The Current Good Manufacturing Practice [21 CFR 211.194(a)] regulations require that test methods used for assessing compliance of pharmaceutical articles with established specifications must meet proper standards of accuracy and reliability. Recently, USP announced that General Chapters <232> Elemental Impurities—Limits and <2232> Elemental Contaminants in Dietary Supplements will be made applicable to all drug products and finished dietary supplement dosage forms. USP General Chapter <233> Elemental Impurities describes the procedure for the evaluation of elemental impurities, as well as the criteria for the acceptability of alternative procedures.
Elemental impurities, such as arsenic, cadmium, lead, and mercury, and others, may be naturally present in a final dosage form, added intentionally, or present as a result of variables such as environmental contaminants or reactions with primary packaging components. As such elements are characteristically detrimental to human health and in some cases drug efficacy, their presence must be determined and quantified.
As the scope of these chapters expand, new test methods are required to assess previously untested articles. Analytical methods developed for such materials need to be verified for their validity prior to use in release lot testing. In order to claim that a method is valid for such use, adequate documentation must be provided that demonstrates the successful completion of method validation for each element of interest, therefore demonstrating procedure is suitable for its intended application(s).
Although General Chapters <232> and <233> do not officially replace USP <231> Heavy Metals until January 1, 2018, USP has encouraged preemptive implementation of these more stringent chapters to further product quality and safety, but also allow for sufficient time for companies to develop and implement required methods. Following this recommendation, Whitehouse Labs acquired an Agilent Technologies 7900 Series ICP-MS in December 2014. As more companies move to the adoption of the new and revised chapters, the ICP-MS has been increasingly used for validation of methods and analysis of elemental impurities in drug products, excipients, dietary supplements, etc.
The Quality Assurance Unit at Whitehouse Laboratories provides assurance that validation of methods intended for use in assessing elemental impurities is carried out in accordance with <1225> Validation of Compendial Procedures. Through our internal Method Validations, Whitehouse Laboratories demonstrates that the requirements set forth during Method Validation meet and are equivalent for use to Compendial procedures. The Quality Assurance Unit is responsible for verifying that all Method Validations performed internally include checks for accuracy, precision, specificity, detection limit, quantitation limit, linearity, range, and robustness, and that these checks meet all defined criteria. Once validation is complete, it is reviewed by laboratory management, and final approval is made by the Quality Assurance Unit, at which point the method is considered validated, and testing for release lot testing can be executed. Validated methods for routine analysis can be then be transferred back to the client site, maintained at Whitehouse Labs for the routine analysis of the specific material. With the increase in demand, and pending requirements for such testing, Whitehouse Labs aims to extend its distinguished level of quality and expertise to this growing area of service.