Procedure for Sampling in Process Validation

Sampling plays a major role in achieving the accurate results of the analysis. Sampling plan and procedure must be defined in validation protocols and training should be provided to the concerned staff before the validation activity starts.

Samples are representative of the whole batch. So it should be homogenous and should be taken properly from appropriate locations. Blend samples should be handled and weigh carefully because segregation may occur during weighing and transpiration. 

Sample quantity should not be more than the required and whole mass of each sample should be used in the analysis.

Sampling for Blend:

Blends are tested for their homogeneity. Homogeneity of the blend is critical for the quality of the final product. The sample should be taken from at least 10 locations in the blender. Sampling location should be selected according to the difficulty of the blending. 

Areas of poor blending must be covered in sampling. Corners and discharge point must have sampling location. Blender geometry should be taken into consideration during the sampling of the blender. 

Following are the sampling locations for octagonal blender.

1^st Sampling Set: A=Left-Top (Left Arm)

2^nd Sampling Set: B=Back-Top, C=Back-Middle

3^rd Sampling Set: D=Center-Top, E= Center-Middle Top, F= Center-Bottom, G=Discharge-Port

4^th Sampling Set: H= Front-Top, I=Front-Bottom

5^th Sampling Set: J= Right-Top (Right Arm)

Blend uniformity samples should be taken directly from the blender just before unloading the blend. If it is not possible to perform sampling from blender then the sample may be taken from the container after unloading. Three samples should be taken from each sampling location.

Acceptance criteria for blend uniformity = RSD ≤ 5%.

Related: Sampling of In-process Samples

Sampling for Finished Product: During the packing/filling sample should be taken at following intervals.

A) Beginning: Sample should be taken at the beginning of the packing/filling process. First manufactured units should be collected as a sample.

B) Middle: During the whole process samples should be collected to prepare one sample representing the whole process.

C) End: Very last produced units should be collected as a sample.

Additionally, if any critical event occurs during the packing/filling process which may affect the product quality e.g. any breakdown in packing/filling machine, the sample should be taken when the process starts after breakdown.

FDA’s Guidance on Process Validation

Also see: Process Validation Protocol

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