Introduction

The accessibility of both biologic and biosimilar medicines has changed the landscape of the Australian healthcare system. The majority of biologics drugs are used in the treatment of chronic diseases that generally occur in an aging population. In 2014, according to a National Health survey conducted by the Australian Institute of Human Welfare (AIHW) over 50% of Australians reported 1 of 8 chronic disease conditions in their lifetime (including cardiovascular disease, cancer, pulmonary diseases, diabetes, mental disorders, musculoskeletal diseases, chronic kidney diseases and oral diseases).

Key regulatory bodies and advisory groups in Australia

Biologics are the fastest-growing expenditure of the Pharmaceutical Benefits Scheme (PBS) in Australia. The PBS began as a limited scheme in 1948. It is an Australian government program that benefits all Australians by subsidising medicines to make them more affordable. In 2015-16 Australian government expenditure on biologics through the PBS was estimated at AU$2.29 billion. If biosimilar versions of these medicines had been listed on the PBS during that time, an estimated AU$367 million could have been saved by the goverment. Recognising the growing role of biosimilar medicines, the government has launched an initiative aimed at improving awareness and confidence in biosimilar medicines amongst prescribers, pharmacists and patients in Australia, known as ‘biosimilar uptake drivers’.

In the 2017 budget process, the Australian government reached an agreement for the initiation of ‘biosimilar uptake drivers’ with several key industry leaders. These leaders included the Generic and Biosimilar Medicines Association (GBMA, representing the generic and biosimilar medicines suppliers in Australia), Medicines Australia (a pharmaceutical community in Australia that assist in policy engagement and administer a ‘code of conduct’ for ethical marketing), and the Pharmacy Guild of Australia (a national employers’ organisation representing and promoting community pharmacies in the Australian healthcare system). Two key inititivates have since been implemented: encouraging biosimilar brand prescriptions over the reference biologics, and providing an efficient approval process for prescribing biosimilar brands. The GBMA supports the Australian government’s commitment of AU$20 million over 2015-18 for a biosimilars education and awareness initiative. However, education can only go so far in driving acceptance and uptake of biosimilars.

Currently, the GBMA is working with the PBS to support the long-term sustainability of the scheme by ensuring the timely and cost-effective provision of generic and biosimilar medicines to consumers. Due to the marketing approval requirements for generic and biosimilar medicines, these are often priced at a much lower cost (compared to the innovator drug). This means any drug prescriptions provided under the Australian healthcare system that can be changed from a biologic to a biosimilar product, will reduce the overall economic strain on the healthcare system and government budgets. However, there are concerns about ‘interchangeability’ from patients and healthcare professionals between biosimilar drugs and their biologic reference product, as they are not considered to be identical.

In Australia, before any drug can be registered with the PBS it is first approved by a licensing body, the Therapeutic Goods and Administration (TGA). The TGA is a government body established in 1989, which operates under a national legislative framework, evaluating drugs for safety and efficacy and their licensed use in Australia. On 16 December 2015 the TGA released updated guidelines on biosimilars in a ‘Regulation of biosimilar medicines v2.0 Dec’, referencing several European Medicines Agency (EMA) guidelines which disclose standards of quality, non-clinical and clinical data requirements for the similarity between biologics and biosimilars.

Biosimilar approvals in Australia

As per ‘Biosimilar medicines regulation, version 2.2, April 2018’, before a biosimilar medicine can be registered in Australia, clinical studies need to be performed to demonstrate the biosimilarity of the biosimilar to the reference biologic medicine already registered in Australia. The reference medicine must:

1. be a biologic that has been registered in Australia based on full quality, safety and efficacy data (‘the Australian reference medicine’)
2. have been marketed in Australia for a significant period and have a capacity of marketed use so that there is a significant body of data regarding the safety and efficacy for the approved indications.

