New Thinking for New Science- Biopharmaceutical Patent Disputes in Australia

First published as: Pearce et al, ‘New Thinking for New Science – Biopharmaceutical Patent Disputes in Australia’ (2020) 120 Intellectual Property Forum 33.

As we consider the future of pharmaceuticals (“pharma”), we sharpen our focus on biologics in our near vision, and then through biologics to the cell and gene therapies on the horizon. The biosimilars boom is upon us, and for at least the foreseeable future, patent litigation will focus on disputes between originator and biosimilar entrants battling for post monopoly market share of these life changing medicines. Given the dearth of biopharmaceutical (“biopharma”) disputes to date, we must extrapolate from small molecule litigations into the world of large molecules to determine whether the significant differences in patent landscapes and market dynamics will result in gaps forming between the treatment of biopharma and pharma products by the courts. We say in Australia those gaps could be quite significant.

Patent landscape: an explosion of patents on the biopharma horizon

To understand the magnitude of the patent landscape for a biopharma product, it is useful to consider the difference between a small and large molecule-based product. The designation of “large” and “small” molecule products is meant to distinguish the active ingredient on the basis of size. However, these designations fail to truly convey the substantial difference in size of the active ingredients, particularly with respect to an antibody based product where the moniker “gargantuan molecule” appears more apt.

Roughly speaking, a large molecule biopharma product (e.g. an IgG antibody) may have a molecule weight around 150,000 daltons or more than 160 times larger than a small molecule, which is generally understood as having a molecule weight below 900 daltons. The complexity of the biopharma product is enhanced by the differences in manufacturing processes for the products. Whereas a small molecule is generally produced by a series of controlled synthetic steps, a large molecule biopharma active is usually produced as the product of a cellular process. Unlike a small molecule, a large molecule active, as a product of a cellular process, will generally not have a single structure. Rather, a biopharma active is generally a mixture of different structures, each of which must ultimately be characterised prior to regulatory approval. In the case of an antibody-based biopharma product, the cellular manufacturing processes may change the structures and/or identity of amino acids to produce different forms of a biopharma active. An example of this type of modification includes so called N- or C-terminal modifications. Another common modification of an antibody is glycosylation, which is the addition of complex sugars (known as glycans) to an antibody by the cellular machinery. The glycans added will be a mixture, adding to the complexity of forms in the biopharma active. All of these differences contribute to the massive patent landscape encompassing any biopharma product “large molecule product”.

To put it simply, there are very significant differences between the patent landscapes for large molecules (e.g. antibodies) and small molecules. Mostly, these differences are in scale and complexity.

Part of the scale difference can be attributed to what we call the “blockbuster effect”: the more successful a product is (large or small molecule), the greater the originator’s interest in (and budget for) patents. Because most of today’s “blockbusters” are biologics (10 of the top 15 products globally are biologics),[4] these products are very heavily patented. Some portion of the complexity difference is attributed to what we call the “gold rush effect”: because of the relative immaturity of biopharma industries we often see multiple interested parties scrambling for monopoly space, often resulting in overlapping and nested patents with multiple interested patentees. These effects are compounded by the complexity of the large molecule itself that directly impacts the complexity of the processes of making and purifying the large molecule, which dwarfs the complexity of processes involved in the manufacture of even the most complex small molecule.

For a small molecule medicine, the originator will typically seek to protect its product with claims directed to (consecutively):

• the active pharmaceutical ingredient (“API”);

• formulation comprising the API;

• processes of producing the API,

• methods of treatment (“MOT”),

• second medical uses; and

• various molecular forms of the API (such as different polymorphic forms).

In addition to (and subsequent to) originator patents in these categories, third parties (including generic companies) routinely seek coverage for, e.g. alternative processes of producing the API, alternative formulations, and alternative molecular forms.

While this landscape is by no means small, each of these categories of claims is substantially expanded for a biopharma product where many multiples of relevant patents are identified in freedom to operate (“FTO”) searches.

