4.3 Design Strategy for Process Performance Qualification (PPQ)
工艺性能确认（PPQ）的设计策略
4.3.1 Use of Prior Knowledge and Stage 1 Data to Support PPQ
使用已有的知识和阶段1的数据来支持PPQ
In a lifecycle approach to process validation, sources of data and information outside of the PPQ batches may be used to support a high degree of confidence in an ongoing state of process control. Prior knowledge
is that which has been gained from similar products and processes. It may come from experience with a portfolio of similar molecules, where platform manufacturing strategies have been developed using existing facilities and equipment (e.g., platform manufacturing processes for monoclonal antibodies), or from similar process and unit operations. Leveraging the body of data from similar products and processes may provide an additional level of confidence in the process control of a product and process that uses a similar control strategy and unit operations.
工艺验证采用生命周期方法时，在持续的工艺控制状态下，PPQ批外的数据和信息用来进一步支持验证。已有的知识是指从类似产品或工艺中获得的知识。它可能来自于一组类似分子的生产经历，利用了已有的厂房和设备采用平台生产策略（例如单克隆抗体的平台生产工艺），或者来自于相似的工艺和单元操
作。借助从类似产品和工艺中获得的数据可以为那些使用类似控制策略和单元操作的产品和工艺提供额外的支持。
By contrast, first-in-class molecules and/or products manufactured in new facilities/equipment will not have a similar depth of prior knowledge and data prior to development. In these instances, increased emphasis on data gathering in Stage 1 may be applied to support PPQ readiness. To gather sufficient data to demonstrate an acceptable level of confidence in the commercial manufacturing process when little prior knowledge or Stage 1 data are available, the scope and extent of PPQ may be greater. The rationale and
scientific justification for the use of existing data (prior knowledge) to support the PPQ Stage should be documented in the process validation master plan. All prior knowledge and Stage 1 data used in to support PPQ must be retrievable, traceable, verified, and generated using good scientific practices.
与之相对，首类分子和/或在新的厂房/设备中生产的产品在开发前不会有已有的知识和数据。这时，尤其要注意收集第一阶段的数据来支持PPQ的准备。当只有少量的以前知识或第一阶段数据可以利用时，要收集到足够的数据来证明商业生产工艺可以信赖，那PPQ的范围和程度都要更大。使用已有数据（以前知识）支持PPQ的理由和科学说明要记录在工艺验证主计划中。所有用于支持PPQ的以前知识和阶段一的数据都必须可检索、可追踪、确认过、使用科学的实践产生的。
Figure 4.3.1-1 illustrates the relationship of the amount of knowledge to Stage 1 and 2 activities. Where there is greater prior knowledge or process design for a new product or process, PPQ studies may be decreased. Less prior knowledge will require more Stage 1 and/or PPQ data.
图4.3.1-1显示了阶段1和2的行动与知识量的关系。对于一个新的产品或工艺，以前的知识或工艺设计越多，PPQ研究可以降低。已有的知识越少，就需要更多的阶段1和/或PPQ数据。
Figure 4.3.1-1 Relationship of Prior Knowledge to the Amount of PPQ Data Required
图4.3.1-1 已有知识与要求的PPQ数据量的关系
Some examples of cases where prior knowledge may be useful to for PPQ include:
先验知识对PPQ有用的一些例子包括：
· Setting of acceptance criteria in PPQ studies: For example, bioburden and endotoxin in-process acceptance criteria in cases where facility history and limits for other processes can be applied to similar processes that employ the same facility and equipment. (Assumes the limits for the previous product are appropriate for the quality of the new product.)
PPQ研究中可接受标准的设定：例如，生物负荷和内毒素中控可接受标准的设定, 若其他工艺的限度和设施历史可被应用于使用相同设施和设备的相似产品。（假设前一产品的限度对新产品的质量是适当的。）
· Use of data from other product PPQ supportive studies: For example, in platform purification operations where same or similar buffer formulations will be used in the same vessels, buffer hold studies already performed for a different product can be used to support the PPQ for buffers used for the
new product.
