关于清洁验证中淋洗水法回收率的验证

swylove1987

清洁验证中淋洗水法的回收率怎么验证？谁有相关资料提供一下，谢谢

Sword

喷，冲，检，算

快活王

PDA TR29中有这部分资料，可以自行查阅，该文件在坛里里有

药窕淑女

这一块是不好做
PDA TR 29 6.5.3讲的还可以，可以参考

swylove1987

非常感谢楼上几位的回答

beiwei5du

快活王 发表于 2015-4-10 13:16
PDA TR29中有这部分资料，可以自行查阅，该文件在坛里里有

但是对于淋洗取样的回收率达到多少可以被接受呢？？PDA TR29中也未提及（但提及到swab sampling recovery)???@hongwei2000

scino

beiwei5du 发表于 2015-10-9 18:20
但是对于淋洗取样的回收率达到多少可以被接受呢？？PDA TR29中也未提及（但提及到swab sampling recovery ...

一般是80%。擦拭50%

beiwei5du

scino 发表于 2015-10-10 13:45
一般是80%。擦拭50%

该数据是出自哪里呢？？实际有测？？？

快活王

beiwei5du 发表于 2015-10-9 18:20
但是对于淋洗取样的回收率达到多少可以被接受呢？？PDA TR29中也未提及（但提及到swab sampling recovery ...

这个在PDA技术报告中也有描述，一般是要求50%以上，要是低于50%的话，需要改进取样方法或者说明理由。简单来说，回收率越低，越不准确，其他的也没有什么。

beiwei5du

快活王 发表于 2015-10-10 15:24
这个在PDA技术报告中也有描述，一般是要求50%以上，要是低于50%的话，需要改进取样方法或者说明理由。简 ...

是否能贴原文呢？？我没有找到呢！你那个应该是针对于swab sampling recovery的说明。

beiwei5du

但是在APIC CLEANING VALIDATION中确实有如下：
In a worst case approach, the amount of th e residue in the equipment can be assumed to be equal to the amount determined by an alysis of the rinse sample. This can be supported by rinse studies that show a strong decay of a residue in a piece of equipment.
但是这个也是在bracketing(分组）条件的，采用worst case进行清洁验证的前提下，才进行rinse studies以证实strong residue decay in equipment。那么是不是说明在一般的清洁验证上就不进行rinse sampling recovery测定？？或者如果你采用的rinse都是对residue是良溶剂或热溶剂，一般都会达到90%以上的回收率，那么就没有必要再进行回收率测定？？？？？？？@windy

windy

beiwei5du 发表于 2015-10-11 13:59
但是在APIC CLEANING VALIDATION中确实有如下：
In a worst case approach, the amount of th e residue i ...

有必要的，应该考虑分析方法和清洁程序对回收率的影响

beiwei5du

windy 发表于 2015-10-12 11:23
有必要的，应该考虑分析方法和清洁程序对回收率的影响

那么法规对于rinse sampling recovery有接受范围和RSD要求么？？？淋洗回收率重新性（RSD)是否良好呢？？

windy

beiwei5du 发表于 2015-10-12 12:04
那么法规对于rinse sampling recovery有接受范围和RSD要求么？？？淋洗回收率重新性（RSD)是否良好呢？？

建议Rinse>80%，Swab>50%，RSD可以参考APIC/PDA TR29。淋洗法回收率重现性良好

beiwei5du

选自：http://www.askaboutgmp.com/forum ... 1852-Rinse-Recovery

Rinse Recovery Study Procedure

There are few ways you can perform rinse recovery studies. Following are the methods commonly used in industry for performing rinse recovery studies.

STEP I: Select an appropriate solvent (usually organic solvent) to dissolve the target residue under study. In order to expedite drying time and allow an even distribution of the target residue on the surface being studied, the residue stock solution should be made up in suitable organic solvent (e.g. alcohol, chloroform, acetone).

STEP II: Prepare the residue stock solution by dissolving known amount of residue in the solvent.

STEP III: Select the material (e.g. stainless steel, glass, rubber etc.) for conducting recovery studies. Obtain coupons or containers (of appropriate dimensions) made up of same material as the production equipment. Usually 25 cm2 coupons are used for recovery studies, you may select coupons with larger surface area also.