Biopharma patent landscapes dwarf those of small molecules.  For biopharma products, the types of relevant patents are the same as small molecules, however the size and complexity of the patent landscape for a large molecule differs considerably from a small molecule, and is compounded by the blockbuster effect, the goldrush effect, and the process complexity. For example, a general keyword search, which would be considered a rather narrow search, for the terms “anti-VEGF” and “antibody” in claims identifies in the order of 840 patent families.[5]  Searching a particular anti-VEGF antibody, for example “bevacizumab”, identifies in the order of 2,700 patent families.[6] The same type of key word search for a small molecule API, for example “esomeprazole”, identifies approximately 620 patent families.[7]

API claims to the active in the biopharma product (e.g. an antibody) may be devoid of any structural limitations and rather define an interaction with a biological target, which is usually the case for newly discovered biological targets. Such functional patent claims encompass any later discovered biologic directed at the same target, and block both independently developed biologics as well as any potential later biosimilars.[8] Broad functional based API patents are usually followed by patents with claims directed to a specific biologic, which in the case of an antibody may relate to small pieces (sequences) of the antibody structure. The later sequence-based patents may also include claims describing the binding site of the biologic on the biological target. These binding-site defined claims are a second class of functional claims with the potential to encompass not only a later biosimilar but any contemporaneous or later “originator” biologic binding the same region of the biological target. In view of both sequence-based and function-based claiming, a biosimilar developer may face more than one “originator” patent directed to the active biologic.

The methods of producing a biopharma product are also an exceptionally fertile ground of patent protection. As producing a biopharma product requires harnessing a living cell and growing the cells, process patents are directed at the numerous molecular biology techniques relating to the cells that produce the biologic, the methods and tools developed to instruct the cell to make the biologic as well as the methods and media required to grow the cells. While process patents specific to an originator biologic are likely to exist, it is a certainty that there are numerous third-party process patents with broad general applicability. Indeed, even the manufacturing equipment and its integration into the production process are subject matter that is sought to be protected. Thus, both originator and biosimilar developers face a plethora of patents directed to the production of a biopharma product.

The production of the biologic is, however, only the beginning of the process since the biologic must still be purified to a level acceptable for a human therapeutic. The purification of a biologic may involve identifying/characterising an impurity, removing impurities derived from the cellular production process and frequently impurities that may accumulate from a purification process itself. All of these aspects are potentially subject to patent protection. For example, an antibody purification may comprise three to five or more platform steps, each step of which is likely to be the subject of patent protection. The same is likely to be true for the specific impurities that may be part of the biopharma product. Patent protection frequently surrounds the analytical techniques to characterise each impurity. Therefore, a search of each purification platform step is likely to identify hundreds to thousands of patent family “hits” depending on the breadth of the search. Thus, clearing a purification process may require sorting through well over 20,000 patent families, which may be identified in a broad search.

The ultimately obtained biologic must then be characterised. Again, the complexity of the product is reflected in the complexity of the patent landscape here. A biologic may have multiple different forms (for example charged forms, modified amino acids, and/or glycosylated forms) as a result of the cell-based production and/or purification steps. Each such modification is potentially subject to scrutiny by regulatory authorities and consequently each such modification is potentially the subject of patent protection directed at, for example, controlling the incidence of each of such modified forms, removing a modified form, as well as analytical techniques to quantitate each of the modified forms. Again, depending on the modification and the breadth of a search, hundreds to thousands of addition patent families may be identified. For example, each search of “humanisation” or “glycosylation” is likely to identify in the order of 10,000 patent families.

Finally, as with the formulation of a small molecule product, the formulation of a biopharma product is ripe for patenting. A biopharma originator will generally try to protect the marketed product formulation and third parties may work to surround the active biologic with a number of different “improved” formulations. Thus, while a biosimilar developer is not required to have the same formulation as the originator, developing an alternative formulation is certain to make the FTO clearance process more arduous. For example, a simple search of claim terms “antibody” and “formulation” identifies over 10,000 patent families.[9]

In view of this crowded and complex patent landscape, it seems obvious that the path to market for a biosimilar requires a significant investment on reviewing and considering the patent rights alone; an investment that is most wisely made early in the product development. The biopharma originator is, not, however, free of this burden as the general applicability of function-based biologic claims and the wide range of processes and formulations that are the subject of patent protection means that they too will have to carefully consider their development and equally assess the patent landscape.

