Process validation (brackiting)

Hi every one !
I am new in process validation ,
I have do validation for mixing and filling line for parenteral products , we have a huge amount of new products to be lunched in the line.

all our products is solutions (no powders, no oily).
I am planning to do process validation for these products by martixing (bracketing) the products by it solubility or density. so I will do the process validation for only the products which comes as worst case !! (i.e insoluable , low dense …etc)
is this kind of validation allowed ?? If yes , what I should follow to do the bracketing ?? where I can found I guidelines for that so I can follow even to show for authority !

thanks a lot

Follow US Guideline (issued 2011) on process validation, Health Canada Guide #29, EMA (EU eudralex) on process validation.

As part of your ‘risk analysis’ you can evaluate specific gravity (density). Solubility is part of your development of the cleaning procedure.

Perform ‘dye’ tests on your compounding tank at demonstrate homogeneity using time, temperature, and rpm…

thanks boomer for your reply ,would you please describe briefly how to perform the dye test ??
is this test to demonstrate the critical area along with our tank which shows deviated area from the homogeneity??

thanks :slight_smile:

Review these slideshares!

In essence you’re demonstrating that your compounding tank is capable of making your drug product reliably and consistently. Obviously this applies to not only parenterals but also softgels (but not tablets).
Parameters include mixing time, temperature, density, concentration, mixing speed, type of shaft.

Deviations from homogeneity may be mitigated by increased mixing time or speed.

For Mixing:

Mixing can primariliy be a function of solubility - it sounds like all of your processes are water based? If so, then mixing might be boiled down to solubility, and amount of solute (what is being disolved).

Here is an easy equation: ranking = (solubility) / (amount to dissolve).

The higher the number, the easier it is to dissolve. This is because solubility is high, or amount to dissolve is low.

You could take the top 3 products, and test them in the lab (quick and cheap). Then you could take the top 1 product and test it in the field with a full process validation.

This of course assumes that the mixing equipment is the same. A change in mixing, might require a separate process validation (they are different processes and should be validated under a different process validation).

Overall make sure that all factors are accounted for. Affect of temperature on mixing, chemical reactions, etc.

For filling.

Viscosity is one of many primary things to look at. Fill weights, fill containers, etc, all should be a part of filling process validation. There might be some similar products which can be bracketed, but likely there are a bunch of presentations which are different enough that 1 single bracket approach won’t work.


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