Report on the PQRI Impurity Characterization and Quantification Best Practices Survey

Abstract

The Product Quality Research Institute (PQRI, http:// www.pqri.org) is a consortium of industry, academia, the Food and Drug Administration (FDA), and the United States Pharmacopeia (USP) that was formed to conduct research to generate scientific information to support regulatory policy. PQRI research will identify and address potential gaps between scientific knowledge and regulatory policy to reduce regulatory burden. One of the working groups established under the PQRI’s Drug Substance Technical Committee is the Impurity Working Group (IWG). The IWG project approved by the PQRI Steering Committee was to determine if too much effort is being devoted to the evaluation of impurities during early stages of drug development. If unnecessary resources were devoted at the early stages of drug development, then the next step would be to make specific recommendations with one possible outcome being the establishment of an FDA guidance that would specifically address what is required for evaluating impurities at the early stages of drug development. Therefore, a survey was developed to determine the current practices in the industry with respect to structure elucidation, quantification, and regulatory considerations prior to agency submission. The survey was conducted in a blinded manner so that the identity of the respondents was unknown. The survey was mailed to 90 individuals who had been previously contacted to determine if they were the correct individuals in the organization to receive the survey and to encourage their participation. The original names were taken from association and trade group records. Additional surveys were distributed at the Annual American Association of Pharmaceutical Scientists (AAPS) meeting in November 2002 and the Impurity and Leachables meeting sponsored by the Institute for International Research in December 2002. Twentyfive responses were received and the analysis in this report was derived from the data of these responses. The PQRI IWG data review was finalized in June 2003. A preliminary report was presented at the PQRI workshop, BGood Regulation Through Good Science^ in August 2003. The full survey report was drafted in January 2004 and sent to the PQRI Drug Substance Technical Committee in February 2004 for review. The IWG revised draft was sent to the technical, steering, and educational committees for review from July 2004 to September 2004. The manuscript was forwarded to Pharmaceutical Research in November 2004 for review. The survey summary does not make specific regulatory recommendations but seeks to report the survey results.