英国药监局OOS翻译 - 图文(4)

Phase III Investigation步骤lll调查

? If the batch is rejected there still needs to be an investigation. 即便该批产品拒绝放行，仍然需要调查。 To determine:

– if other batches or products are affected.

– identification and implementation of corrective and preventative action. 决定：

- 是否其他批次或产品受到影响？ - CAPA的启动实施

Phase II Investigation

Conducted when the phase I investigations did not reveal an assignable laboratory error. Phase II investigations are driven by written and approved instructions against hypothesis. Prior to further testing a manufacturing investigation should be started to determine whether there was a possible manufacturing root cause. 如果步骤l调查没有找到明确的实验室差错，需要开展步骤ll调查。步骤ll调查应按根据假设制定的书面批准的方案开展。在开展进一步实验之前，生产调查应启动，以确定是否根本原因在生产上。

? If not already notified the contract giver/MAH/QP (in accordance with the responsibilities in the TA) should be notified along with production and QA if a manufacturing site. 在一个生产基地，如果还没有通知合同供应商/药品文号持有者/质量受权人（遵循TA规定的职责），应该连同生产及QA一并通知。

? It is important when considering performing additional testing that it is

performed using a predefined retesting plan to include retests performed by an analyst other than the one who performed the original test. A second analyst performing a retest should be at least as experienced and qualified in the method as the original analyst.

当考虑开展附加试验时非常重要的一点是，应由不同于原试验人员的另外的试验人员运用预先制定的再试验计划开展再试验。再试验人员的对该试验的经验和资质至少与原试验人员等同。

? If the investigation determines analyst error all analysis using the same technique performed by the concerned analyst should be reviewed. 如果调查确定为分析错误，那么使用同一方法开展的相关分析都应该回顾分析。

Phase II Investigation - Definitions

? Hypothesis/Investigative Testing –假设/调查试验

Is testing performed to help confirm or discount a possible root cause i.e what might have happened that can be tested:- for example it may include further testing regarding sample filtration, sonication /extraction; and potential equipment failures etc. Multiple hypothesis can be explored.

开展的试验能够帮助证实或者缩小根本原因的可能范围，也就是说，可能发生的事情能够被试验得出： 例如 可能包括更多的试验关于样品过滤、超声、提取；和潜在的设备故障等等。可以进行多个假设。 ? Re-Test –复检

Performing the test over again using material from the original sample

composite, if it has not been compromised and/or is still available. If not, a new sample will be used. 实验应再次使用原样品处理后的样品，如果它还没有被破坏而且还有效。不若不是，应使用新样品。

? Re-sample –重新取样

A new sample from the original container where possible, required in the event of insufficient material remaining from original sample composite or proven issue with original sample integrity. 尽可能从原样品容器中取新样品，当原样品的处理样品不足或者证实使用完整原始样品有问题时

? Most probable cause –最可能原因

Scientifically justified determination that the result appears to be laboratory error.

应科学系统的合情合理的决定是否因实验室错误导致OOS结果的出现。

Phase II Investigation - Unknown Cause / No Assignable Cause

步骤ll调查-未知原因/不确认的原因

Hypothesis Testing (Applicable to Phase Ia and Phase II):假设试验（步骤la和ll都适用）

? Should be started as part of Phase Ia and continue into Phase II if no assignable cause found.

如未发现明确的原因，应开始假设试验作为步骤1a的一部分，持续到步骤ll。 ? Description of the testing should be written, and then approved by

QA/Contract Giver/QA equivalent prior to initiating investigational testing. The requirements of investigational testing listed below: 在初始调查试验开始之前，应书面制定试验方案并经QA/合同供应商/具有QA职责的人的批准。调查实验要求如下： ? The description must fully document

– The hypothesis to the test the root cause being investigated. – What samples will be tested.

– The exact execution of the testing. – How the data will be evaluated 必须全面记录 - 为调查根本原因对试验的假设 - 检验什么样品 - 试验的准确开展 - 数据如何评估

? This Hypothesis testing may continue from the re-measurement of the original preparations. 假设试验可能从原始准备样品的复检开始。

? Investigational testing may not be used to replace an original suspect

analytical results. It may only be used to confirm or discount a probable cause. 调查试验不得用于替换原始怀疑的分析结果，它仅用于证实或缩小可能原因的范围。

If no assignable cause that could explain the results can be identified during the manufacturing investigation or the assay failure investigation retesting may be considered. Part of the investigation may involve retesting a portion of the original sample. 如果在生产调查或者分析失败调查中未能找到确切原因解释OOS结果，应考虑复检，调查的一部分可能包括一份原始样品的复检。

Retesting:复检

– Performed on the original sample not a different sample. 使用原始样品而不是另一份样品。