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ARGOM Appendix 1: Guidelines on efficacy and safety aspects of OTC applications

Version 1.0

29 November 2015

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10. Modified release products

Modified release oral dosage forms (as defined in the Therapeutic Goods Order (TGO) 78 Standard for tablets and capsules) may be appropriate where:

  • the active ingredient has rapid absorption and elimination (e.g. half-life of less than 6 to 8 hours) associated with a correspondingly rapid loss of clinical effect;
  • the site of absorption is not confined to a limited region of the gastrointestinal tract;
  • the product is intended for use in conditions of sufficient duration to warrant the use of a sustained release formulation; and
  • the product is able to provide therapeutically effective doses of the active ingredient throughout the dosage interval.

Applications for registration of modified release formulations must be accompanied by evidence to demonstrate that ‘dose-dumping’ does not occur and that the product meets controlled release claims. The evidence should include clinical data to demonstrate the product’s bioavailability and pharmacokinetics.

Generally, the following bioavailability studies would be appropriate, depending on the product type:

  • studies comparing a single dose of the modified release product with a registered conventional release product;
  • studies comparing the steady state profile of the modified release product under the proposed dosage regime with that of a registered conventional release product under the approved dosage regime; and
  • studies comparing a single dose of the modified release product taken in a fasted state with the same product taken with food (preferably a high fat meal).

In some circumstances, bioavailability studies comparing the proposed formulation with an already registered modified release product may be appropriate, either in addition to the comparison with a conventional release product, or instead of these studies.

Where it is believed that a particular application warrants a departure from this guideline, a full justification for the departure should be submitted with the application. If the justification is not accepted, studies as above will be required.

Further information on data requirements can be found in the CPMP guideline document Note for guidance on modified release and transdermal dosage forms: Section II (Pharmacokinetics and Clinical Evaluation) (CPMP/EWP/280/96).

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