Coalition Calls for Science-Based Approach to Elemental Impurity Testing

14-May-2013 - Last updated on 15-May-2013 at 14:51 GMT

Coalition Calls for Science-Based Approach to Elemental Impurities

Differences in elemental impurity standards being developed separately by the US Pharmacopeia and ICH could mean costly reformulations according to a pharmaceutical, API and excipient industry coalition.

David Schoneker, chairman of the Coalition for the Rational Implementation of USP Elemental Impurities Requirements, told In-Pharmatechnologist.com that industry is “concerned” by a May 2014 deadline set by USP for implementing its General Chapters <232> and <233> on elemental impurities while ICH is working on its own separate technical requirements.

“Once ICH started working on this, everyone thought it might be the governing body to develop what the [elemental impurity] limits should be and the pharmacopoeia would be working on methodology,” Schoneker said. The EU and Japanese Pharmacopoeia for instance, have said they will wait on the ICH, but the USP is going ahead with their general chapters, he added.

Although the ICH has not publicly released its Q3D guideline governing elemental impurities, which is expected to come in June, Schoneker said some of the ICH and USP limits are different, such as those for arsenic. So companies could end up re-formulating a drug to meet USP standards in May 2014, and “in a year or two from now, when there’s harmony with ICH,” companies may realize they did not have to re-formulate.

USP previously told us that it would update its general chapters once ICH’s Q3D is finalized.

“Shouldn’t the USP simply say we’re putting this on hold – what’s the rush to get it out before then? There isn’t an imminent safety problem,” Schoneker added. “We want better controls on metals, and we just want better ideas that don’t create waste,” he said.

The coalition – made up of trade associations and industry groups including the International Pharmaceutical Excipients Council of the Americas (IPECAmericas), the Generic Pharmaceutical Association and the Society of Chemical Manufacturers & Affiliates – Bulk Pharmaceutical Task Force -- formally appealed to stay the USP chapters until they can be harmonized with ICH, but USP rejected the appeal.

Schoneker added that USP is still reviewing comments that the coalition made on the general chapters.

FDA Collaboration

IPEC is developing a Q&A on what still needs to be decided before industry can move forward for the FDA.

The FDA also worked with IPEC on a study in which the agency asked for samples of some excipients from naturally derived or mined materials, and companies provided the samples to a law firm that blinded them and passed them along to the agency. As there is some sensitivity by companies that “don’t know what [type of metals are in the excipients] and what can that lead to, the blinding mechanism” made it safe for the companies to supply their samples and obtain preliminary data, Schoneker said.

The FDA’s laboratory in St. Louis has since sent the results of the sample testing, which were unblinded upon their return by the law firm, back to the companies, he noted.