Selecting Swab Sampling Sites

beiwei5du

August 2002 Selecting Swab Sampling Sites
If sampling is designed to identify potential residues on cleaned equipment surfaces that might be transferredto the next manufactured batch, then it is necessary to select swab sample sites that can appropriately providethat information. This Cleaning Memo will cover selection of sampling sites for swab sampling (next month’swill cover an equivalent subject for rinse sampling).
There are generally five types of sampling sites (or sampling locations) that can be considered for cleaningvalidation protocols. They are:
1. Most difficult to clean locations: This is one type of a “worst case” location. Certain locations in themanufacturing equipment may be more difficult to clean, and therefore more likely to show residues first ifcleaning is inadequate. For example, if a lower than specified concentration of cleaning agent were to beused for cleaning, certain locations may still be acceptably clean, but there might be other locations (themost-difficult-to-clean locations) where residues are at unacceptable levels.
How does one select these locations? They can be selected based on good scientific (typically engineering)judgment. For example, any junction of two materials is probably more difficult to clean than a flatexpanse of one material. Another example might be the underside of the lip at the top of a vessel. A secondmethod of selecting these locations is prior experience. This prior experience may be anecdotal (thecleaning operators tell you the bottom of the agitator blade is always most difficult to clean). Priorexperience may also include information one learns from prequalification studies either that resulted in afailure or that had been designed (by making them less stringent) to identify the “first-to-fail” locations.
2. Locations that are likely to produce non-uniform contamination of the next batch: This is also a worstcase. The non-uniformity referred to is NOT non-uniform contamination of the process equipment prior tocleaning; rather it deals with the possibility that with certain equipment surfaces, residues on those surfacesmay preferentially transfer to only a limited portion of the next batch. This may occurs on items such asfilling needles and discharge chutes.
3. Representative functional locations: These are not necessarily worst-case locations. However, it isprudent to select “representative” functional locations in the equipment for sampling. This might include,for example, vessel sidewalls, vessel dome or lid, ports, valves, and agitator blades. At least one samplefrom each representative functional location should be considered. This can be particularly helpful inaddressing any cleaning validation failures.
4. Representative materials of construction: These are also not necessarily worst-case locations. However,it is prudent to select different materials that are present in the equipment, such as stainless steel, glass,and/or various plastics or elastomers.
5. Most likely to be recontaminated locations: This only applies to the cleaned equipment hold time(CEHT) studies. In sampling at the end of the "storage” or “holding” time of cleaned equipment, oneshould consider how the equipment can become recontaminated, and where that contamination is most likely to be. These sites are not necessarily the most-difficult-to-clean sites (as given in case #1 above).
Note that in many cases certain categories may overlap. For example, an agitator blade may represent both a“most-difficult-to-clean” location and a representative functional location.
While the specific swab sampling locations should be specified in the cleaning validation protocol, it ispreferable to have a separate document justifying the selection of those specific swab sampling locations forthat protocol or for a given piece of equipment.
This Cleaning Memo is designed to stimulate thought on the proper selection of swab sampling sites forpharmaceutical cleaning validation protocols. It is the responsibility of each facility to select sample sites thatprovide appropriate information in determining the cleanliness of the cleaned equipment.

