ADEC PSC 109th meeting recommendations

Ratified recommendations of the 109th (2006/4) meeting of the Pharmaceutical Subcommittee (PSC) of the Australian Drug Evaluation Committee (ADEC) held 24 July 2006

The PSC resolved to advise the ADEC that:

Provision of an Absolute Bioavailability Study for all New Chemical Entities

Recommendation No 1866

The PSC observes that several recent applications to register new chemical entities have not included the expected full pharmacokinetic characterisation. While relevant studies will depend on the drug, dosage form and indication, direct studies in patient subgroups (e.g. renally or hepatically impaired patients) are normally appropriate. Population pharmacokinetic analyses are useful, but do not constitute an adequate substitute for the key, direct pharmacokinetic studies.

The PSC is concerned that many recent applications do not include any absolute bioavailability study. The PSC fully supports the Australian Regulatory Guidelines for Prescription Medicines which state that absolute bioavailability should be established (ARGPM Appendix 15.3). This is also in keeping with overseas guidelines (e.g. CPMP/EWP/QWP/1401/98 Note for Guidance on the Investigation of Bioavailability and Bioequivalence). The Committee does not consider that low aqueous solubility constitutes a justification for not undertaking an absolute bioavailability study given that suitable formulations using additives or non-aqueous solvents are now well established. In some cases it may be appropriate to use a low intravenous dose. As investigative formulations can be prepared immediately before use, solution stability problems should also not preclude a study.

The PSC recommends that the TGA brings to the attention of Sponsors the importance of full pharmacokinetic characterisation of new chemical entities.