What can we expect in biosimilars disputes in Australia

The first pathway supporting the approval of biosimilars was introduced in Europe in 2005, followed closely by Japan and Australia in 2008, Canada in 2009, the United States of America (“US”)  in 2010 and India in 2011. Given the recency of the pathway, and given the typical development timeline for a biopharma product is approximately eight to ten years (as compared to three to five years for a small molecule),[10] it is no surprise that there are limited biosimilars approved in key regions to date. In Australia 32 biosimilars have been approved to date, as set out in Table 1 below.

Table 1: Approved biosimilars in Australia

To date, there have only been a handful of biosimilars disputes in Australia, and none of these have proceeded to substantive decision. The cases are well known to those following the development of patent law in relation to biopharma products in Australia. Two disputes to date have settled before trial: litigation between F. Hoffman-La Roche and Sandoz concerning rituximab (sold by Roche in Australia as Mabthera®),[11] and litigation between Hospira and Amgen relating to pegfilgrastim (Amgen’s product Neulasta®).[12] The third biosimilars dispute commenced to date in Australia is between Pfizer and Samsung Bioepis relating to Pfizer’s drug etanercept (Enbrel®) is ongoing but has not been heard on the merits.[13] Because of the lack of jurisprudence in Australia, there is almost no guidance from the courts on how the difference between small molecules and large will impact patent litigation in Australia.  We provide here our expectations on what biosimilars patent disputes will look like in Australia, which are informed by our experience in working on biosimilars since before the industry formed.

First, the dense biopharma patent landscape will mean that patent disputes for large molecules will involve many more patents that those for small molecules. In the US, the limited disputes between originators and biosimilar companies to date under the Biologics Price Competition Innovation Act 2009 (“BPCIA”) have demonstrated the potential impact of the density of the patent landscape. In an August 2016 complaint against Amgen, AbbVie alleged infringement of 61 patents related to its blockbuster product Humira®.[14] In the following year, AbbVie filed a similar complaint against Boehringer Ingelheim, alleging infringement of 74 patents again relating to Humira®.[15] While in both cases the number of patents actually contested was restricted by the BCPIA to ten and eight respectively, these cases highlight the volume of infringement claims that may be brought by originator companies. As biosimilars disputes start to hit the courts in Australia, we anticipate judges may be required to adjudicate in disputes involving more than ten to twenty patents. The earlier in the patent lifecycle the litigation commences, the greater this number will be.

Secondly, based purely on development timelines alone (irrespective of data exclusivity), it is logical that biosimilars will enter the market later in the patent lifecycle than small molecules. This means that the disputes for large molecules will commonly relate to patents in the later end of the patent lifecycle than small molecules. Bearing in mind the typical pattern of consecutive patenting set out above (first API, followed by formulation, process, MOT, second medical uses, alternative molecular forms), small molecule disputes may often centre around formulation patents, whereas large molecule disputes will be more likely to be focussed on process and MOT patents. In our view, biopharma disputes in Australia are likely to resolve some of the ripe issues relating to infringement of MOT patents (in particular with a “skinny label” or carve out of the patented indication), pursuant to our contributory infringement provision, section 117 of the Patents Act 1990 (Cth). This approach is consistent with the Pharmaceutical Patents Review Report published in 2013, where the authors propose an amendment to the contributory infringement provision in order to provide for (inter alia) “skinny labelling”:

Section 117 of the Patents Act should be amended to provide that the supply of a pharmaceutical product subject to a patent which is used for a non-patented indication will not amount to infringement where reasonable steps have been taken to ensure that the product will only be used in a non-infringing manner. It may be presumed that “reasonable steps” have been taken where the product has been labelled with indications which do not include any infringing indications.[16]

Thirdly, for patent litigators, possibly the most marked contrast between biologic and small molecule patents arises from the differences in the current market dynamics for large and small molecules. We discuss below some of the flow-on effects of the operation of the market dynamics for small molecules and biologics on claims for patent damages, in particular in the context of interim injunctive relief.