beiwei5du

August 2002
Selecting Swab Sampling Sites (擦拭取样点选取）
If sampling is designed to identify potential residues on cleaned equipment surfaces that might be transferred to the next manufactured batch, then it is necessary to select swab sample sites that can appropriately provide that information（取样点的代表性，能提供足够的潜在残留物信息）. This Cleaning Memo will cover selection of sampling sites for swab sampling (next month’swill cover an equivalent subject for rinse sampling)（该清洗备忘录介绍了擦拭取样点的选取）.
There are generally five types of sampling sites (or sampling locations) that can be considered for cleaningvalidation protocols.
（一般情况下以下的的物种取样点类型应该在清洗验证方案中考虑）
They are:
1. Most difficult to clean locations: （最难清洗点）This is one type of a “worst case” location. Certain locations in the manufacturing equipment may be more difficult to clean, and therefore more likely to show residues first if cleaning is inadequate. For example, if a lower than specified concentration of cleaning agent were to be used for cleaning, certain locations may still be acceptably clean, but there might be other locations (the most-difficult-to-clean locations) where residues are at unacceptable levels. （即在出现清洗不充分的情况下，最难清洗点是最有可能存在清洗残留物的地方）
How does one select these locations? They can be selected based on good scientific (typically engineering)judgment. For example, any junction of two materials is probably more difficult to clean than a flat expanse of one material. Another example might be the underside of the lip at the top of a vessel. A second method of selecting these locations is prior experience. This prior experience may be anecdotal (the cleaning operators tell you the bottom of the agitator blade is always most difficult to clean). Prior experience may also include information one learns from prequalification studies either that resulted in a failure or that had been designed (by making them less stringent) to identify the “first-to-fail” locations. （关于“最难清洗点”的选取，一般是基于科学的判断（比如工程设计）或者以前的经验两个方面。所以关于“最难清洗点”的判断，使用FMEA并不合适，因为FMEA是基于假设失败模式分析而进行控制策略的制定，而并不适用于“最难清洗点”的选取，反而针对于“最难清洗点”的选取，基于一定的工程设计判断（简单的理由说明），以及相应的员工清洗问卷调查，反而更实际以及更合理）
2. Locations that are likely to produce non-uniform contamination of the next batch:（最有可能造成下一批次不均匀污染的设备点） This is also a worstcase. The non-uniformity referred to is NOT non-uniform contamination of the process equipment prior to cleaning; rather it deals with the possibility that with certain equipment surfaces, residues on those surfaces may preferentially transfer to only a limited portion of the next batch. This may occurs on items such asfilling needles and discharge chutes. （该“最有可能造成下一批次不均匀污染的设备点”并不是指清洗前不均匀污染的工艺设备点，而是指可能造成下一批不均污染的设备点，比如干燥器的出料口，注射剂灌装点等等，很可能在前面收料或灌装包装单位中造成污染，所以一般也会选取这些点为擦拭取样）
3. Representative functional locations:（代表性的功能位置） These are not necessarily worst-case locations. However, it is prudent to select “representative” functional locations in the equipment for sampling. This might include,for example, vessel sidewalls, vessel dome or lid, ports, valves, and agitator blades. At least one sample from each representative functional location should be considered. This can be particularly helpful in addressing any cleaning validation failures.（这些点不一定是worst case点，但是必须谨慎选取这些代表性的设备的功能位置作为擦拭取样点。比如，这些包括侧壁，釜顶，盖，进料口，阀门和搅拌桨。至少每一类的代表性功能位置做一个擦拭取样，这些对于调查解决清洗验证失败特别有用）
4. Representative materials of construction:（代表性的设备材质） These are also not necessarily worst-case locations. However,it is prudent to select different materials that are present in the equipment, such as stainless steel, glass,and/or various plastics or elastomers. （这些不一定必须是worst case点，但是，必须谨慎在设备中选取不同材质，比如不锈钢，搪玻璃，各种塑料和橡胶材质）
5. Most likely to be recontaminated locations:（最有可能被再次污染的点） This only applies to the cleaned equipment hold time(CEHT) studies. In sampling at the end of the "storage” or “holding” time of cleaned equipment, one should consider how the equipment can become recontaminated, and where that contamination is most likely to be. These sites are not necessarily the most-difficult-to-clean sites (as given in case #1 above). （这一点仅仅用于清洁设备的CHT时间的研究，在（清洁验证CHT验证中）在清洁设备的储存结束点进行取样，应该考虑到相应的设备通过什么方式会被二次污染，二次污染点最有可能在哪里，这些取样点不需要是最难清洗点。所以在清洁后保存时间CHT研究的时候，保存时间点的取样点的选取应该考虑到这些点！！）
Note that in many cases certain categories may overlap. For example, an agitator blade may represent both a“most-difficult-to-clean” location and a representative functional location.
While the specific swab sampling locations should be specified in the cleaning validation protocol, it is preferable to have a separate document justifying the selection of those specific swab sampling locations for that protocol or for a given piece of equipment. （最好是将“擦拭取样点的选取”独立于清洁方案并且针对于特定的设备进行选取点的理由说明。比如针对于反应釜，可以根据上面五点制定相应的评估，以用于反应釜的“擦拭取样点”选取支持）

This Cleaning Memo is designed to stimulate thought on the proper selection of swab sampling sites forpharmaceutical cleaning validation protocols. It is the responsibility of each facility to select sample sites thatprovide appropriate information in determining the cleanliness of the cleaned equipment.

beiwei5du

不知道到大家的swab sampling locations/sites是如何进行的呢？？@谢大侠来了 @windy

beiwei5du

关于擦拭取样点一定要经过风险评估吗？？像这种是否可以通过工程和以前清洗经验进行确定即可（比如使用问卷调查和PID图工程图上标注即可）？？？？

wang82888

最好加一个Risk assessment

beiwei5du

wang82888 发表于 2016-11-1 14:58
最好加一个Risk assessment

你们是如何进行的呢？？？

小金库

感谢分享。