Regulatory aspects of modified release dosage forms: clinical studies.

In a recently drafted "Note for guidance" of the European Community it is stated that "The therapeutic objective and rationale for developing the prolonged release product should be provided". This implies that any therapeutic claim should be documented by ad hoc clinical trials. Another "Note for guidance" describes "the studies to be conducted in man, which are specific to new extended release forms containing recognized active and safe medicinal substances so as to ensure a more prolonged action than the conventional pharmaceutical forms already marketed". From this second "Note for guidance" it appears clearly that three situations must be distinguished: a) a modified release dosage form is intended for use with a new active principle; b) the active principle is already available in a conventional pharmaceutical form; and c) the active principle is available as a modified release dosage form with which the new form is not bioequivalent. In case a) drug development clearly proceeds as with any other new clinical entity, but in addition "the therapeutic objectives and rationale for developing" a prolonged release product must be provided. Unless the reasons appear evident, some forms of comparison with a conventional release form or a solution will probably be needed for marketing authorization to be granted. In case b), recommendations contained in the "Note for Guidance" on clinical testing will have to be followed. For case c) no clear recommendations are available and it would probably be more efficacious to develop a new and bioequivalent modified release dosage form rather than to embark into a full clinical program.(ABSTRACT TRUNCATED AT 250 WORDS)