USP Seminar Navigating Chapter 467 Residual Solvents
13 August 2007
John Welch, scientific business manager of Principal Chemist – Chromatography attended the USP Seminar entitled Navigating Chapter 467 Residual Solvents held in Liverpool, UK.
The seminar was hosted by Dr Valentin Feyns, who is a fellow of the Monograph and Reference Standards Development at the United States Pharmacopoeia.
Following a summary of the recent history of the residual solvents monograph for which the introduction of the new procedure has been delayed several times in the last year, a detailed explanation was given of how the new procedure should be applied. Key points made were:
- Driving force - safety of the patient recommends use of less toxic solvents
- Testing is to be performed only for solvents that are likely to be present in the final manufacturing step or in previous steps and not removed by a validated procedure
- The limits for acceptable concentrations listed in the chapter are for drug products, not for its components.
- The concentration in the drug product may be calculated from contributions of components or determined experimentally if solvents are used in its manufacture and cumulative calculation exceeds limits
- Manufacturers of drug products may rely on data provided by the suppliers of components
- Provides unambiguous identification and quantification methods
- Includes options to allow use of materials that exceed the limits established
- Submission of alternative methods is not required
“The procedures described in this general chapter are to be applied wherever possible. Otherwise, manufacturers may select the most appropriate validated analytical procedure for a particular application.” (ICH and EP take similar approach) (see 1225 Validation of Compendial Procedures)
The meeting concluded with a discussion of the new procedures and their practical application. We were encouraged to make representations to the USP expert committee on the procedures which we have subsequently done, based on our long involvement with Residual Solvent Testing for various pharmaceutical companies.
