What are biosimilars?

A medicine made from living organisms, such as protein, bacteria or yeast, is known as a biological medicine.

Since the 1980s, hundreds of biological medicines have been approved for the treatment of diseases such as cancers, diabetes, heart attacks, rheumatoid arthritis, Crohn’s disease and many more.

Around 300 new biological medicines are currently under development for the treatment of cancer and related conditions.

A biosimilar medicine is a very similar version of an already-approved biological medicine, in terms of its characteristics, quality, safety and efficacy.

A biosimilar medicine is not considered a generic medicine, as it is virtually impossible to make an exact copy of a living organism.

However, much like generics, biosimilar medicines are also based on original medicines that have reached the end of their patents.

Biosimilar medicines are developed to increase treatment options, and can usually be produced at a lower cost than the original biological medicine.

How biological and biosimilar medicines work

Unlike traditional chemical medicines which are made by combining chemical ingredients, biological and biosimilar medicines are made from living organisms.

Biological medicines usually have more complex and larger structures than their traditional counterparts.

For example, Aspirin, a chemical medicine, contains 21 atoms, while a biological medicine may contain more than 20,000 atoms.

As a result, biological medicines are more sensitive and are more likely to cause an immune reaction in the body than chemical medicines.

Once administered, a biological medicine can mimic the natural protein in a patient, thereby helping to reduce symptoms and slow the progression of a disease. Biological medicines, such as vaccines, can also prevent disease.

Biological, and biosimilar, medicines are often administered by injection or infusion, whereas chemical medicines are usually taken as a tablet or capsule.

Many traditional medicines can be self-administered, but biological medicines are often administered in hospital as an injection or with the assistance of medical staff.

Biosimilar FAQs

Once a product patent expires, manufacturers are legally allowed to develop a generic version of a chemical product, or a biosimilar version of a biological product.

While it’s relatively easy to manufacture an exact generic copy of a simple chemical structure, it’s almost impossible to make an exact copy of a living organism.

Therefore, if someone is talking about a generic medicine, they are referring to the exact copy of a traditional chemical medicine that is no longer under patent.

A biosimilar, on the other hand, refers to a highly similar but not identical version of a biological medicine.

There are three main reasons why it is virtually impossible for different manufacturers to replicate a biological medicine:

  • As living organisms, there will always be some differences between medicines even if this does not affect how the medicine works
  • The structures are large and complex, making it difficult to create an exact copy
  • The final medicine is highly dependent on the manufacturing process, and once the original patent for a medicine expires each manufacturer has to make their own decisions around the cell lines, conditions to grow the cells, stabilising compounds to use, as well as how the medicine is packaged and stored.

Substitution

If two or more medicines are considered substitutable, the pharmacist may dispense either of these medicines from the script, provided the prescriber (i.e. GP or specialist) has not indicated ‘brand substitution not permitted’, and they have permission from the patient.

This applies most often to generic medicines and biological medicines with a biosimilar that has been recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) as substitutable.

Substitutable medicines are marked in the Schedule of Pharmaceutical Benefits with an ‘a’ (a-flagged).

It is important that the prescriber of the biologic is notified of the switch. This allows for appropriate monitoring of a patient’s response to treatment , as well as tracking of adverse events.

Interchangeability

If two or more medicines are considered interchangeable, the prescriber (i.e. GP or specialist) may choose to prescribe either of the medicines for a patient to treat the same condition; however, the pharmacist must dispense as prescribed. This generally occurs between two different medicines, rather than brands or biosimilars of the same medicine.

In 2017, the US Food and Drug Administration (FDA) issued draft guidance detailing the agency’s expectations for demonstrating biosimilar interchangeability.

To be approved as interchangeable, it must demonstrate that it ‘can be expected to produce the same clinical result as the reference product in any given patient’ when substituted, and ‘the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.’

Switching

Switching between medicine brands could occur in either case.

One would be at the direction of the prescriber (prescribing an interchangeable medicine), the other would occur at the pharmacy level (brand substitution).

As part of the 2017 Budget process the Government reached agreement with Medicines Australia, the Generic and Biosimilar Medicines Association and the Pharmacy Guild of Australia to implement biosimilar uptake drivers.

