生产线长期不使用、或者在停用或移位前，应该考虑在最后一个生产批次后进行一次无菌工艺模拟试验。

9.51 An aseptic process or filling should be subject to a repeat of the initial validation when:

在以下情况下，无菌过程或灌装应重复初始验证:

i. The specific aseptic process has not been in operation for an extended period of time.

特定的无菌生产工艺长时间未生产。

ii. There is a change to the process, equipment, procedures or environment that has the potential to affect the aseptic process or an addition of new product containers or container-closure combinations.

工艺、设备、程序或环境变更有可能影响无菌工艺，或采用新的产品容器或密封件组合。