翻译_tr28_无菌原料药bpcs的工艺模拟_processsimulation_20xxpdf

翻译_tr28_无菌原料药bpcs的工艺模拟_processsimulation_20xxpdf内容摘要：

s environmental monitoring, qualification of personnel and validation of cleaning and sterilization cycles, it is possible to maintain the level of asepsis demonstrated during the process simulation test. 但是，通过控制和相关的进程的验证，如环境监测，人员评估和清洗验证以及消毒周期验证，它有可能在这个工艺模拟测试中保持无菌水平。 Therefore, it is important to validate the related sanitization and sterilization processes independently, such as sterilization/depyrogenation of the product, sterilization of the process equipment including product contact surfaces, sterilization of containers (intermediate and final packaged bulk), and support systems such as air, water, or nitrogen (6, 7, 8). 因此，重要的是要独立验证相关的消毒和灭菌过程， 例如灭菌 /产品的除热原，工艺设备的灭菌，包括产品接触表面，容器的灭菌（中间产品和最终包装），支持系统，如空气，水，或氮（ 6， 7， 8）。 Confidence in the sterility of a specific production lot is gathered through a number of process controls and procedures including: documented and validated sterilization/sanitization procedures, inprocess controls regulating the production process, environmental monitoring, prehensive batch records, extensive qualification of process equipment, and training of operating personnel. 对一个具体生产批次的无菌的确信是通过过程控制和程序的序列号来收集，包括：被记载和验证过的杀菌 /消毒程序，对 生产过程监察的实时过程控制，环境监测，全面记录，工艺设备的全方位条件，和培训操作人员。 2. PROCESS SIMULATION CONCEPTS AND PRINCIPLES 工艺模拟的概念和原理 . Number and Frequency of Tests 实验的次数和频率 For a new facility or production process, process simulations can be performed as part of the overall validation. Initial process simulation tests, if performed, are conducted after equipment qualification, sterilization process validation, and personnel training have been performed, and environmental monitoring has demonstrated that the new facility is under the desired state of control (9, 10, 11). If a process simulation test fails in the absence of this supportive work, identification of a possible root cause will usually be more difficult. Three consecutive successful process simulation tests are performed when evaluating a new facility or process. Prior to release of the new facility, or new process for production use, acceptable results from these process simulation tests should be achieved to demonstrate the reproducibility of the process. 对应一个新的设施或 生产工艺，工艺模拟应该作为所有验证的一部分。 最初的工艺验证应该在设备确认、灭菌工艺验证、人员培训已经完成并且环境监测证明新的设施已经在预期的状态中受控之后进行 (9, 10, 11)。 如果没有作这些支持性的工作，工艺模拟实验失败的话，将很难确定可能的原因。 当确认一个新的设施或工艺时，验证一个工艺应该进行三次连续成功的模拟工艺实验。 在为生产使用正式批准一个新的设施、新的工艺之前，应该完成这样连续的可接受的结果，以证明工艺的可重复性。 In existing facilities, a process simulation test program should be considered for each aseptic process. Additional process simulation tests may be considered to evaluate changes to procedures, practices or equipment configuration (See Section 11— Periodic Reassessment). 在现有设施，过程模拟测试程序应被考虑到每 个无菌过程。 追加工艺模拟试验可被用来评估程序、实践或设备配置的变更（见第 11期再评估表）。 Process simulations for closed systems can be performed after sterilization to confirm the acceptable sterilization of the systems as well as the appropriateness of the procedures employed within. The duration of campaigns for closed system may be established through physical monitoring of such aspects as pressure differentials, leak rates, filter integrity tests, etc. and is further supported by a preventive maintenance program. End of campaign process simulations are thus not required for the closed portions of a process system. The duration of campaigns for open systems may be confirmed through appropriate process simulations conducted at the end of a real or simulated campaign. 封闭系统的过程模拟可以在灭菌后实施，以确认该系统的灭菌合格性以及内部程序的适当性。 在封闭系统的工作持续时间可能将通过如压力差，泄漏率，过滤器完整性测试等物理等方面的监测来被确定，并进一步被预防性维修计划所支持。 工作过程模拟的完成不需要一个工艺系统的封闭部分。 开放系统的工作持续时间可能通过真实或模拟的工作结束时进行的适当的工艺模拟来被确认。 . Worst Case 最差条件 One of the more prevalent techniques used in the validation of pharmaceutical processes is the employment of worst case scenarios. 在制药工艺验证中最常采用的技术之一是采用“最差条件”。 The use of worst case situations is intended to provide a greater challenge to the process, system or equipment being validated than that experienced under routine processing “最差条件” 是有意对工艺、系统、设备在更高的挑战条件下进行验证。 If, under the circumstances of the worst case challenge, acceptable results are achieved, then there is greater confidence in the reliability of the system under more normal situations. 如 果在“最差条件”的挑战下，仍能够达到预期的可接受标准，那么在正常条件下，对系统的可靠性将有更高的信心。 Process simulation tests readily lend themselves to worst case challenges. Some of the types of challenges which may be employed where possible are: 工艺模拟实验很容易进行“最差条件”的挑战。 下面提供了一些类型的挑战： • using materials, equipment, utensils and other items which have remained in the aseptic processing area for extended periods after sterilization。 使用的原料、设备、器具等在灭菌后于无菌工艺区保留时间超出期限。 • using the maximum number of personnel necessary to process the batch。 使用人员数超过灌装工艺所需。 • increasing the time period between the pletion of equipment sterilization and the start of the process simulation。 设备消毒的完成与开始模拟之间时间间隔过长 • using a growth promoting medium or placebo material in the process simulation test rather than an inhibitory material。 在工艺模拟实验中使用促生长培养基或安慰剂，而不是使用有抑制性的处方。 • performing a process simulation test after pletion of the last lot in a production campaign。 在最后的生产完成后进行工艺模拟实验。 The conduct of a process simulation for a sterile bulk typically includes activities and manipulations that are specific for its execution. 对于无菌原料的工艺模拟的进行通常包括大量特定的活动和操作。 These added steps introduce a higher potential for contamination than is inherent in the routine process and pose an increased risk for process simulation failure. 相比固有的常规工艺，这些额外的步骤导 致了更高的潜在污染，增加了过程模拟失败的风险。 In the development of protocols or procedures used for the definition of process simulation tests, the use of worst case challenges such as those described above is an essential element of a wellfounded program. 在建议用于定义工艺模拟试验的方案 或过程时，一个有良好根据的程序会使用上面提到的“最差条件”的挑战。 T。