Differing market dynamics between generics and biosimilars

Patent focussed lawyers and attorneys will be familiar with the impact of the launch of generic small molecules (“generic”) and biosimilar products in Australia. For both large and small molecule medicines, changes in product prices are largely regulated by the National Health Act 1953 (Cth) Div. 3A,[17] the most critical of which is the mandatory 25 percent price drop triggered by the entry of a generic/biosimilar product into the therapeutic class.[18] After this, a further 5 percent price drop occurs after the product has been listed for five years.[19] Additionally, statutory price disclosures force all competitors to follow with price reductions. Originator companies may still charge more than their generic/biosimilar competitors, with the patient paying a brand premium, however, competition drives the price of the originator product down through (generally) duopoly and (subsequently) oligopoly market dynamics.

The differences between small molecule and large molecule market dynamics stem from the following:

• the higher cost of goods for biosimilars (driven by higher development costs) means that biosimilar competitors have less margin to play with when competing on price; and

• reduced number of competitors for large molecules as the considerable development cost as a “barrier to entry” for all but the very highly resourced companies.

Because generic companies are able to adopt a business model which does not require a clinical program, the lower research and development cost (perhaps combined with more efficient processes) means that generics compete heavily on price.

For the company that is the first generic to enter the market, its “first mover advantage” is pronounced. Because the generic market is highly competitive it is rare in Australia for the first generic to have more than a few months in a duopoly. Typically, within the first six months after generic entry, the vast majority of the Australian market shifts away from originator product to the generic, providing the “first mover” or “early movers” clear advantages. Generic developers that get in first (or quickly thereafter) are able to “ride the wave” of dwindling price premium as the market quickly transitions from monopoly to duopoly and then oligopoly. Typically, product price quickly crashes to just above the generic’s cost of goods, typically within a year of first generic entry. The subsequent entry of additional generics results in additional competition between generics, further eroding the market share of the originator product and the market price. Information from generic market dynamics in the US may be helpful here – typically in the US, after numerous generics have entered the market, medicine prices are reduced by as much as 85 to 95 percent.[20] In our experience, a comparable competitive effect is seen typically within six to  twelve months of generic market entry with multiple competitors (which is the norm).

However, this is not the case (yet) for large molecules. The development for a biologic is orders of magnitude greater than a small molecule. The greatest contributor to this cost is the cost of phase III clinical trials necessary for the approval of a biosimilar product but not for a generic. Further, the work required to obtain an appropriate cell line to produce the target biologic and process optimisation to maximise production in a living system is not easily comparable to the work required to design and optimise a traditional small molecule synthetic process. Development costs for biosimilars may reach up to US$100–200 million, dwarfing the development costs for a small molecule which varies between US$1–5 million for a typical small molecule.[21]

To date, we have not yet seen anything like the numbers of competitors for biologics which we have observed with small molecules. This is largely due to cost of entry of biosimilars driven by the cost of phase III clinical trials currently required to support the regulatory approval of biosimilars. This cost acts as a barrier to entry for all but the largest and most resourced companies, and results in a current market dynamic for biosimilars which differs considerably from that of small molecules.

Beyond the effect of the mandatory 25 percent price drop triggered by the Pharmaceutical Benefits Scheme (“PBS”) listing of a biosimilar product, the entry of biosimilar on the Australian market has a much more retarded effect on price. The cost of goods sold (“COGS”) for biosimilars are relatively high, leaving biosimilar companies less room to compete on price. As a result, (and based on data from the European experience) we can predict that launch prices for biosimilars are between 10 and 30 percent below the price of the originator molecule, and the competitive “race to the bottom” that we see for small molecules does not yet exist in Australia for large molecules.[22]

In Australia (as elsewhere) unlike market dynamics following generic market entry, for biosimilars we see a very slow decrease in market price, and a very gradual market penetration of biosimilars. In Australia, the impact of the launch of two recent “A-flagged” biosimilars,[23] demonstrates that less than 10 percent of the market shifted away from the originator molecule in the first two years following biosimilar launch:

