Posted 07 September 2017
By Michael Mezher
The International Council for Harmonisation (ICH) on Wednesday advanced a questions and answers guideline aimed at clarifying expectations for selecting and justifying starting materials for drug and biologic manufacturing.
The document, which the ICH assembly adopted in August and first released for consultation in December 2016, is meant to expand on ICH's 2012 guideline on drug substance manufacturing, Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities).
"Since the ICH Q11 guideline was finalized, worldwide experience with implementation of the recommendations on the development and manufacture of drug substances has given rise to requests for clarification relating to the selection and justification of starting materials," ICH writes.
ICH also says the Q&A document will help sponsors determine what information about their starting materials they should provide in regulatory submissions and master files.
According to ICH, applicants should consider all the general principles laid out in ICH Q11, as well as the clarifications in the Q&A document, when looking to justify their starting material selection rather than picking and choosing certain principles from the guidelines to follow.
ICH also says that starting materials in already-approved products will generally not need to be re-justified based on the principles in ICH Q11 or the Q&A document, "unless significant changes are made to the manufacturing processes and controls."
But ICH adds that just because starting materials have been accepted for one manufacturer's processes does not mean they will be appropriate for another manufacturer if a proposal does not comply with the Q11 principles.
In total, the document provides answers on 16 questions related to ICH Q11, including questions on when ICH Q11 principles apply, differences between commercially available and custom synthesized chemicals and considerations for dealing with impurities.
The Q&A also includes a two-part decision tree meant to walk manufacturers through the general principles of ICH Q11 to help them determine whether they should redefine their starting material or if it is suitable to be proposed as a starting material in an application.