The first challenge with understanding the regulation of biosimilars is to recognise the broad array of terminology which is used i.e.

  • Similar Biological Medicinal Product (SBMP) (the term used by the European Union);
  • Follow On Biological (the term initially used by the FDA);
  • Subsequent Entry Biologics (the term used by Health Canada);
  • Similar Biotherapeutic Product (the term used by the WHO).

The one term which is not favoured, due to its inaccuracy, is generic biological medicine or biogeneric. Given the nature of biological medicines (i.e. complex molecules which have microheterogeneity in terms of structure) it is not possible to manufacture an identical molecule to that of the innovator; the best case scenario is that the molecule is similar.

Within Australia the terms biosimilar and SBMP are used by the Therapeutic Goods Administration (TGA). The TGA released a guidance document entitled the ‘Evaluation of biosimilars‘ in July 2013 and this document is currently under review.

Biosimilars follow the same registration process as that of prescription medicines. An abridged data set, in the Common Technical Document (CTD) format, can be submitted for registration of a biosimilar in Australia. Whilst the package can be abbreviated it still contains a significant amount of data including both non-clinical and clinical studies.  This is necessary in order to be able to contest that the biosimilar in sufficiently similar to the reference product. Consequently a comparability to the originator molecule (reference product) as registered in Australia is submitted to the TGA in support of the registration application. Additionally a Risk Management Plan (RMP) is required for inclusion in SBMP submissions.

A critical decision in the development of a biosimilar is the choice of the reference product. It is necessary to use the same reference product for the comparability exercise for the Drug Substance and the Drug Product (Module 3) and also for all the testing conducted in the non-clinical (Module 4) and clinical (Module 5). Additionally the biosimilar should have the same formulation, strength and dosage form as that of the reference product. The reference product should be registered in Australia, be the innovator product (not a biosimilar) and have been on the market for sufficient duration that any adverse effects have had sufficient time to become apparent. A reference product can be sourced from overseas on the proviso that it is registered in Australia and that comparative studies have been conducted between the overseas manufactured product and that sourced in Australia i.e. bridging comparability studies. These bridging studies may potentially be abridged if it can be proven that the product sourced overseas and supplied in Australia are manufactured in the same facility.

Overall the process of developing a registering a biosimilar is considerable more involved and extensive than that of a generic chemical entity due to the complexities and variability of the biological molecule. Given that the TGA guidance on biosimilars in currently under review, early communication with the TGA is recommended.