EP and USP Heavy Metals Testing Harmonisation. On the surface it appears that the EP is following the USP in moving from the current harmonised colorimetric limit test for heavy metals to a quantitative instrument based method. Unfortunately having studied both pharmacopoeia proposals, it would appear that the idea of keeping a harmonised method has been lost.
Several years ago the USP announced its intention to move away from the Colorimetric Heavy Metals Limit Test to a quantitative instrument based approach. This has been published in the form of two monographs: Elemental Impurities – Limits and Elemental Impurities – Procedures . Essentially the USP are recommending the test be performed using ICP following Microwave Digestion. These methods are to become effective in 2013.
At the time the EP said they would not be following the same route, but in the April 2011 edition of the Pharmeuropa Vol 23 No. 2 they have proposed two new monographs: Metal Catalysts or Metal Reagents 2.4.20 and Metal Residues 5.20, which follow the same basic principles as the USP.
On first reading both proposals would appear to be very similar in their approach. However, on closer inspection, the list of metals to be determined is different:
The EP states: The European Pharmacopoeia (Ph. Eur.) applies this guideline to all pharmaceutical substances and medicinal products whether or not they are subject of a monograph. All substances and products are to be tested for the content of metals likely to be present in a substance or product. This guideline applies to new and existing marketed drug products. However, for existing marketed drug products a time limit of 5 years is set for the implementation of the guideline in case an earlier implementation is not feasible. Following this 5 years implementation, transitional period only drug products which have been manufactured using pharmaceutical substances which comply with the guideline can be released to the market.
This means that the time frames for implementation will be different.
It is our opinion that whilst the move to the quantitative instrument based method is long overdue, it is a retrograde step to lose a harmonized method. As a contract analytical testing facility we may have to return to undertaking two different procedures for clients to confirm the absence of heavy metals from a single sample, during the implementation period.
Both pharmacopoeias have asked for feedback on these proposals and from our understanding are getting only a limited response. We would encourage our clients to make themselves aware of these new requirements before they are implemented and make their views known to the relevant organizations.
For more information on this please don't hesitate to get in touch.