September 2022
Real CMC Tips and Insights

published 4 Oct 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 September 2022 are collected here, for convenience. Make sure you follow  Real Regulatory Ltd and Real CMC for regulatory news, reports and hints.


EMA Training Materials

Recordings and/or presentations from EMA workshops are generally available on the EMA website for years following the event, providing a wealth of information and training materials. Some of the CMC-relevant workshops on the website are the ones on biopharmaceuticals, development for paediatric use, ICH Q3D, and many more.


When is an Excipient Novel?

A novel excipient is a new or well-established chemical entity being used for the first time in a drug product or by a new route of administration. When determining if an excipient is novel or not, consider use throughout the ICH regions. European competent authorities have been known to regard excipients as non-novel when used extensively in ICH regions other than Europe.


IMPDs for Small Molecule Drugs

For Phase I studies, stability data on the IMP need not be available at clinical trial application stage. However, the assigned shelf-life must be justified, studies under accelerated and long-term conditions initiated before study start, and an ongoing stability program performed with the relevant batches. For Phase II and III studies, stability data at accelerated and long-term conditions must be submitted for evaluation in the IMPD.


Leaching and Sorption

Interaction studies identify any unacceptable effects of packaging materials and drug substance/product on each other. In Europe, interaction studies might be required for solid drug products intended for inhalation, parenteral or ophthalmic administration but not other solids. Migration studies are needed for non-solid drug substances and drug products whenever extraction studies have identified the presence of one or more extractables. Sorption studies are needed for non-solid drug products when changes observed during stability studies might be due to interaction with packaging materials


Dissolution Limits for Generic SODs

When selecting biobatches, bear in mind that the future dissolution specification for your product will be tied to the dissolution results for the biobatches. Typically, you will not be allowed to set a Q value that differs by >10% from the biobatch dissolution result (the mean value of 12 units dissolved in 15, 30 or 45 minutes, depending on how quickly your formulation reaches 85% dissolution). The minimum acceptable Q for a single point dissolution test is 75% at 45 minutes. Assessors will not accept justifications claiming that a specification is too tight to comply regularly with S1 because consistent compliance with S2 is perfectly acceptable.



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