翻译完稿 GUIDE TO INSPECTIONS OF PHARMACEUTICAL QUALITY CONT(8)

实验室极其重要的一项功能就是检验混料，在提高发现劣等产品批次的可能性方面，混料检验必不可少。不能因偏好于依赖对成品的检验而放弃对混料均匀度的检验，因为成品检验有其局限性。

One court has ruled that sample size influences ultimate blend test results and that the sample size should resemble the dosage size. Any other practice would blur differences in portions of the blend and defeat the object of the test. If a sample larger than the unit must be taken initially, aliquots which resemble the dosage size should be carefully removed for the test, retests, and reserve samples. Obviously, the initial larger sample should not be subjected to any additional mixing or manipulation prior to removing test aliquots as this may obscure non-homogeneity.

某法律规定，因取样量影响最终混料检验的结果，取样量应与制剂取样量相当。其他任何做法只会混淆混料各部分之间的区别，从而无法达到检验目的。如果样品的首次取样量必须大于使用的单位量，则应仔细取出与制剂取样量相当的等份用于检验、复检及留样。显然，最初的大用量样品在等份被取出前不易另行搅拌或处理，否则会掩盖样品的非均匀性。

Multiple individual blend uniformity samples taken from different areas cannot be composited. However when variation testing is not the object of assay testing, compositing is permitted.

用作混料均匀度测试的数个样品，如果采自不同区域，则相互之间不得混合，除非在以含量测定为目的而不是为了考察其差异性的情况下，才允许混合。

If firms sample product from sites other than the blender, they must demonstrate through validation that their sampling technique is

representative of all portions and concentrations of the blend. This means that the samples must be representative of those sites that might be problems; e.g. weak or hot spots in the blend.

如果药厂的样品不是取自混合器，则应通过验证证明其取样技术能反映混料各个部分和总体的特征。也就是说，这些样品必须能够代表生产中可能发生问题的位点，如混料中的薄弱点或过热点。

11. MICROBIOLOGICAL 微生物方面

The review of microbiological data on applicable dosage forms is best performed by the microbiologist (analyst). Data that should be reviewed include preservative effectiveness testing, bioburden data, and product specific microbiological testing and methods.

对制剂产品微生物学数据的审查最好由微生物学家(化验员)完成。应审查的数据包括防腐剂的有效性测试、生物负荷数据以及特定产品的微生物检验及其方法。

Review bioburden (before filtration and/or sterilization) from both an endotoxin and sterility perspective. For drug substance labs evaluate methods validation and raw data for sterility, endotoxin testing,

environmental monitoring, and filter and filtration validation. Also, evaluate the methods used to test and establish bioburdens.

从细菌内毒素与无菌性两方面审查过滤前和(或)灭菌前产品的生物负荷状况。对于原料药检验实验室，要评价其方法验证以及无菌性和细菌内毒素检验、环境监测、滤器及过滤方法验证的原始数据。此外，还要评价实验室检验及确定生物负荷量所采用的方法。

Refer to the Microbiological Inspection Guide for additional information concerning the inspection of microbiological laboratories.

参考《微生物学检验指南》，以便获取更多关于检查微生物实验室的资料。

12. SAMPLING

取样

Samples will be collected on pre-approval inspections. Follow the sampling guidelines in CP 7346.832, Part III, pages 5 and 6.

在药品审批前检查时采集样品。依照CP7346．832第三部分，第五、六页上关于取样的指导进行取样。

13. LABORATORY RECORDS AND DOCUMENTATION 实验室记录和文件

Review personal analytical notebooks kept by the analysts in the laboratory and compare them with the worksheets and general lab notebooks and records. Be prepared to examine all records and worksheets for accuracy and authenticity and to verify that raw data are retained to support the conclusions found in laboratory results.

审查化验员保存的实验室个人分析记录，并将其与工作单及总实验室记录比较。为厂准确与可靠起见，准备检查所有记录与工作单，核实确已保留下来的原始数据，以便保证从实验室结果中得出的结论。 Review laboratory logs for the sequence of analysis versus the sequence of manufacturing dates. Test dates should correspond to the dates when the sample should have been in the laboratory. If there is a computer data base, determine the protocols for making changes to the data. There should be an audit trail for changes to data.

参照生产日期的顺序审查实验室记录的分析顺序。检验的日期应与样品确实存在于实验室的日期相符合。如果使用电脑数据库，应确定改变数据的方案，对数据变更应建立跟踪审计程序。

We expect raw laboratory data to be maintained in bound, (not loose or scrap sheets of paper), books or on analytical sheets for which there is accountability, such as prenumbered sheets. For most of those

manufacturers which had duplicate sets of records or \

non-numbered loose sheets of paper were employed. Some companies use discs or tapes as raw data and for the storage of data. Such systems have also been accepted provided they have been defined (with raw data identified) and validated.

我们希望原始实验数据能成册保存(避免散乱或用零碎纸张记录)，或以书本、或以事先编号可以计数的化验单的形式保存。大多数生产企业复印的多套记录或“原始数据”中，不乏未标明页码的散纸片。一些公司使用磁盘或磁带记录并储存原始数据，只要表述明确(原始数据予以标明)，且经过验证，这样的系统是可以接受的。 -----------赖楷贤

Carefully examine and evaluate laboratory logs, worksheets and other records containing the raw data such as weighings, dilutions, the condition of instruments, and calculations.

仔细检查和评估实验室日志、工作记录以及其他一些包含原始数据的记录，如称重、稀释、仪器状态、计算等。 Note whether raw data are missing, if records have been rewritten, or if correction fluid has been used to conceal errors.

注意原始数据是否有缺失，记录是否被重写，或用涂改液来掩盖错误。Results should not be changed without explanation. 没有解释说明不能更改 …… 此处隐藏：4340字，全部文档内容请下载后查看。喜欢就下载吧 ……