发布时间 : 星期二 文章英国药监局OOS翻译 - 图文更新完毕开始阅读2d35954710661ed9ad51f388
Phase Ib Investigation – Definitions定义
Specification –标准
A specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which a drug substance, drug product or materials at other stages of its manufacture should conform to be considered acceptable for its intended use. ―Conformance to specification‖ means that the drug substance and drug product, when tested according to the listed analytical procedures, will meet the acceptance criteria. Specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval.
标准被定义为一组测试，参照分析程序，及适当的接受条件，这些标准应为数字限度、范围或这一组测试描述的其他条件。建立的这套在生产过程各阶段的药物、药品或材料的标准，如果达到，应当被认为就符合其预定用途。“符合标准”意味着药物以及药品，当按照这套分析程序检验，达到了可接受条件。标准是判定性的质量标准，它是有生产厂家提出并证实，由法规机构作为批准条件颁发的。
? Regulatory Approved Specification –法定标准
Specifications for release testing. If no release specifications have been established then the internal specification becomes the release specification. 放行试验标准。如果没有放行标准被建立，那么中间控制标准即为放行标准。 ? Acceptance Criteria –可接受标准
Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures which the drug substance or drug product or materials at other stages of their manufacture should meet. 生产各过程的药物、药品或物料应当符合限度、范围或者分析过程结果的其他合适的可接受方式。 ? Internal Specification –中间标准
Are also action limits within regulatory specifications. 法定限度内的行动线。
Assignable Cause –明确原因
An identified reason for obtaining an OOS or berrant/anomalous result. 出现OOS或者异常结果的被确定的原因
? No Assignable Cause –非明确原因
When no reason could be identified.无法确定的原因 ? Invalidated test –无效实验
A test is considered invalid when the investigation has determined the assignable cause. 经调查确定可指明原因，试验被认为无效。 ? Reportable result –可报告结果
Is the final analytical result. This result is appropriately defined in the written approved test method and derived from one full execution of that method,
starting from the original sample. 为最终分析结果。使用书面的批准方法适当的明确并且从这一方法完整执行后得到的结果，此结果从原始样品的检测结果。 ? Warning Level or Trend excursions –警戒水平或者趋势偏离
If two or more consecutive samples exceed warning (alert), or if an increasing level of counts, or same organisms identified, over a short period was identified consideration should be given to treat the results as action level excursions. 如果两个或者更多的连续取样样品超出警戒，或者如果出现数量水平的持续增加，或者相同的微生物被鉴定出来，极短时间得到鉴定，应该被认作行动水平偏离导致的结果。
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。
Investigation by Analyst and Supervisor
分析人及主管调查
Phase Ib Investigation – Initial Investigation conducted by the analyst and supervisor using the Laboratory Investigation Checklist 1b步骤调查-由分析人及主管使用实验室调查清单开展的最初调差。
? Contact Production/Contract Giver/QP/MAH as appropriate 视情况联系生产、供应商、质量受权人、药品批准文号持有者。
? For microbiological analysis where possible once a suspect result has been identified ensure all items related to the test failure are retained such as other environmental plates, dilutions, ampoules/vials of product, temperature data, autopipettes, reagents – growth media. No implicated test environmental plates should
be destroyed until the investigation has been completed. 对于微生物分析实验，一旦发现可以结果，应确保与本失败实验相关的所有物品得到保存，例如环境监测平皿、稀释液、产品安瓿或西林瓶、温度数据、自动吸样器、试剂-培养基。试验相关的环境监测平皿不得销毁，直到调查完成。
? The Analyst and Supervisor investigation should be restricted to data / equipment / analysis review only 分析人及主管调查应仅限于数据、仪器、分析过程回顾。
? On completion of the Analyst and Supervisor investigation
re-measurement can start once the hypothesis plan is documented and is only to support the investigation testing. 分析人及主管调查完成，一旦假设方案记录下来并且只支持调查试验，那么就可以再开始试验。
? This initial hypothesis testing can include the original working stock
solutions but should not include another preparation from the original sample (see: re-testing) 这个最初的假设试验从原始工作储备溶液开始，但是不包括从原始样品开始。
The checklist may not be all-inclusive, but should be a good guideline to cover the pertinent areas that need to be covered in any laboratory investigation:- 检查清单不可能非常详尽，但是应该是一个良好的指导，包括了在任何实验室调查中覆盖的相关方面。 - Correct test methodology followed e.g.. Version number.
是否遵循的正确的实验方法，例如所用的文件版本号
- Correct sample(s) taken/tested (check labels was it taken from correct place). 是否使用正确的样品或样品处理（检查样品标签，确认从正确的地方得到的样品）
- Sample Integrity maintained, correct container and chain of custody (was there an unusual event or problem). 样品保存的完好性，正确的容器及保管链（是否存在异常事件或问题？） - How were sample containers stored prior to use. 样品使用之前，样品容器如何存放？
- Correct sampling procedure followed e.g. version number. 是否遵循正确的取样程序，例如文件版本号。
- Assessment of the possibility that the sample contamination has occurred during the testing/ re-testing procedure (e.g. sample left open to air or unattended). 评估在实验或复检过程中样品污染的可能性（例如样品非受控开口存放）
- All equipment used in the testing is within calibration date. 所有使用的仪器均在校验期内。
- Review equipment log books. 回顾审核仪器使用维护记录
- Appropriate standards used in the analysis. 分析过程中是否使用合适的标准品。
- Standard(s) and/or control(s) performed as expected. 标准品或内控品的使用是否合规
- System suitability conditions met (those before analysis and during analysis). 是否达到系统适用性（那些分析之前的或者分析过程中的） - Correct and clean glassware used. 是否使用正确的、洁净的玻璃器皿？
- Correct pipette / volumetric flasks volumes used. 是否使用正确量程的吸管量瓶？
- Correct specification applied. 是否使用正确的说明书。
-Media/Reagents prepared according to procedure. 培养基、试剂是否按程序准备。
? Items were within expiry date 各试验物料是否在有效期内。
? A visual examination (solid and solution) reveals normal or abnormal appearance 是否肉眼检查（液体或固体）发现正常或非正常外观？ - Data acceptance criteria met 是否达到验收标准?