使用其他产品的PPQ支持性研究数据：例如，在平台纯化操作中，相同或相似的缓冲液配方将用于相同缓冲容器中，对另一个不同的产品已进行的缓冲液贮存研究可以用于支持将用于新产品的缓冲液的PPQ研究。
· Using prior experience on similar processes: In non-sterile solid and liquid dosage manufacturing, such as granulating and film coating solution preparations, or bulk solution mixing and filling, prior experience with similar solutions or filling equipment may be applied to justify the number of PPQ
batches for those unit operations.Past knowledge of common excipients, such as fillers, binders, disintegrants, lubricants, and preservatives in the formulation and process is also an important factor.
使用相似工艺的先前的经验：在非无菌的固体或液体制剂生产中，例如制粒和薄膜包衣溶液的制备，药液混合或灌装，可以应用相似溶液或灌装设备的先前的经验来合理说明验证这些单元操作的PPQ 的批次数目。。通用辅料的过去的知识也是一个重要的因素，例如处方和工艺中的填料、粘合剂、崩解剂、润滑油和防腐剂。
Use of Stage 1 Data for PPQ
第1 阶段的数据用于PPQ
Processes and products for which there is little or no prior knowledge may require a greater emphasis on Stage 1 and PPQ activities to demonstrate an acceptable level of confidence in the process control strategy. Data from Stage 1 process characterization studies and clinical manufacturing are generally used to support the establishment of the control strategy for new products, as discussed in Section 3.0. Stage 1 data may be used to support PPQ if sufficient scientific evidence for its use is available. At a minimum, the studies claimed to support PPQ should represent the commercial manufacturing scale (e.g., be scale independent) or derived from qualified small-scale model(s) proven to represent the full-scale process. In some cases, data from clinical manufacturing batches may be used in conjunction with that gathered during PPQ to increase the amount of data that can be used to achieve an acceptable level of confidence in the process. Some examples of the use of Stage 1 data to support the PPQ include (see Section 7.1 for details):
对于仅有极少或没有已有知识的工艺和产品，可能要求更强调第1 阶段和PPQ 活动来证明工艺控制策略的可接受的置信水平。如第3.0 节所讨论，通常可以用第1 阶段工艺特性研究和临床用样品生产的数据来支持新产品控制策略的确定。第一阶段的数据可被用来支持PPQ，如果其使用有充分的科学证据。声明支持PPQ 的研究至少应代表商业生产规模（例如，应是规模独立的）或是来自已证明代表全规模工艺的经过确认的小规模模型。在某些情况下，可以联合使用临床用样品生产批次的数据与PPQ 期间收集的数据，以增加用于实现工艺的可接受的置信水平的数据的数量。使用第一阶段数据来支持PPQ 的一些例子包括（有关详细信息，请参见第7.1）：
· Large molecule example
大分子的例子
· Past experiences in clinical, and stability, and pilot batch manufacturing. Process evaluation batches help determine the amount of PPQ data. For example, in an oral solid dosage form of multiple strengths, at least 8 Stage 1 batches with the same commercial formulation were from clinical supply manufacturing, stability, pilot, process evaluation/design, and plant demonstration batches. The firm had extensive experience with the components, equipment, and unit operations for the dosage form: wet granulation, fluid-bed drying, milling, blending, compression, and film coating. These 8-plus batches played instrumental roles in the justification of the number of PPQ batches.
临床、稳定性和中试批生产的过去的经验。工艺评估批次有助于确定PPQ数据的数量。例如，多规格的口服固体制剂，至少8批具有相同处方的第1阶段的批次是来自于临床试验样品生产、稳定性、中试、工艺评估/设计和工厂实证批次。公司有关于组份、设备和该剂型单元操作（湿法制粒、流化床干燥、粉碎、混合、压片和包衣）的丰富经验。这8+批次对证明PPQ批数合理性有至
关重要的作用。
In some cases, Stage 1 data that supports PPQ may be supported in some cases by adding stricter testing for a defined number of batches to confirm the results obtained in the Stage 1 studies and the PPQ batches. For example, small-scale column lifetime studies may be used to support column reuse limits. These are then confirmed with a heightened level of impurity monitoring until the reuse period has been reached at full scale.
在某些情况下，可通过对规定的批数增加更为严格的检验来支持用于支持PPQ 的第1 阶段的数据来证实第1 阶段研究和PPQ 批次中获得的结果。例如，可用小规模的柱寿命研究来支持柱重复使用的限度。可在之后通过加强杂质监测来证实，直到重复使用时间达到全量。
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