How many batches have to be kept under Stability Studies

raghu_1968 · Apr 12, 2012

The query is related to API (Active Pharmaceutical ingredient)

There is a change with respect to input batch size. Proportionately the other raw materials will also get increased.

Except the scale change there is no change in the process.

Hence, it is decided to go for validation.

The query is how many batches have to be kept under stability studies (from the scale up)?

All the validation bathes needs to be kept under stability for both conditions or one batch from the validation batch under long term condition is enough?

Is there any guideline reference for this?

Regards / Raghu

Ronen E · Apr 12, 2012

raghu_1968 said:
The query is related to API (Active Pharmaceutical ingredient)

There is a change with respect to input batch size. Proportionately the other raw materials will also get increased.

Except the scale change there is no change in the process.

Hence, it is decided to go for validation.

The query is how many batches have to be kept under stability studies (from the scale up)?

All the validation bathes needs to be kept under stability for both conditions or one batch from the validation batch under long term condition is enough?

Is there any guideline reference for this?

Regards / Raghu

Does this help?

http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html

BTW, if the scale change is anything but very minor, don't automatically assume that keeping all ingredients in proportions will suffice. You may be up for some surprises concerning uniformity / consistency, heat effects etc. If the costs of making a full scale batch is high, you might want to reconsider going straight to validation, because you may have to dump some...

Ajit Basrur · Apr 12, 2012

raghu_1968 said:
The query is related to API (Active Pharmaceutical ingredient)

There is a change with respect to input batch size. Proportionately the other raw materials will also get increased.

Except the scale change there is no change in the process.

Hence, it is decided to go for validation.

The query is how many batches have to be kept under stability studies (from the scale up)?

All the validation bathes needs to be kept under stability for both conditions or one batch from the validation batch under long term condition is enough?

Is there any guideline reference for this?

Regards / Raghu

In case of scale-up, there is definitely a great impact on lending operations and thus I would still go with 3 initial batches for Stability.

Regarding guidelines, Q7A would be still a great reference. Refer HERE

raghu_1968 · Apr 16, 2012

Q7A states as below:

“Normally the first three commercial production batches should be placed on the stability monitoring program to confirm the retest or expiry date. However, where data from previous studies show that the API is expected to remain stable for at least two years, fewer than three batches can be used.”

As mentioned earlier, except scale-up there are no other changes. Is it acceptable to have a single batch on stability from the scale up batch?

Ajit Basrur · Apr 16, 2012

raghu_1968 said:
Q7A states as below:

“Normally the first three commercial production batches should be placed on the stability monitoring program to confirm the retest or expiry date. However, where data from previous studies show that the API is expected to remain stable for at least two years, fewer than three batches can be used.”

As mentioned earlier, except scale-up there are no other changes. Is it acceptable to have a single batch on stability from the scale up batch?

You could but have to provide a solid rationale. Three is an acceptable number to FDA and other regulators and hence I prefer 3 batches.

Its your call

Ronen E · Apr 16, 2012

raghu_1968 said:
...However, where data from previous studies show that the API is expected to remain stable for at least two years...

Q: Do you have such data?

My A: No, because apparently previous studies were done on the smaller scale batches. I don't know your processes, but from my limited experience significant scale-up must not be automatically assumed to behave "linearly".

v9991 · Apr 28, 2012

I agree with Ronen & Ajit...
what i would like to add is , the emphasis&need on risk assessment; (solid rationale...)
usually the manufacturing process includes atleast couple of steps; if the batch size is increased for 1-step...and process rest of steps unchanged (lot wise processing).
even then we have to establish the effect of hold time of each lots...etc.,and its impact on rest of the product...

hope that helps.

How many batches have to be kept under Stability Studies

raghu_1968

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Ronen E

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Ajit Basrur

raghu_1968

Involved In Discussions

Ajit Basrur

Ronen E

Problem Solver

v9991

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