Process Validation

GOOD VALIDATION PRACTICE (cGVP)
#1

We are manufacturing tablets with highly potent API i.e. 0.035 mg per tablet. Its a wet granulation process. After blending the BU result found satisfactory but after compression in a single rotary B tooling machine we found some of the tablets are not showing the presence of API in it i.e. zero peak.

What are the probabilities are there in compression so that API may detach from the ingredients in few cases & are not showing any peak in CU test of tablets ?

#2

Compression is a process where the blend mixture is formed into a tablet as per the capacities of the tools.
There is no technical evidence given in books or journals that loss of a API due to compression or during compression process unless you have sticking problems where loss of total blend takes place.
I strongly reccomend how you are sampling your Granulation blends and how robust is your blending process and what type of Blender you are using?

Foremost thing you have to do is look your blending cycles, blending validation documents and time of blending.
As the drug substance is too minute due to activity of this drug substance , any sticking during wet granulation might result in loss of API. Secondly how is your HAPI is added during your wet granulation process–what I mean to ask is do you have a Human intervention or is it automated process?

How robust and how sound is your bend validation process technically?

I request you to carry out a Scale-Down study. That means take a pilot batch and test your process.

Regards

#3

The API could have broken down by the effect of heat or moisture, you can recheck the parameters again

#4

Reem,
Thats a great reply you gave.
Yes there is every possibility.
If the drying temperature is higher than melting point of API it can cause such problems.

Regards

#5

it is my pleasure to be able to help

#6

Hi All,

World is full of Possibilities.

In the first sight, the case seems related to the un-even distribution of Active in Blend !!

You can utilize 5W-1H technique to identify the problem. Get the following answers

  1. Is the Blending Validation already in place with uniformity studies…
  2. Is the Compression machine have challenge studies during qualification…
  3. Process parameters already validated are you are going to do it first time…
  4. Split compression Individual testing in place or not !!
  5. Physical observations of process…before / After compression…
  6. Process chemistry… effect of temp / Pressure on active…
  7. Discussion with core team …believe me it is of great help…

Happy Reading !

#7

Don’t forget to check the analytcal part as well !!!

Not Only Mfg…always made defects…ooops !