Under the current legislation, the TGA cannot begin to evaluate a biosimilar application during the five-year data protection period. This data exclusivity period (protection of any drug clinical data submitted to the TGA for market approval) is completely independent of patent rights and is granted at the time of market approval of a drug product. In the interest of transparency, the TGA have disclosed timelines for the approval of new chemical entities (which biologics fall under) and generic medicines (which biosimilars fall under). The TGA aims to commence the evaluation of generic applications within 8.5 months and indicates that the pre-submission process takes about 3.5 months. Additionally, the TGA aims to complete the evaluation of an application within 255 working days after the application has been accepted. The result of this is a delay in approval for biosimilars, which means that a biosimilar version of a reference product may not be approved until 6-8 years after the market authorisation of the biologic reference product. The period of data exclusivity is often discussed and with biologics taking longer periods of time to develop, innovators have often argued that longer periods of data exclusivity are required to recoup their investments. In Australia, a five-year data exclusivity provision is provided for all new chemical entities, with no additional drug protection rights given to biologic drugs. The Australian Trade Minister, Andrew Robb, has stated that Australia would not agree to any Trans-Pacific Partnership (TPP) provision that would undermine the PBS or go beyond the provisions of the Australia–US Free Trade Agreement, and this would mean holding the five years of data protection. Furthermore, Australia does not provide any market exclusivity provisions, which would normally extend the period of time preventing generic or biosimilar drugs from entering the market.

Issues facing biosimilars

As biosimilar drugs are not considered to be identical to their biologic reference product, there is confusion surrounding what can be substituted when it comes to prescribing medicines. Drug substitution is recommended by the government-appointed Pharmaceuticals Benefits Advisory Committee (PBAC; an independent committee comprising of health professionals, health economists and consumer representatives) after the TGA has determined that a medicine is comparable to the reference medicine. Determinations are reliant on government authorities evaluating data and providing a recommendation on whether the biosimilar is similar enough to the biologic. If not, additional clinical and preclinical data is requested or the application is rejected.

Discussions continue regarding how to distinguish a biosimilar from a biologic reference product - biosimilar naming conventions are an important topic when considering interchangability of a prescribed drug product. With small molecule drugs, the generic version adopts the International Nonproprietary Name (INN), which is published by the WHO, however, this is not the case for biosimilar drugs. In July 2013, the TGA published guidance on biosimilar naming based upon the combination of a WHO programme on INN-issued biosimilar identifiers with the Australian Biological Name. Since then, the WHO have published revisions of their policy, triggering the TGA to evaluate their own processes. The TGA, in July 2017, sought comments from interested parties on additional naming requirements for biologic medicines as a way of strengthening traceability and pharmacovigilance. TGA has proposed four options for the public to comment on:

1. No change to the current system
2. Keep the current system, but with activities that increase public reporting of adverse events with the inclusion of the product’s trade name, AUST R (Australia Registered) and batch number
3. Move towards adopting a barcode system similar to Europe
4. Introduce the use of suffixes to the naming of biologics – in a similar way to the system implemented in the US

This consultation closed in September 2017, and the TGA is yet to decide the rules for naming a biosimilar.

Another issue facing biosimilars is understanding when a drug product can be substituted by a health professional. In April 2015, the PBAC established ‘bioequivalence flags’ (also known as a-flagging) on a case-by-case basis for biosimilars, which allowed biosimilars that were marked with an ‘a-flag’ to be determined as equivalent, and therefore suitable for substitution at the pharmacy level. On 26 May 2015, Australian Health Minister, Sussan Ley, announced that Australia would become the first nation in the world to allow so-called “automatic” substitution of biosimilars by pharmacists in place of the biologic prescribed by a physician. Since then, the PBS has implemented a new system called ‘brand substitution groups’. This system also uses an ‘a’ and ‘b’ flagging system, but takes into account the TPP when it considers substitutable products.

Conclusion

The TGA has approved multiple biosimilars for use in Australia, including human growth hormones, granulocyte colony-stimulating factors, insulins, erythropoietin, monoclonal antibodies and tumour necrosis factor inhibitors.

Biologics are a continually growing expense on the healthcare system and by encouraging biologic to biosimilar drug substitution, this can amount to tens of millions of dollars saved every year on just a single product. When a biosimilar product is listed on the PBS and becomes subsidised by the government, it automatically triggers a 16% price reduction on all versions of the product as stated by the PBS. According to the GBMA, there is a potential AU$2.6 billion market for biosimilars per year; this may be due to multiple blockbuster biologics losing patent protection in the next 10 years.

While the biologic/biosimilar landscape continues to be difficult to navigate for biotech companies, the Australian goverment are attempting to provide transparency for patients and are streamlining prescription processes, by pushing forth the ‘biosimilar uptake drivers’ policy. These key initiatives work with regulatory bodies, advisory bodies, patients and healthcare professionals, meaning that when biosimilars are approved by the TGA there is a high chance they will be prescribed to patients.

Register to the INNsight Newsletter for regular updates on patent intelligence.