FDA Answers Key Residual-Solvent Testing Questions

The US Food and Drug Administration has answered some core industry questions regarding the changes made to US Pharmacopeia General Chapter <467> in July 2008 with an unofficial guideline. The agency issued a draft guidance in August 2008 to help industry implement the chapter’s new standards, but several concerns and questions remained. (See back story and blog post.)

To gain clarification, industry representatives from the International Pharmaceutical Excipients Council, the Generic Pharmaceutical Association, the Consumer Health Products Association, and the Pharmaceutical Research and Manufacturers of America, among others, established the Coalition for Rational Implementation of USP <467> and have been carrying out a dialogue with FDA’s Office of Generic Drugs and Office of Pharmaceutical Science since last fall.

As a result of the Coalition’s work, FDA agreed in November 2008 to work with industry to put together an industry guidance document to address core questions related to the chapter and its new requirements. That document, although not an official regulatory guidance, has been reviewed by FDA, according to David R. Schoneker, coordinator of the Coalition and former chair of IPEC-Americas. FDA is in agreement that the answers to the core questions that they had provided to the Coalition during a Nov. 7 teleconference are properly described in this document. FDA is also supportive of the Coalition providing this document broadly throughout industry and the media to get the word out on the agency’s current thinking regarding this topic, according to Schoneker.

“The goal is to help companies better understand FDA's expectations when filing residual solvent information with abbreviated new drug and new drug applications,” Schoneker says.

Some questions addressed in the document include: Why are active pharmaceutical ingredients not listed in the language? What type of evidence does OGD expect to see in submissions to verify that the sponsor understands the manufacturing process and controls regarding 467 levels? And, What is required for a Class 2 or Class 3 solvent to be considered “likely to be present” in the product?