STEP IV: Determine type and volume of rinse solvent. Rinse solvent selected for recovery studies should be the same as the one used for actual rinse sampling. Determine what volume of the rinse solvent would cover the selected surface area (e.g. 5 x 5 = 25 cm2) in actual sampling condition. Make sure that the ratio of rinse solvent to surface area should not be more than the expected ratio under actual rinse sampling conditions. For example, in actual condition if you want to collect rinse sample from an equipment with a surface area of 1000 cm2 using 10 L of rinse solvent then the ratio of volume of the rinse solvent to surface area would be 10 ml per cm2 (10,000 ml / 1000 cm2). This means that you have to use 250 ml of rinse solvent in recovery studies to collect rinse sample from 25 cm2 coupons. Another important factor that should be considered is the temperature of the solvent for the recovery study, it should be the same as that of the actual rinse sampling solvent.

STEP V: Spike the coupon or container with an aliquot of stock solution yielding a concentration equal to 50%, 100%, and 200% of the calculated MACO per cm2 of surface area for the target residue being studied. This can be done by pouring/applying appropriate volume of residue stock solution using a pipette or syringe (as highlighted by Alfred). If the concentration of stock solution is 50 μg/ml and the MACO calculated by usual method is 50 μg/25 cm2, then you need to apply 0.5 ml, 1.0 ml and 2.0 ml to obtain 50%, 100% and 200% of MACO/25 cm2. Spiking residue at three or more concentrations is generally done to study the linearity of the method and is not a regulatory requirement. In case, you are interested in spiking only one concentration then spike residue at only 100% level.

STEP VI: Allow surface to air dry. Repeat each concentration 3 times. “Control” must be included in the study in order to establish a baseline. Note: it is important that all the solvent has evaporated from the surface prior to rinsing.

STEP VII: Conducting rinse sampling: Use any one of the following method to simulate rinsing:

Method A: Position the spiked coupon over a beaker to collect the rinse-sampling solution, then carefully pipette the required volume of rinse solvent over the coupon making certain that all the surface area is contacted by the solvent, and finally let the solution collect in the beaker below.

Method B: Spike the bottom of beakers/containers (made up of selected material of construction) with residue, add a fixed volume of rinse solvent, and agitate. Collect the sample by transferring the rinsate to separate beaker or test tube.

Method C: Place the coupon in an appropriate amount of rinse sampling solvent into the bottom of a beaker and gently swirl for ~30 sec. The coupon and rinse solvent should be separated immediately to stop the dissolution process. (Note: Make sure the underside of the coupon should not come in contact with residue while spiking the residue onto the surface).

STEP VIII: After the simulated rinse sampling, collect the rinse sample and analyze for the target residue and compare with the amount spiked onto the coupon. Residue recovery is then calculated as follows:


% Recovery = (Amount detected / Amount spiked) x 100

Few other issues that are required to be considered include (but are not limited to):
A. Potential interferences
If the excipients can be suspected to interfere with rinse sampling/analytical testing, the spiking of the active should be performed in their presence.

B. Stability considerations
1. The time between actual cleaning and sampling from the surface and the shelf life of the rinse sample collected needs to be mimicked for the recovery studies.
2. The ageing effects should be investigated with respect to the actual rinse sampling conditions.

beiwei5du

快活王 发表于 2015-10-10 15:24
这个在PDA技术报告中也有描述，一般是要求50%以上，要是低于50%的话，需要改进取样方法或者说明理由。简 ...

The residue amount in the equipment  can be assumed to be equal to the amount of residue in the last wash or rinse solvent portion. The assumption is based on the worst case consideration t hat a further rinse (or any reaction) would not remove more than the same amount of residue present in the analysed rinse sample.选自《apic cleaning validation》 基于这个理解，淋洗液取样并计算carry-over的前提是其至少必须达到50%，所以在其计算carry-over过程中并不将这个回收率拿入计算！@scino

快活王

beiwei5du 发表于 2015-10-13 22:21
The residue amount in the equipment  can be assumed to be equal to the amount of residue in the la ...

不好意思，我记混了，是在擦拭法回收率中提到了50%的相关描述，但是我认为冲洗法的回收率应当同样复核他们的要求。详见PDA TR29中6.5.2部分，受公司电脑所限，无法上传截图，还请自行翻阅。