• Infliximab (Remicade®, Janssen): in December 2015, Pfizer’s A-flagged biosimilar Inflectra® was PBS listed, followed in August 2017 by the listing of MSD’s A-flagged biosimilar Renflexis®.[24] By the end of 2018, three years after the first listing of a biosimilar in competition with Remicade, scripts for the two biosimilars represented only 11.7 percent of the market.[25]

• Etanercept (Enbrel®, Pfizer): in April 2017, MSD’s A-flagged biosimilar Brenzys® was PBS listed. By end 2018, Brenzys was 7.5 percent of “subsequent continuing” treatment.[26]

Resulting from this gradual decrease in market price, and gradual market penetration for biosimilars, the prize of “first mover advantage” for biosimilar products is less important than it is for generics. Atterbery et al. recently made the following observations relating to the US and European markets, which is comparable to the Australian experience:

Long-term projections of the price reductions and savings biosimilars will generate are not favorable: for the subset of biologics ultimately facing biosimilar competition, prices may decline on average by 20 to 30 percent, and US ten-year projected savings (2017-2026) total only $54 billion. In Europe, over a longer experience beginning in 2006, there are many products that still have no biosimilar competition.  Among those that do, price declines have averaged around 30 percent, a savings that evolves on average at 3.5 percent per year following biosimilar entry.[27]

To date it appears that there has been some reluctance on the part of physicians to switching from an originator biopharma product to a biosimilar. The reasons for this may be a lack of information about the biosimilars’ quality, safety and efficacy, as well as the key question for physicians of whether the biosimilar is truly substitutable or interchangeable for the biopharma product in relation to the particular disease state in question, notwithstanding what the regulatory bodies may have determined.[28] For those of us who have been around long enough to remember the re-birth of the generics industries in the 1980s, these concerns will sound familiar. Even by 1990, reports from Europe revealed that only about 30 percent of the potential generics market were actually served by generics (the remaining 70 percent were occupied by originator drugs).[29] Like generics, we believe concerns about substitutability and interchangeability of biosimilars will recede into redundancy as physicians and patients become increasingly familiar and comfortable with biosimilars.

In turn, we also expect regulatory bodies to become increasingly comfortable with biosimilars, and as analytical tools continue to sharpen, may relax (in part or entirely) the current requirements for clinical trials for biosimilars. Once this occurs, we believe the market dynamics for biosimilars will mimic the dynamics for generics.

In the meantime, the courts must deal with very different patent landscapes and very different market dynamics in patent disputes relating to biosimilars as compared to generics. The impact of the market dynamics will be most markedly felt when considering interlocutory injunctions, and the election between damages and account of profits.

The impact of market dynamics on interim injunctions

The two key enquires made by the court in determining whether to grant an interim injunction are: whether the applicant has made out a prima facie case, and whether the balance of convenience favours the grant of the interim injunction.[30]

In relation to the prima facie case enquiry, the applicant must show a sufficient likelihood of success to justify the preservation of the status quo pending trial.[31] It is expected that the answer to this enquiry will be indifferent to whether the product in question is a generic or a biosimilar.

The question of balance of convenience however is likely to be a critical point of divergence between generic and biosimilar cases. The test is well known: the applicant must demonstrate that, if no injunction is granted, it will suffer irreparable injury for which damages will not be adequate compensation.[32]

In small molecule infringement scenarios, the patentee almost routinely argues that damages will never be an adequate remedy because of the fact that in the generic market, the vast majority of the innovator’s market share will be lost to generic competitors in the first six to twelve months after entry, and the reduction in price cannot be restored to the original price pre-generic market entry.

As is demonstrated above, this is not the case for biosimilars in Australia, where market penetration and price reduction is gradual. In this significantly different competitive dynamic, it is strongly arguable that damages will be an adequate remedy. By way of example, consider the hypothetical where litigation is commenced immediately prior to entry of a biosimilar onto the market. In this case the originator habitually seeks an interim injunction to prevent the biosimilar from coming on to the market and engaging in competition prior to resolution of the litigation. In the generic market, the originator will point to the extreme loss to profit and market share it will likely suffer prior to trial. The fact of this change almost routinely works in the originator’s favour in Australia – the harm to the originator of allowing a generic competitor onto the market is marked, and courts have traditionally been sympathetic to the argument that damages are not an adequate remedy for this type of loss. This argument is greatly deflated in the case of a biosimilar entering the market. With only a gradual decrease in price over the therapeutic class (excepting the 25 percent mandatory price drop), the biologic originator’s market share and pricing power will not suffer a change comparable to that which we see in the generic market.

