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How to diagnose a production batch failure
Nothing works perfectly every time…
So, you made a successful lab batch, you made a successful pilot batch, now it’s time to make a production sized batch. And…it failed. Doesn’t match the lab/pilot batches badly enough that you can’t sell it. What do you do?In a perfect world, you would already know what to do - you would have already made lab batches with big +/- variations in each of your ingredients, so that you knew what your product looked like if there was a weighing error. You would have already done a series of knock-out experiments, so you’d know what your product looked like if the production compounders left an ingredient out. You would have already made lab batches with the same lots of ingredients that were going to be used for the production batch, so that you could be certain that there was no variation in the quality of the ingredients between what you used in the lab and what would be used in production.Unfortunately, we don’t live in a perfect world - at least not anymore. When I started in the cosmetic industry, all of the above steps were taught to me as being standard practice (at least for an important product). But at the time, companies could afford to fully staff their R&D departments. Now, every company I’ve ever heard of, from the largest to the smallest, is running R&D so lean that they are barely above the absolute minimum of people required, if that - which means that none of us have the time to do all the prep work I listed above.So, back to our failed batch. The very first thing you have to do is check the production records to see if you can spot any discrepancies. The next thing you must do is to pull samples of the same lots of ingredients that were used for the production batch, and compare them to the ingredients you have in the lab. Once you’ve determined that they are the same ingredients with the same specs (as much as you can, anyway), make a lab batch with the same lots of ingredients that were be used for the production batch.Now, we evaluate. The lab batch will tell us a lot. First, did the batch behave during processing the same way as the batches you made initially in the lab? Second, did this lab batch match your initial lab batches, or did it match the failed production batch? (If it doesn’t match either, you have bigger problems than I can help with).Conclusions/diagnosis -1) If the lab batch behaved during processing the same way as the batches you made initially in the lab, and the finished product matches your initial lab batches, congratulations! You have successfully ruled out most formulation problems, and any raw material problems. There is, however, an issue with processing. Something is wrong with the way production has processed the batch. You must evaluate your production process and compare it to your lab process, but how to fix that is too long to address here.2) If the lab batch did NOT behave during processing the same way as the batches you made initially in the lab, but the finished product matches your initial lab batches, then you have successfully ruled out most formulation problems, but identified a raw material problem and an issue with production processing. Something is different/wrong with the way production has processed the batch, and at least one of your ingredients is bad. Now you have to run a series of knock-out experiments to identify the culprit(s), and then evaluate your production process.3) If the lab batch either did or did not behave during processing the same way as the batches you made initially in the lab, and the finished product matches your production batches, then you have successfully ruled out almost all formulation problems, and clearly identified a raw material problem. At least one of your ingredients is bad. Now you have to run a series of knock-out experiments to identify the culprit(s), and then get new lots of the bad materials and re-run your production batch.Can anyone think of a step I’ve left out? -
3 Replies
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This is excellent, thank you @bobzchemist.
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This is great as a general starting framework for identifying scale up issues. I’ve found some of the following practices to be also very helpful:
-Run a % solids test - If you have a moisture balance analyzer, running a quick % solids test on a lab batch and comparing it to the production batch can give you some useful information.-Run analytical tests - For products with actives that can be assayed, you can run various analytical tests (GC, HPLC, etc.) to determine the level of actives in your lab batch or possibly identify impurities in the production batch.-Specific Gravity comparisons - If the SG of the production batch is way off, you can take a look at the SGs of the raw materials and possibly identify which materials are part of the issue. -
Even simpler, test your pH first, especially with shampoos when thickening is an issue. I get about 5 “emergency” calls a year…”My shampoo isn’t thickening.” I ask “What is the pH?” Half an hour later I usually hear “Never mind, it’s fixed.”
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