The International Conference on Harmonisation (ICH) made the clarification in the latest version of a Q&A document this week, explaining that manufacturers either need to meet all of the general principles in section 5 of Q11 or explain why not.
“Applicants should consider all of the ICH Q11 general principles in the selection and justification of proposed starting materials, together with the clarifications in this Q&A document, rather than choosing just a few of the general principles and using them to justify starting material selection.
“If a proposed starting material does not meet all of the general principles, a rationale should be provided explaining why the starting material is considered appropriate.”
Q11 explains how principles detailed in Q8, 9 and 10 apply to active pharmaceutical ingredient (API) production and makes clear the information drug companies must include in common technical documents (CTDs).
It was adopted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in 2012.
But despite being in place for five years, industry still needs clarification on how best to meet the standards set out in Q11 according to the ICH.
Custom made starting materials
The Q&A document – a draft version of which was published last November - also defines what constitutes a “custom synthesised chemical” and explains how they differ from "commercially available" compounds under Q11 and how their use should be justified.
According to the ICH “an applicant generally need not justify the use of a commercially available chemical as a starting material, whereas a custom synthesised chemical proposed as a starting material should be justified in accordance with the ICH Q11 general principles.”
The document goes on to explain that just because a chemical is available commercially manufacturers should not assume it will be defined as “commercially available” under the guidelines.
“The availability of a chemical from multiple suppliers should not be the sole basis for the designation of a chemical as a commercially available starting material. This includes situations where a custom synthesized chemical has become available over time from multiple suppliers.”
“Such chemicals should still be justified according to the ICH Q11 general principles for selection of starting materials” the ICH says.
Conversely, chemicals made in small quantities can be defined as “commercially available” under Q11 “provided that the scale is sufficient for the manufacture of the drug substance and that the chemical is also used in a pre-existing, non-pharmaceutical market.”