November 2022
Real CMC Tips and Insights

published 15 Dec 2022

Since the beginning of July 2020, we have published weekly Regulatory tips and insights from our Regulatory experts on our Real Regulatory LinkedIn page, as a service to our followers. The tips we published in November 2022 are collected here, for convenience. Make sure you follow  Real Regulatory Ltd and Real CMC for regulatory news, reports and hints.


Updating a QOS

It is good practice to keep your Quality Overall Summary fully updated at all times, even if not strictly required by competent authorities. When done properly, the QOS focuses on the salient points of Module 3 and can be used to quickly familiarise staff, QPs and consultants with a product (as well as to refresh one’s memory!)


Section 3.2.P.2.6 of the CTD is only applicable if reconstitution diluents or dosage devices are required to administer the product. Information on the compatibility of the drug product with any diluents or devices (e.g. precipitation, sorption, stability) should be provided. Compatibility with excipients and the container closure system is tackled elsewhere.

Reduced testing of starting materials

Reduced or skip-lot testing of starting materials (APIs, excipients and packaging materials) is fully covered by EU GMP and is not product-specific. Therefore, in the relevant specifications in the MA application you should not include any reference at all to reduced testing on receipt by the finished product manufacturer. CMC assessors will object if you do.

Finished product assay limits

Finished product assay limits at release of ±5% are acceptable in the EU without further justification. Wider limits (even if based on pharmacopoeial monographs) have to be soundly justified based on production variability, the analytical test procedure, stability data and other relevant considerations. This differs from the North American norm, where assay limits at release are typically ±10%.

Ingredients in the eAF

When preparing to submit a European MAA, make sure that the dropdown lists in the eAF include all the ingredients your formulation contains. If not, you will need to get in touch with EMA in advance to get the ingredient included in the lists. So don’t leave it till the last minute.

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