I Want To Know The General Procedure Used To Fix The Residue Limit In Case Of A Dose Forming Step, Eg, For Compression Machine Or For Capsule Filling Machine.
hello??? My query still remians unanswered. Anyone out there who can help on this?
Dear Lalit,
this is only in order not to leave your post unanswered. The issue of the operations you mention (not only dose forming steps but every process step after the last step with mixing action (tabletting of uncoated tablets, tablet imprinting, blister packaging, etc.) is well known but there is no universally accepted way to approach it, without extremely complicated tests or somewhat strange assumptions. One approach is to consider that the whole contamination present in the equipment is carried away with the first hopper filling, assuming (and here the strangeness comes in) that the contamination is uniformly distributed in this first hopper load. Another approach is analizing the first tablets to come out for traces of contamination, without any assurance that the granulate with which these tablets were compressed actually has had contact with the machine, or if it stems from the middle of the hopper without surface contact. The third approach is to set an arbitrary limit with an additional safety factor. We have approached it in such a complicated way that we won’t repeat it ever, which was the determination of traces of contamination in placebo tablets compressed from the first hopper load, in order to get a “decay curve” of contamination as compression goes on. The results were not too promising, because obviously the contamination is not being taken away in a steady way but rather shows “peaks” as the portions of granulate in contact with the machine surfaces go into the dies, and on top the conciliation of the contamination spiked in the hopper and filler was not possible (spiked contamination should equal the sum of contamination encountered in the tablets), indicating that the contamination had not been removed with the first hopper load. All this with an extremely high analytical load, method revalidation, and so on.
Probably this is not too helpful, but at least you know that you are not alone out there!
Best regards
Alfred
Dear Lalit,
this is only in order not to leave your post unanswered. The issue of the operations you mention (not only dose forming steps but every process step after the last step with mixing action (tabletting of uncoated tablets, tablet imprinting, blister packaging, etc.) is well known but there is no universally accepted way to approach it, without extremely complicated tests or somewhat strange assumptions. One approach is to consider that the whole contamination present in the equipment is carried away with the first hopper filling, assuming (and here the strangeness comes in) that the contamination is uniformly distributed in this first hopper load. Another approach is analizing the first tablets to come out, for traces of contamination, without any assurance that the granulate which these tablets were compressed with actually has had contact with the machine, or if it stems from the middle of the hopper without surface contact. The third approach is to set an arbitrary limit with an additional safety factor. We have approached it in such a complicated way that we won’t repeat it ever, which was the determination of traces of contamination in placebo tablets compressed from the first hopper load, in order to get a “decay curve” of contamination as compression goes on. The results were not too promising, because obviously the contamination is not being taken away in a steady way but rather shows “peaks” as the portions of granulate in contact with the machine surfaces go into the dies, and on top the conciliation of the contamination spiked in the hopper and filler was not possible (spiked contamination should equal the sum of contamination encountered in the tablets), indicating that the contamination had not been removed with the first hopper load. All this with an extremely high analytical load, method revalidation, and so on.
Probably this is not too helpful, but at least you know that you are not alone out there!
Best regards
Alfred