USP delay is no surprise

The USP has announced a delay in the implementation of General Chapter <467> Residual Solvents, which concerns new medicines coming to market and existing pharmaceutical articles in USP-NF. Originally due to come into force on Jan 1^st 2007, implementation was then delayed until July 1^st 2007 and is now set for July 1^st 2008.

Since residual solvents are one of the main categories of impurities that can occur within pharmaceutical articles, it is essential to have reliable methods for checking that these impurities are controlled and comply with recommended limits. 

The delay to the implementation recognises the time and resource impact on manufacturers in applying the requirement to drug substances, excipients and drug products in the USP-NF.  Moreover, difficulties in applying the prescribed USP methods to water soluble articles have been reported where sensitivity has been poor. These difficulties are compounded when analysing water insoluble articles where the combination of low sensitivity and peaks arising from minor impurities in the chosen solvent (DMF/DMA) obscure chromatographic detail. 

"As general methodology moves the industry to a common standard, its application as being all encompassing is not always possible and can prove problematic for certain pharmaceutical articles," says Elma Brennan of contract laboratory RSSL Pharma. "Often it is more effective to develop and validate screening methods that target solvents used for a particular product and process. RSSL Pharma has over 10 years experience in developing and validating residual solvent methods. For problematic analyses, our recommendation would be to focus on specific solvents used in the manufacturing process rather than waste energy and expense applying methods which screen to cover every situation.

"While the delay in implementation of the General Chapter <467> provides a welcome reprieve to deal with problematic analyses, the sheer number of articles that will require testing will put significant pressure on pharmaceutical manufacturers as they seek conformance with this standard."