« Quality Assurance & Control

It is ineresting,

Need to know whether we need to cover such tests during stability study as they are normally coming from process and are not bound to increase during storage. 

Good, I am yet to see this. If it covers finished dosage form, it will be excellent. At least some uniformity we can bring in to address the extractables studies with respect to the  in-organic impurities.

Hi viswanatha!

The same was expeted long ago. A study was conducted based on the general experience on the variability and non-reliablility of wet chemical tests for upto 69 heavy metals. It was stated that  "Although still widely accepted and used in the pharmaceutical industry, these methods based on the intensity of the color of sulfide precipitation are non specific, insensitive, time consuming, labor intensive, and more often than hoped, yield low recoveries or no recoveries at all." (Wang, T. et al, J. Pharm . & Biomed . Anal., Vol. 23 (2000) 867 890) Pharm. Biomed. 867-890).

It was concluded from this study that approximately 50% of the metals may be lost during the ash process. Metals like mercury, which is one of the more toxic heavy metals, was not recovered at all. Thus because of the loss of metals during ignition, the validity of test results obtained with the current USP, JP and EP general test procedures is questionable.

Some companies have already started using techniques like ICP-MS and ICP-AES for that purpose. The future of pharmacopoeial seems to be moving from qualitaive and semiquantitave techniques to more reliable and advanced qauntitative techniques wherever possible.

Thanks

Tarun

Tarun, thank you for providing some good insight into the possible background to the new proposed General Chapter.

As you can understand while there'll be ideas, papers & debates, changing a pharmacopeial method isn't easy, as consensus from the stakeholders (Industry) is a very important component of any revision. A very classic case is the General Chapter <467> for Residual Solvents that has become official only in July 2008 despite years spent by USP proposing & pursuing the same.

You may find it interesting that despite the obvious superiority of the proposed new techniques (ICP-MS, ICP-AES), a majority of the Industry is still reluctant to show its full support to the new general chapter as the methods are supposedly 1) not too easily accessible to all sizes of Pharma & 2) a tad to specific to digest (the regulator would be strengthened to question your results more - rigth?!) - I personally met many in Industry who felt these changes should not be rushed through and USP should look at possible alternative techniques to ICP-MS, ICP-AES that are definitely semi-quantitative/ quantitative but not cost intensive.

moreover, pharmacopeial standards are minimal standards that are driven by 'better access of safe medicine' rather than the desire to impose the 'latest & the most stringent science' on the manufacturing industry despite the cost and other access related implications... the response to USP on the proposed revisions need to be tempered by this backgrounder too.. 

It would not seem likely as they cannot increase or decrease with time.

Dear Narayanappa,

As you mentioned, the inorganic impurities are forming during the course of the reaction which will not be getting increased during the stability study.

So I think it is not required to perform the test during the stability study since it has no valid scientific reason to perform the test.

One more information I just wanted to share with the forum is, Its very nice to hear that we are moving towards the quantitative determination of Inorganic Impurities using the sophisticated instruments like ICP MS. We have to insist on the implementation of the same in USP.

The small and medium size companies which can't afford to buy the instrument will be making use of the commercial labs for testing their samples.

Regards,

Navaneeth.