cGMP and Batch Integrity of Bulk Storage Tanks

[Denis]

Seeking advice and confirmation on a discussion point, we are moving to a new facility with bulk storage tanks.

The bulk storage tank will contain 15,000 litres of alcohol - this alcohol will be pumped to a blending station. The issue concerns the batch integrity.

When the bulk tank is nearly empty we are saying that the small residual amount of alcohol that is present within the bulk tank needs to be pumped out before an additional bulk volume can be added.

To comply with GMP and ensure batch integrity we need to ensure the bulk tank is empty prior to the addition of a new alcohol batch.

Some opposition to this - production want to be able to leave say 800 litres in the bulk tank, and add a further 12,000 litres to this. This to me does not maintain batch integrity and is not cGMP compliant.

Can I have your comments please? any other alternative measures would be appreciated.

[Ederie]

With bulk suppliies of plastic, we would gather samples from the truck and test them before the driver was allowed to unload into a tank that already had material in it.
Never had any issues doing it this way (atleast not that I remember)
Ed

[Denis]

Thanks Ederie
We are proposing to test the batch prior to filling the bulk tank on delivery to the factory.

My concern is more of the dilution to the batch integrity by adding a different batch (the new one being delivered, which will be say 12,000 litres) to the current volume within the bulk tank.

The bulk tank could be contain say 800 litres of the previous batch, which would then be "contaminated" with a different batch number. Therefore we lose our batch integrity and traceability etc.

[Ederie]

Does past history show that there could be that much variation from batch to batch, or is it strictly a lot traceability issue ?

Maybe a procedure to state that as long as the remaining material is less that 10% of the new batch, or something to that effect.

Have you consulted with the supplier and / or the customer to see what they think?

Ed

[Scott Catron]

If it were me, I ask this question - what risk is there if we combine component lots in this way?

The risk is if there is a complaint, will we have lot traceability?

Let's examine the scenario:

800 liters of lot A is left in the tank. 12,000 liters of lot B is added to the tank.

The tank now contains: 6.25% of A and 93.75% of B.

Now, some time later, there is 800 liters of AB in the tank and 12,000 liters of lot C is added to the tank.

The tank now contains: 0.39% of A, 5.86% of B and 93.75% of C.

Later, there is 800 liters of ABC in the tank and 12,000 liters of lot D is added.

The tank now is: 0.02% A, 0.37% B, 5.86% C and 93.75% D.

I'll stop there, but now the question can be asked - what is the risk?

Looking at it, once this process has been implemented for a while, the tank will be 93.75% of the most current lot added, 5.86% of the previous lot, less than 0.4% of the next previous lot, and a negligible amount of all other lots.

The risk is that if there is a problem, at least two lots would have to be considered in the investigation, maybe three.

So you'd have to weigh whatever time and process savings there are with adding lots to the tank before it's empty to the possible extra time involved with investigating multiple lots of ethanol if there is a problem.

This got a little long, but I hope it helps.

[vandenbar]

If you test the new batch before you unload it and then test the comingled batch of the new 12000L and the old 800L you should be covered. We do this on an ongoing basis with petroleum base stocks. We apply the batch number of the latest batch to the comingled tank (for this example 12800 L).
You could also test the 800L before adding the 12000L to see if it still meets spec. Your only real risk here is if the product is not to spec on something you do not test for.

Clear as mud?

[Denis]

Thanks for the responses.

Let me shed some further light on the issue.

Our customers are mainly large multi national pharmaceutical companies who are demanding full batch integrity and traceability. We are working to the Orange Guide requirements and , whilst not fully GMP compliant , are working to attain this requirement.

Therefore, this requirement is being driven by customer requirements rather than an inhouse requirement.

[Scott Catron]

Originally Posted by Denis

Thanks for the responses.

Let me shed some further light on the issue.

Our customers are mainly large multi national pharmaceutical companies who are demanding full batch integrity and traceability. We are working to the Orange Guide requirements and , whilst not fully GMP compliant , are working to attain this requirement.

Therefore, this requirement is being driven by customer requirements rather than an inhouse requirement.

Then why is there even a discussion? Your customer wants full traceability, GMP requires it, so give it to them. Operations doesn't make the rules and doesn't have to face the auditors when they ask pointed questions.

Is there a compelling reason why they want to re-load the tank when there's 800 L left?