Selecting the worst case

Hi to everyone,

I’m a Pharmacist working in an QA department. I can’t tell you how happy I am, because I’ve found this site. But I’ll have a question. I would be very glad, if someone could help me.

We produce over 40 medicines and 2 of them are veterinary drugs. Those veterinary drugs are "oblet"s, so they weigh about 13.000mg’s. When selecting the worst case, we chose the most insoluble and toxic product, which has alos the lowest LTD value within our products. So far no problems.

But when we use the MC= LTD/1000/D x Wb/Wt x Ss/Se x R formulation, we should choose the biggest Wt value, which is the biggest, heaviest tablet. Our biggest tablet weigh 1841 mg’s. But our veterinary product weighs 13.000mg’s. If we use the veterinary in our formulation the Mc limit comes 5 times lower. But I think, no human will use those veterinary products. So could we use the most biggest tablet weight for human in our formulation, our should we use our veterinary products weight?

I hope I didn’t bother you too much.

Thank you.

r u manufacturing veternary products in same facillity in which u r making human products…


Yes we are. I don’t think that it’s a problem.

You should definitetly validate your cleaning procedure to avoid cross contamination. I think you should use your veterinary product as the worst case, due to the potencial harm it could make if your next product is a human product, that´s enough to justify that.

When defining your worst case, take into account that you must actually define two “worst cases”: One is the worst target substance, which is usually the API hardest to clean, most potent, most insoluble, etc., etc. The other is the potentially contaminated product, which is necessary to calculate the acceptable limit of contamination, and is the worst combination of highest tablet weight, maximum daily intakes and lowest batch size (for the same level of contamination in the equipment, it is worse a “contaminated” product with batch size 400 kg, 600 mg tablet weight and three daily dosages than a product with batch size 500 kg, 500 mg tablet weight and two daily dosages). So, if you want to be on the safe side, your approach is OK in taking the veterinary dosage as “contaminated” product, but to get reasonable contamination levels choose the worst "contaminated " product from the human product line and the worst contaminant from all the target substances processed in the equipment.

I have chosen visual cleanliness parameter for selecting the worst case. What I have done is that first of all I determine the level of visual cleanliness concentration & found that as 4.05 microgram per square cm at my company at particular lux (not mentioned). Then I also calculate the surface area of my equipments and then calculate the limit on the basis of 10 ppm and dose criteria. Then I compare all the limits.

In those products where I found visible criteria as the most stringent criteria, I remove those products from the list of the worst case as they can be check every time after cleaning process and I do not think need of validation for those products. And that reduces my vaidation load to high extent. After then only I chose the solubility criteria. I do not need to calculate the MAR again as I have already calculate that during comparison to visual method.

Hope this will be very helpful for you.

Prawan Dahal