EMA Acts To Stem Conflicts Over Generic Drug Dissolution Specs

In an effort to harmonize assessments among the regulatory agencies of the European Union's member states, the European Medicines Agency May 13 issued a draft reflection paper on the dissolution specification for generic oral immediate release drug products.

Disagreements among EU member state regulators over the suitability of dissolution specifications have led some to refer generic drug applications to the EU's Coordination Group for Mutual Recognition and Decentralized Procedures – Human, or CMDh, for resolution.

Such disagreements arise when a member state declines to approve the reference member state's assessment report of a drug application on the grounds of potential serious risk to public health. If member states cannot reach consensus through CMDh procedures, the matter is referred to EMA for arbitration.

The draft reflection paper guides generics firms on best practices for establishing dissolution specifications for immediate release oral drug products. The document notes that some drug products require case-by-case evaluation, such as those with narrow therapeutic indices or with critical dissolution behavior, as with sublingual or orodispersible tablets that have some buccal absorption.

Although the draft reflection paper does not directly affect brand firms, it does rely on scientific principles that could be extrapolated to new drug products.

The dissolution specifications, which say what percent of active substance should be released by a specified time point, allow generics firms to extrapolate results of bioequivalence studies to commercial batches by establishing routine batch control test conditions.

An annex to the draft reflecting paper provides a decision tree for setting specifications based on the dissolution results of the bioequivalence batch.

Email comments on the draft reflection paper to [email protected] by Aug. 13. Be sure to use EMA's comment template.