Two specific biosimilar uptake drivers are being implemented:

1. Encouraging prescribing of a biosimilar brand rather than the reference biological brand for treatment naïve patients.

For the purpose of this uptake driver a patient is ‘treatment naïve’ if they have not previously taken the biological medicine intended to be prescribed.

That is, they have not taken either the reference or biosimilar brand of the particular biological medicine.

Continued use of a biosimilar brand after it is first taken by a patient is a matter for the patient in consultation with their prescriber and pharmacist.

A patient is not treatment naïve if they took any brand of the particular biological medicine in the past, even if that treatment occurred some time ago.

2. Providing for a simpler and faster approval process for prescribing biosimilar brands (e.g. streamlined authority) while maintaining an existing higher level authority requirement for the reference biological brand (e.g. written authority).

There are three broad types of authority requirement for prescribing PBS medicines:

  • Written authority – the prescriber is required to obtain from the Department an authority approval in writing for prescribing the medicine.
  • Immediate authority – the prescriber can get the authority to prescribe either online or by phone (which can occur during a consultation).
  • Streamlined authority – if the prescriber is satisfied that the specific eligibility criteria and rules for prescribing on the PBS are met, they mark a ‘streamlined authority code’ on the prescription. A ‘streamlined authority’ provides the simplest and fastest method for demonstrating authority to prescribe the medicine.

In the public hospital setting, brand decisions are made by clinician-led committees on behalf of doctors and patients.

In Australia, there is no current mandated requirement for GPs, pharmacists or patients to use biosimilar medicines.

By way of contrast, the Government of Alberta (Canada) has announced that it will begin forcibly switching 26,000 patients from their physician-chosen biologic medicines to government-chosen biosimilars beginning 1 July 2020.

According to the Alliance for Safe Biologic Medicines (ASBM), only half of Albertan patients – those on public pharmacare plans – will be subject to the forced-switching policy.

Patients on private health plans, including Ministry of Health officials, will not be forced to switch. Children and pregnant women are also exempted.

On 27 May 2019 the Government of British Columbia (BC, Canada) announced 20,700 patients would be forcibly switched from their existing medicines to the government’s choice of preferred biosimilar products and cease the reimbursement of their current biologic medicine.

The policy disregards important scientific considerations for patients on biologic medicines and most alarmingly, eliminates patient choice, according to the Alliance for Safe Biologic Medicines (ASBM).

Biosimilar medicines and bowel cancer

There is a growing number of biosimilar medicines available in Australia, and some of these are relevant to cancer patients receiving chemotherapy (see below).

For example, the active substance known as epoetin lambda is used to treat anaemia in patients receiving chemotherapy for certain types of cancer.

The active substance known as filgrastim is used to help the body make new white blood cells following treatment with some types of chemotherapy.

Active ingredient Therapeutic area treated by active ingredient Biological Biosimilar Date of ARTG listing for biosimilar Date of PBS listing for biosimilar
Bevacizumab Metastatic bowel cancer Avastin Abevmy 06/09/2021 01/12/2022
Bevaciptin 02/11/2021 01/11/2022
Bevacip 02/11/2021  
Mvasi 30/06/2020 01/06/2021
Zirabev 21/11/2019  
Epoetin lambda Anaemia Eprex brand of epoetin alfa Novicrit 27/01/2010 01/08/2010 (pre-dated current PBAC approach to advice on ‘a’ flagging)
Filgrastim Chemotherapy induced neutropoenia Neupogen ‘a’ flagged Nivestim ‘a’ flagged 16/09/2010 01/04/2011
Tevagrastim 29/08/2011  
Zarzio ‘a’ flagged 07/05/2013 01/09/2013
Pegfilgrastim Stimulates the growth of ‘healthy’ white blood cells in the bone marrow, once chemotheraphy is given. Pegfilgrastim is a longer acting form of filgrastim Neulasta ‘a’ flagged Fulphila 17/08/2018 01/04/2020
Neutropeg 19/08/2019  
Pelgraz ‘a’ flagged 13/12/2019 01/08/2020
Ziextenzo 06/09/2019 01/03/2020

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