The US Pharmacopeial Convention (USP) has introduced new elemental impurity standards to replace what it says were outdated guidelines.
The organisation said its two new testing criteria – named ‘Elemental Impurities-Limits’ and ‘Elemental Impurities-Procedures’ – mean drugmakers can detect previously unheard-of contamination issues thrown-up by modern analytical methods and processing equipment.
“The test methodology—while widely used—is based on a longstanding technique not sufficiently sensitive to detect a number of impurities at levels known to be toxic,” USP said in a statement.
“It applied only to active pharmaceutical ingredients and excipient,” the convention added, saying the new advisories will apply to an industry-wide range of materials and substances.
A rise in development of high toxicity compounds was high on the list of problematic new developments for the old testing standards.
Anthony DeStefano, USP’s senior VP of compendial sciences, told in-PharmaTechnologist: “The previous standard for the detection of elemental impurities applied a longstanding technique that was not sufficiently sensitive to detect a number of impurities at levels that are now known to be toxic.”
He said the old testing guidelines were also extremely ambiguous so that it was often impossible to not distinguish one element from another, and were “difficult to perform properly.”
The standards also tended to involve toxic reagents, DeStefano told us, hence defeating the object of testing for impurities.
“The new standards provide procedures for the detection of selected impurities in drug products based on modern analytical methods, as well as acceptable limits for their presence based on toxicity data and exposure levels,” he said.
The uptick for manufacturers
The new guidelines will become official this December.
However a loophole – the standards will not be applicable to all articles in the compendia until a new provision in USP-NF's General Notices comes into play – means the guidelines are not compulsory to be compliant with USP conventions until May 1, 2014.
“Thus, manufacturers will have time to transition before the standards come into effect,” DeStefano told us.
He added: “The development of these new standards has been taking place for some time, so the change is not going to come as a surprise to industry.”
However, despite the generous time frame and forewarning of the changes, USP is still aware the move means more workload for manufacturers.
“This will involve extra work,” said DeStefano. “At least initially, as drug product manufacturers along with drug substance and excipient manufacturers develop procedures to better understand the levels of elemental impurities in their products.
“In addition, manufacturers of finished drug products will have to work closely with their suppliers to assess the quality of their materials.”
DeStefano urged industry players to act now. “We have heard from several members of industry that they have already started to prepare for this coming change by incorporating the necessary instrumentation and expertise within their organisations,” he said.