June 2021
Real CMC Tips and Insights

published 2 Jul 2021

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 June 2021 are collected here, for convenience. Make sure you follow  Real Regulatory Ltd and Real CMC for regulatory news, reports and hints.

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.


Extraction studies identify the possible presence of extractables in packaging materials. In Europe, extraction studies are not required for solid drug substances and solid drug products. For non-solids, studies are not needed for plastic packaging materials described in the Ph. Eur. or in the pharmacopoeia of an EU member state. If the drug product is not intended for inhalation, parenteral or ophthalmic administration, approval of plastic packaging materials for use in food packaging suffices in lieu of pharmacopoeial compliance.

Biowaivers for SODs

For solid oral dosage forms, biowaivers for additional strengths are possible if the qualitative composition and manufacturing process are the same, the strengths are quantitatively proportional (excluding coating components, capsule shells, colours and flavours), and supportive in vitro dissolution data are available. If the drug substance constitutes less than 5% of tablet core weight, some deviation from quantitative proportionality is permitted. Each layer of bilayer tablets is considered independently. Fixed combinations are more complicated, therefore detailed worked examples have been provided by the PKWP in Q&A 6.4

Drug Substance Specifications

The applicant's specification for a drug substance presented in the MA dossier should match that of the ASMF or CEP holder, unless certain tests can justifiably be omitted e.g. superfluous tests or limits that are too tight. The applicant's specification may include additional tests, if critical to the quality of the drug product e.g. bacterial endotoxins. If there is more than one drug substance supplier, the applicant's specification for the substance should consolidate the various sets of specifications.


For previous monthly round-ups, you can follow these links:

May 2021 Real CMC Tips & Insights Round-Up:

March 2021 Real CMC Tips & Insights Round-Up:

February 2021 Real CMC Tips & Insights Round-Up:

January 2021 Real CMC Tips & Insights Round-Up:

December 2020 Real CMC Tips & Insights Round-Up:

November 2020 Real CMC Tips & Insights Round-Up:

October 2020 Real CMC Tips & Insights Round-Up:

September 2020 Real CMC Tips & Insights Round-Up:

August 2020 Real CMC Tips & Insights Round-Up:

July 2020 Real CMC Tips & Insights Round-Up:   

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