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17 Aug 2015

In June, the Australian Parliament passed legislation allowing prescribed biological medicines to be substituted with biosimilar drugs when they are dispensed by pharmacists.

Under the change, the Pharmaceutical Benefits Advisory Committee (PBAC) will assess on a case-by-case basis whether a specific biological medicine can be safely switched for a biosimilar by a pharmacist. As for all prescribed medicines, doctors can still control what medicine is dispensed to their patients by marking ‘do not substitute’ on the prescription.

Is pharmacist substitution of biologicals a good thing? Or will this pose risks to patient health? And what are biological and biosimilar medicines anyway?

The AMA is satisfied with the regulatory arrangements introduced for biosimilars, but it is important that doctors are aware of the potential implications for their patients. Here’s a summary of the key facts.

What are biologicals?

A biological medicine is made from a living organism, typically extracted from a human cell or tissue-based system. Biologicals include:

  • hormones used to treat hormone deficiencies, e.g. insulin for diabetes;
  • monoclonal antibodies for the treatment of autoimmune diseases and cancers;
  • blood products, e.g. for the treatment of haemophilia;
  • immunomodulators, e.g. beta-interferon for multiple sclerosis;
  • enzymes, e.g. to remove blood clots; and
  • vaccines to prevent a number of diseases.

The manufacturing process for biologicals is complex and sensitive to variations because of the nature of the biological substances used and modified. Subtle variations of a biological substance exist between batch preparations from the same manufacturer.

What is a biosimilar?

A biosimilar is not a generic biological medicine.

A biosimilar medicine is highly similar to a biological medicine that has already been approved but for which the patent has expired. Unlike a generic medicine, which is made from the same chemical compounds and has the same chemical structure as the original brand medicine, a biosimilar is not a generic copy of the reference biological medicine.

While a biosimilar’s manufacture is based on the same active ingredient as the original biological, by their nature they cannot be identical.

Before a biosimilar can be approved for sale in Australia, any differences between the biosimilar and its reference medicine must have been shown not to affect quality, safety or efficacy through a robust clinical trial process.

Biosimilars, like generic medicines, will be significantly cheaper than the original biological medicine, although not to the same extent given the higher costs needed to invest in clinical trials, manufacturing and post-approval monitoring programs.

There are already biosimilar versions of medicines listed on the Pharmaceutical Benefits Scheme (PBS) being prescribed to patients.

What are the issues?

Biologicals are more likely to cause an immune reaction than chemical medicines.

In turn, small changes in the manufacturing process or composition of a biological may result in the emergence of immune reactions, even if the agent had previously been well tolerated. For example, in one instance a minor alteration in the manufacturing process of erythropoietin alpha triggered acquired pure red blood cell aplasia in a small cohort of patients.

It is therefore important that effective adverse event reporting mechanisms are in place to ensure that any patterns of adverse events are quickly identified and tracked to the specific biological brand.

Because of the documented variability between biologicals and biosimilars, it is conceivable that adverse reactions may increase with substitution.

Some consumer groups and pharmaceutical companies have argued that allowing biologicals to be switched at the dispensing point will make it more difficult to identify the specific brand if an adverse event occurs.

Government regulation

The Therapeutic Goods Administration (TGA) will remain the regulatory body responsible for assessing and approving a biosimilar as a safe and equally effective treatment compared to another medicine before it can be sold in Australia. The TGA is currently reviewing its assessment guidelines.

Once the biosimilar has been approved by the TGA, the PBAC will also consider if the biosimilar medicine should be listed to allow substitution by a pharmacist under the PBS.

The PBAC has stated that it will not recommend a biosimilar as suitable for substitution unless it is sure of its equal safety and effectiveness.

The PBAC’s assessment will include consideration of whether there is available data to support safe switching between the original product and the biosimilar product, and whether it can be safely substituted by a pharmacist at the point of dispensing.

Examples of biosimilar brands available in Australia include:

  • Aczicrit, Grandicrit and Novicrit with the active substance epoetin lambda – all have been approved by the TGA but only Novicrit is listed on the PBS; and
  • Nivestim, Tevagrastim and Zarzio with the active substance filgrastim – all have been approved by the TGA and all are listed on the PBS.

No biosimilar has yet been approved for substitution by a pharmacist.

What should doctors do?

  • When prescribing biological medicines, doctors should ensure they mark the prescription as ‘do not substitute’ if they have any concerns about the impact on their patients of switching to another brand;
  • doctors should discuss this decision with their patients so that patients are also aware they must not allow their pharmacist to substitute the medicine;
  • doctors who find out that a pharmacist has substituted a medicine ignoring the ‘do not substitute’ mark on the prescription should report the behaviour. Under PBS related legislation, this can attract a $2000 fine or 12 months in gaol. Report breaches to the Department of Human Services by phoning 131 524 or filling out an online form at;
  • Any suspected adverse event should be reported to the TGA:

The AMA welcomes members’ views on this issue to Member comments help inform AMA advice and activities.


Published: 17 Aug 2015