Monographs, heavy metals and globalisation on USP agenda

This year the US Pharmacopeia (USP) held a pre-AAPS workshop on impurities, adulteration and its changing role in global drug quality. At the workshop changes to elemental impurities guidelines, including the move away from the precipitation test, were among the topics discussed.

Anthony DeStefano, vice president, general chapters at USP, told in-PharmaTechnologist the visual lead sulphide precipitation test is limited by reliance on the human eye. Shortcomings were first raised in the Pharmacopeia Forum in 1995 and the USP is now working to improve testing.

Initial work identified four critical contaminants, lead, arsenic, mercury and cadmium, and 12 catalysts, taken from European guidance, which should be monitored. The International Conference on Harmonisation (ICH) is now involved and other metals are being considered.

Limits for the critical contaminants, known as the ‘big 4’, are also being discussed. DeStefano said the goal is to have a provisional list of elements by June 2011 with a stage two draft to be published sometime later.

Industry input, other dosages​

Throughout this process the USP published updates in the Pharmacopeial Forum​ and sought input from industry at various meetings. Now the ICH is involved the industry accepts changes will happen, said DeStefano, but the implementation date is still under discussion.

As it stands the USP is focusing on impurities in oral dosage forms. Once this is complete the USP may consider revising guidelines for intravenous drugs but will probably, for now at least, stay away from other dosage forms, such as inhaled or ophthalmic treatments, said DeStefano.

These make up a small proportion of all drugs and there is little relevant toxicology data. Some data is available from smelting but it is unclear how this can transferred and made relevant to the pharmaceutical sector.

Renewed interest, global presence​

Roger Williams, CEO of the USP, told in-PharmaTechnologist “there is renewed interest in the pharmacopeia, good manufacturing practices (GMP) and the supply chain​”. This is, in part, a result of high-profile contaminations and the USP is working to stop these occurring again.

Collaborating with the US Food and Drug Administration (FDA) to update monographs is part of this effort. The USP is also increasingly working with other national regulators to support drug quality around the world.

For example, Ukraine and Kazakhstan are adopting and adapting text from the USP and a similar agreement with Indonesia is being worked, said Williams. Forging these links, while maintaining a strong relationship with the FDA, is intended to help the USP better serve all regions.

Spectral libraries​

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Williams said spectral libraries are “an exciting area​” and this topic was discussed in greater detail at the workshop by Ed Zhao from the USP. Zhao said near-infrared spectroscopy (NIR) and Raman can be used to gather information to support anti-counterfeiting efforts.

A USP project, which is still at a very early stage, proposes collating this information in a spectral library to help regulators, manufacturers, wholesales, pharmacies, customs and law enforcement.