The Pharmaceutical Benefits Advisory Committee and the Therapeutic Goods Administration have been urged to clarify their policies around “biosimilars” – drugs which act in the same way as patented biological drugs, although they may not be exactly the same.

Dr Ruth Lopert, who was the TGA’s Principal Medical Adviser from 2008-2011 and Director of the Pharmaceutical Policy Taskforce in the Department of Health in 2005-06, explains some of the complexities for regulators and consumers raised by biosimilar products.


Switching, interchangeability, substitution: TGA and PBAC confusion over biosimilar policy and nomenclature

Ruth Lopert writes:

Despite several biosimilar products already approved by the TGA and available in Australia, there is ongoing confusion over biosimilar funding policy.

TGA is currently revising its position on the evaluation and nomenclature of biosimilars, and PBAC recently released two statements regarding the potential for biosimilar substitution at pharmacy (see here).

Unfortunately, neither of the PBAC’s statements provides adequate clarity as to its position or processes, and both are causing concern among patient and provider groups.

There is clearly a great deal at stake. Previously substitution at pharmacy has been critical to the ability of small molecule generics to gain market share.

The problem with biosimilars is that unlike generic versions of small molecule medicines, they cannot be declared to be bioequivalent by the TGA – bioequivalence previously being an implied pre-requisite for ‘A’ flagging by PBAC.

Because biologics – products biotechnologically derived from living organisms – are by their nature invariably complex, and can be exquisitely sensitive to even minor changes in manufacturing processes – the assessment of a biosimilar product is both more extensive and more complex than a small molecule generic.

A key issue in determining biosimilarity is assessing comparability in safety and efficacy, as well as in immunogenicity – the capacity to induce an immune-mediated response, which could, for example, lead to reduced efficacy through the production of neutralizing antibodies, or lead to the development of more serious effects impacting the safety of the product.

PBAC’s first statement dated April 2015, caused widespread concern as it stated the Committee’s default position would be that:

“…biosimilar products would be “a” flagged, and therefore suitable for substitution at the pharmacy level, where the data are supportive of this conclusion.. (and that)  relevant considerations in establishing that a biosimilar product could be “a” flagged  (would include ) ..(A)bsence of data to suggest significant differences in clinical … effectiveness or safety compared with the originator product;… (and)… (A) vailability of data to support switching between the originator product and the biosimilar product…”

But of course absence of evidence isn’t evidence of absence.

In an attempt to clarify its position, the PBAC issue a second statement on June 18th saying: 

“..if the biosimilar is approved by the Therapeutic Goods Administration as a safe and equally effective treatment compared to another drug, the PBAC will then consider listing the biosimilar drug on the PBS. During this assessment process, the PBAC will also consider whether the biosimilar drug should be listed to allow substitution by a doctor or pharmacist. This will be done on a case by case basis.”

Unfortunately, neither statement identifies the nature of the evidence required to support substitution, nor which entity will be responsible for evaluating it.

What’s now needed is statement from the TGA as to whether (and if so, how) it is planning to assess (and presumably assert, if satisfied) the safety of repeat switching.

PBAC should also issue a further statement distinguishing between interchangeability at the point of first prescription vs substitution on repeat dispensing.

For a product deemed biosimilar by the TGA there should be clinical equipoise about the choice between a biosimilar or originator product at treatment initiation – and therefore there could also be discretion at the point of dispensing unless explicitly precluded by the prescriber.

However, unless there is adequate evidence of the safety of repeat switching, the initially dispensed product should continue to be the one dispensed when a repeat prescription is presented. This could perhaps be denoted by a different flag in the PBS Schedule.

There’s as yet no consensus internationally on standards for assessing the safety of repeat switching – which is of particular relevance to monoclonal antibodies.

Notwithstanding the fact that concerns about the immunogenicity of repeat switching are largely theoretical, confidence in product safety should arguably should be the prerequisite for substitution at pharmacy and the designation of an “a” flag.

• Ruth Lopert is currently based in Washington DC where she is Deputy Director, Pharmaceutical Policy & Strategy at Management Sciences for Health, and an adjunct professor in the Department of Health Policy & Management at George Washington University. She was TGA’s Principal Medical Adviser from 2008-2011 and Director of the Pharmaceutical Policy Taskforce in DoH in 2005-06.


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