20/21 April 2021
According to the Guideline ICH Q11 "Development and Manufacture of Drug Substances (chemical entities and biotechnological/biological entities", the chemical substance must be defined in the early drug product development phase which is used as the starting material for the manufacture of the API. This "Starting Material" marks the point in the route of synthesis where GMP conditions have to be applied. According to ICH Q11, the criterion for the definition of a starting material is its molecular structure and it should already contain a significant structural element of the subsequent API. Yet, the further statements in Chapter 5 of the ICH Q11 Guideline on starting materials aren't so straightforward and have led to misunderstandings and misinterpretations in the months following the publication of the guideline. Disagreements between applicants and the assessors of the regulatory authorities processing the applications are rather almost the rule.
This situation drove the EMA to release a document entitled "Reflection paper in the requirements for selection and justification of starting materials for the manufature of chemical active substances". The paper was published on 10 October 2014 on the website of the Agency and aims to clarify the selection of starting materials for synthetic and semi-synthetic APIs as well as the justification of such a selection. Within in total 11 so-called "explanatory notes" the Agency presents its expectations from the applicants regarding the information about an API starting material in a marketing authorisation application. Find below some examples:
The future will show to what extent EMA's document contributes to the clarification of misunderstandings between applicants and regulatory authorities.
Note: At the 17th APIC Conference on 5 - 7 November 2014 in Vienna, Austria, you will get first-hand information on the topic from an EMA representative.