100 year-old rules on API impurities to change in 2015

By Fiona BARRY

- Last updated on GMT

(Picture credit: Jean-Pierre/Flickr)
(Picture credit: Jean-Pierre/Flickr)

Related tags Elemental impurities United states pharmacopeia

API manufacturers are gearing up for changes to regulations on elemental impurities made by the US Pharmaceopeia (USP).

German API (active pharmaceutical ingredient) supplier ChemCon told us it has expanded its Quality Control department ahead of changes to the way producers must test for elemental impurities and inorganic contaminants in pharmaceutical ingredients.

Two chapters in the USP-NF​ (United States Pharmacopeia and The National Formulary), the written guide of the United States Pharmacopeial Convention (USP) will be introduced next year, laying out new tests for impurities to replace the 100 year-old  “Heavy Metals Test” currently in use.

The original date for implementation of the changes – devised in February 2013 – was this month, but the launch has been pushed back to January 2015, USP’s spokeswoman told us.

The ‘Big Four’

The old rules, which date back to the 19th​ century, are not only not specific, but not objective,​” Tobias Timtner, spokesman, Colorcon, told in-Pharmatechnologist.com.

The current tests can be difficult to conduct and can fail to detect some important elements at toxicologically-relevant levels, such as mercury. The focus of the latest rules is on patient safety, he said.

The number of specific substances to be tested for will now vary, according to a risk assessment of the ingredient and the process. However in every case API makers will have to “communicate a list of all catalytic metals that were used in their synthesis and, where possible, the content of those residual metals and the ‘Big Four’ (cadmium, lead, arsenic and mercury) for each batch,​” said Theresa Laranang-Mutlu, US Pharmacopeia spokeswoman, told in-Pharmatechnologist.com.

Mass spectrometry

USP will also make compulsory the use of inductively coupled plasma mass spectrometry (ICP-MS) to perform these tests.

ChemCon has invested in a new ICP-MS system in preparation for the changes, as well as a microwave sample digester. The company chose Thermo Scientific’s ICAP Q mass spectrometry equipment, Timtner told us, for its consistent results. He added the company also offered NMR (nucleomagnetic resonance) analysis to try to get an edge on its custom manufacturing competitors.

Timtner said companies are starting to ask ChemCon to produce APIs conforming to the stricter rules which will come into effect next year. “We were talking to a customer which gets some of its supply from another company. They’re looking for a new supplier because this API already has very high concentrations [of impurities] in it and currently it would fail the regulations.” ​One of the common reasons leading to heavy metal contamination in API production is having a metal catalyst, he said.

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