The ICH Q11 Guideline on Development and Manufacture of Drug Substances ( Chemical Entities and Biotechnological/Biological Entities). Step 3. Transmission to CHMP. May Adoption by CHMP for release for ICH guideline Q11 on development and manufacture of drug substances . endorsed by the ICH Assembly at Step 4 of the ICH process, August Do the ICH Q11 general principles for selection of starting materials apply to the.
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These concepts should logically be applied to steps upstream of the starting material as well. The distinction between these two terms plays an important role in ICH Q11 insofar as that an applicant does not have to justify the use of a “commercially available” substance as a starting material in the dossier – on the contrary to “custom synthesised” sfep those are subject to the regulations of ICH Q According to ICH Q11, a “commercially available substance” is one that is offered and sold as a commodity in the non-pharmaceutical market in addition to its use as a starting material.
The selection of a starting material for the synthesis of an active substance and its justification is often one of the most crucial steps in the approval process.
In that case, the dossier has to describe a control strategy and justify the choice of starting material. If a persisting impurity appears at some point during a synthetic route, it may be acceptable to control this impurity through the specification of the starting material, even if the impurity profile of the active substance is changed.
Yes, the terms are synonymous. When related substances are at a level that exceeds those limits, an impact on the impurity profile is to be expected. Assessors at regulatory agencies of the EU member states have to evaluate whether the data provided sufficiently justify the selection.
The ICH Q11 Q&A reaches Step 4 of the ICH Process : ICH
The criteria for this are outlined in the ICH Q11 guideline – however, not in a sufficiently precise manner. This resulted in questions and additional demands by the agencies, thereby delaying the approval processes.
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It remains to be seen whether this will speed up approval processes. The same goes for intermediates that do not count as “commercially available” according to ICH Q This means impurities which are not purged over multiple synthesis steps and possibly remain in the final product e.
The term “custom synthesised” is not defined in ICH Q11; it is generally understood to be a substance which has been synthesised specifically for pharmaceutical manufacture and in consideration of a customers’ requirements. However, the regulations in ICH Q7 relate to the GMP compliant manufacture of active substances, not the procedure of selecting and justifying starting materials.
ICH Q11 reaches Step 4 of the ICH Process
Changes in wtep synthesis steps upstream must be made in accordance with the quality assurance system of the applicant. In total, the document contains 16 questions and their corresponding answers, all of which refer specifically to the guideline ICH Q11, chapter 5 ” Selection of Starting Materials and Source Materials “.
Together with the recently published updated EMA reflection paper on API starting materialsthe applicants as well as the assessors are now provided with sufficiently detailed documents, which lay the foundations for a more harmonised interpretation of ICH Q ICH Q11, section 9 describes basic scientific and risk-based concepts for the evaluation of post-approval changes to the starting material.