Bracketing for process validation

Dear Forum,

I have to validate the same process for 3 strengths of the same product (the only difference is the quantity of API, compensated by the quantity of one of the excipient).
I have been told that bracketing could be used for process validation, only if strongly justified.

What kind of strong justification could be used (what does “strong” mean) ?
Is there any guideline for the use of bracketing during process validation (I only know the guideline ICH Q1D for stability studies) ?
Have you ever submitted such process validation to the FDA ?

Thank you for your help !

I can give an idea about few things how bracketing of validation is done as we have done.

In your case you have 3 different stregths of products and 2 different variants in excipients. This is how FDA will look into your product.

In such a case you need to consider validation of 2 batches with lowest concentration and highest concentration of API. I think that these 2 batches will also have change in concentration of excipients.

In such a case you need not perform 3 x3 bath validation.

You can actually take 2 batchs (Lowest and Highest concentration of API’s) 3 runs each.

Bracketing of concentrations may prove prudent in your case.
You must perform such study taking risk based approach.
If it is a parenteral product, there might be a variation in container sizes too. In such a case you can also bracket the media fills between Lowest container size and Highest container size.

Well the STONG JUSTIFICATION is needed why you skipped the batch validation of that particular concentration, how is your process is not different in mixing/blending/ sieving/compression etc when compared the above batches. How your size of equipment and operating conditions such as Temp, Pressure, air etc are just fall with in validated limited as earlier batchs.
The limits must be very tight and cleaning methodology too must be bracketed.

This was our experiece and we encountered only one time for a particular product which was soled in UK as a Vet product.It was 3 years back.



Good Evening !

Bracketing for process validation : This is a approach to utilize the beauty of Validation.

Well as Mr. Durga said Lower & Upper sizes of batch / strength needs to be validated, absolutely in agreement.
In addition to this the Key Point “Strong Justification” must be supported for rock hard background i.e. Risk Assessment

You can utilize the great tools of Risk assessment as defined in ICH Q-9, which is already accepted to FDA also.

What you need to be built in risk assessment is :

  1. Complete Process Comparision
  2. Flow Charts of Process
  3. Step wise elimination / Reduction of Validation Scope.
  4. Synthetic Scheme which shows there is no chemical change in these d/f batch sizes…and Moreover to all of this a solid conclusion which stats “ReQuIrEd CoNcLuSiOn”

Hopes it will help, if any other details required please.

Happy Reading !