On 27 November 2014, the European Medicines Agency (“EMA”) published its new guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (the “Guidelines“).

Modified release dosage forms are formulations where the rate and/or site of release of the active ingredients are different from that of the immediate release dosage form administered by the same route.

The purpose of the new Guidelines is to define the studies necessary to investigate the efficacy, safety, biopharmaceutic and pharmacokinetic properties of modified release formulations. The Guidelines cover dosage forms administered orally, intramuscularly and subcutaneously and transdermally. They also set out general principles for designing, conducting and evaluating related studies.

The Guidelines provide that the development of a modified release formulation should be based on a well-defined clinical need, such as improvement in patient compliance and/or safety. They also stipulate that the dossier submitted in support of an application for marketing authorisation must provide a full justification of:

  • The physical form of the modified release device and the mechanism of the release form;
  • The choice of the dosage form, defining the in vitro and in vivo performance of the product;
  • The choice of active substance contents per unit of the dosage form;
  • The clinical rationale for the new dosage form, particularly in relation to the proposed indications and posology.

The precise type and number of studies required will be determined by the intrinsic properties of the active substance, the route of administration, the type of delivery system and the intended indication.

The Guidelines will come into effect on 1 June 2015 and will replace the EMA’s Guideline on Modified Release Oral and Transdermal Dosage Forms Section II.