Change batch size


(Ahmed Adel Ibrahim) #1

if we changed batch size for sterile or non sterile product , then its need to do stability study ??


(Sajjad Ahmad) #2

to change batch size validation is required.?


(Sajjad Ahmad) #3

Changes in Batch Size

Changes in the size of a batch from pilot scale to small or large production batches after approval of a new drug application (NDA) or abbreviated new drug application (ANDA) require submission of additional information. All scale-up changes should be properly validated and, where needed, inspected by appropriate agency personnel.

The FDA divides scale-up into two levels.

Level 1 is defined as a: Change in batch size, up to and including a factor of 10 times the size of the pilot/biobatch, where:

The equipment used to produce the test batch(es) is of the same design and operating principles
The batch(es) is (are) manufactured in full compliance with cGMPs
The same standard operating procedures and controls, as well as the same formulation and manufacturing procedures, are used on the test batch(es) and on the full-scale production batch(es)
Level 2 discusses Changes in batch size beyond a factor of 10 times the size of the pilot/biobatch. Otherwise, requirements of level 2 are similar to level 1 requirements.

Level 1 requires:

Chemistry documentation application/compendia release requirements
Notification of change and submission of updated batch records in annual report
One batch on long-term stability reported in annual report
No dissolution or in vivo testing
Filing documentation: annual report (long-term stability commitment)
Level 2 additionally requires:

Stability testing: one batch with three months accelerated stability data and one batch on long-term stability
Dissolution documentation: case B testing
Filing documentation: prior approval supplement; annual report
Changes in process or formulation that go beyond straightforward scaling may require costly clinical and bioclinical studies to prove safety and efficacy and a prior approval statement from the FDA, which notifies you that the agency has accepted your changes. Although this may take six months or more, it may be possible to delay process validation while waiting on the results of a stability program and use the time pending FDA approval for developing validation and commercial launch or supply plans.


(Ahmed Adel Ibrahim) #4

Dear Sajjad
thanks for your reply
if i change batch size less than 10 times from production batch current produced

example (change batch size from 500 liter to 250 liter)


(HaripriyaMalireddy) #5

For change in the batch size, process validation followed by stability study is necessary, no. Of batches can be justified based on experience and scientific knowledge, because batch size change may have an impact on process parameters like equipment and capacity of equipment etc…