个人以为是要控制，当然锁定是其控制的一种具体的形式。

也就说通过控制来降低风险至合理水平。

至于具体的情况，如果方法稳定经过验证，仪器设备性能良好，操作规范，通常是具有较高的重现性的。如果出现了不可接受的情况，通常是需要调查确认的。

不因为仪器，色谱柱，流动相等它们不会说话而怪罪它们，本质上可能还是主要由人的因素引发的。

HPLC积分方法设定应该达到准确、科学、稳定的积分效果，如果达不到科学积分，可进行调整积分参数或手动积分，但两者均需要进行科学的论述和说明，手动积分应该限制并有批准授权程序进行，同时在第二人数据审核时进行涵盖包括审计追踪的审核。

法规和指南中并未明确规定必须锁定积分方法，锁定积分方法虽然规避了人员手动积分或者篡改色谱数据的风险，也同时给企业带来了很多的效率的降低，应该基于各企业的内部控制、色谱方法的稳定性、审核体系的完整性等；WHO色谱指南中相关的要求如下，可进行参考。

13. Peak integration

13.1 Peak areas in chromatograms should be accurately and consistently integrated in a scientifically sound manner.

13.2 Where possible, HPLC and GC instruments should be interfaced with computerized chromatographic data-capturing and processing systems that are capable of applying the integration parameters set, automatically and consistently.

13.3 To facilitate the accurate integration of chromatographic peaks, it is preferable that all of the peaks are fully separated. However, when quantitative data are to be obtained from unresolved peaks, the laboratory should have clear policies as to how such peaks should be integrated. This should include a description of the type of integration to be used, with a justification for its use, including, for example:

■ tangential skim;

■ exponential skim;

■ exponential curve fitting;

■ straight line skim;

■ front peak skim;

■ rear peak skim;

■ peak-to-valley ratio; and

■ valley height ratio.

13.4 Validated methods, specified chromatographic conditions and good chromatography practices should facilitate obtaining symmetrical peaks. Where atypical peak shapes are observed, these should be investigated and appropriate action taken.

1 3.5 Where manual integration has to be done, authorized procedures should be followed. Records should be maintained and include the authorization and justification for manual integration.

13.6 Using a procedure to integrate peak height or area by manually setting the baseline using chromatographic software should only be allowed in exceptional cases. Only trained, experienced users should be granted privileges to do so. Records and justification should be given when this procedure is followed.

13.7 Where smoothing is applied, the type of “filter” used and the extent of smoothing should be justified.

当然 需要锁定，锁定并不意味着不能改，而不是能随意改，修改积分方法应该由更高级别的人员来执行或通过审批后才能执行。

已经完成验证且比较成熟的方法建议锁定积分。但是应该有程序规定，当方法不合适时，可以进行调整。

任何问题都要结合实际来看，不能教条执行，反对本本主义，毛选建议看一下，这个很关键，任何教条执行都会是不合适。

没有锁定积分，但是SOP会规定什么情况下可以手动积分（受控，批准），不允许随意的手动积分

简单来说当样品检验方法已建立并经验证，则需锁定积分方法，以确保数据可靠性；另一方面，在方法开发及探索试验阶段，色谱条件尚未优化，此时需灵活调整积分方法，待条件优化后再固化积分方法。