Issue with cleaning between two "products"

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Hi all, need your opinions. First some background, I work for a solid oral dosage pharma company making a bi-layer tablet. One layer is formulated to dissolve instantly and the other is formulated to dissolve slowly. In one formulation both layers contain active ingredient X and a second ingredient Y, and of course each layer contains different excipients.

My problem: manufacturing wants to granulate the instant dissolve portion of the tablet followed by granulating the longer acting portion of the tablet without a complete cleaning of the mixer. Currently, the mixer is cleaned thoroughly at the end of the run and then other granulations may be processed in the mixer. Now they say because the actives (X and Y) are the same in both types of granulation and the risk of the excipients being carried over into the finished product is nil (since the finished tablet contains all ingredients from both types of granulations), there is no need to do a thorough clean between the two types of granulations.

I think they are two seperate products and a thorough clean is necessary, regardless of the fact that all ingredients are found in the finished tablet.

Please give me your opinions.

Thanks

Gray61

2

Dear Gray61
The major concern for cleaning val is cross contamination from different products. In your case although they are different formulations, but the actives are same. There aren’t cross contamination issue. Visible cleaning may be good enough.

3

Dear Gray 61,
I agree to b0b comments.
Visual cleaning will be sufficient

4

In case of issue between two product having same active ingredient, thorough cleaning is just waste of time and money with no advantages.

But it is also better to have manufacturing the product with lower strength first and then only the product with higher strength. In the latter case cleaning is required.

5

Dear Gray61,

I agree in that the cross contamination with active between the two layers is no issue. The only concern would be a cross contamination with an excipient from one layer that could affect the dissolution in the other (surfactants, matrix building excipients, simethicone, etc.). Nevertheless, even with only a gross cleaning this should be no issue.

Best regards

Alfred