We expect that a respondent would be able to forcefully argue that in the case of biosimilar competition, the court should not follow the “damages are not adequate” approach traditionally used in generics litigation as the biologic originator’s loss in profit and market share will not be so great that damages could not be an adequate remedy.

In addition, as biosimilars are only likely to enter the market once the biologic molecule itself is off patent (due to the development timelines as explained above), the patent landscape for potential infringement is likely to be dominated by method of treatment and process patents. In relation to these types of patents, we are of the view that it is more open to the biosimilar competitor to argue that if damages are payable, they should be calculated by way of a reasonable royalty.

In small molecule generic patent litigation, it is most common for the patentee to seek damages for infringement rather than opting for an account of the respondent’s profits. This is because the “race to the bottom” for generic products means that the damage to the patentee will almost always be considerably more than the generic’s profits. Because of the gradual decrease in price following biosimilar launch, and because the COGS for biosimilars is expected to be less than that for the originator, we expect there will be situations where the profits of the biosimilar company will exceed the damage to the originator, which could result in an election of account of profits over damages.

Although at interim injunction stage the patentee would still be likely to make the argument that damages are not an appropriate remedy, this might be countered with a degree of force by the biosimilar manufacturer. The argument might be put that, in fact, an account of profits would be as adequate a remedy as damages. As an account of profits is calculable, the court may be more reluctant to grant an interim injunction. While we would not expect such an argument to carry the day, if put as part of a series of submissions it may assist the overall thrust of the argument that damages would be an appropriate remedy. Of course, either way, sophisticated economic evidence (involving counterfactuals) has been and will continue to be necessary.

Conclusion

We expect that as the biopharma industries mature, and as physicians, patients, the government, and the courts get more and more comfortable with biosimilars (and their patent landscapes), the market dynamics for biosimilars will become increasingly generic-like. Until then, the courts will be forced to reconsider the approach to interlocutory injunctions in Australia in these different market dynamics. Typically, for biosimilars this will occur in disputes relating to many more patents and later in the patent life cycle than is typical for generics.

Challenges to launching biosimilars in Australia are not insurmountable. Though the patent landscapes are dense and complex, and the market dynamics differ considerably to small molecules, the commercial opportunities for the well-resourced biosimilar developer are significant. In Australia, we forecast interesting disputes relating to biosimilar products magnifying issues regarding method of treatment patents and interlocutory injunctions in the short to medium term.

Endnotes 

[1] Naomi Pearce, MIP, BSc, LLB (hons), Principal, Pearce IP. Naomi is a lawyer, patent attorney and trade mark attorney, and can be reached at <naomi.pearce@pearceIP.law>. The authors thank Emily Bristow, Paralegal for her assistance in the preparation of this article.

[4] Matej Mikulic, ‘Top 15 pharmaceutical products by sales worldwide in 2018’, Statista (Webpage, 9 August 2019) <https://www.statista.com/statistics/258022/top-10-pharmaceutical-products-by-global-sales-2011/>.

[5] Informal searching carried out on <lens.org> searching claims with the terms “anti-VEGF” and “antibody” using the “Group by Simple Families” option.

[6] Informal searching carried out on <lens.org> searching all claims the term “bevacizumab” using the “Group by Simple Families” option.

[7] Informal searching carried out on <lens.org> searching all claims the term “esomeprazole” using the “Group by Simple Families” option.

[8] Merck Sharp & Dohme Ltd v Ono Pharmaceutical Co Ltd [2016] RPC 10, [1], [3].  While Merck and the exclusive licensee of the Ono patent had each developed an antibody encompassed by the claims while the patentee (Ono) had not. The claims at issue were therapeutic use claims relating to the use of antibody defined by its function.

[9] Informal searching carried out on <lens.org> searching all claims the terms “antibody” and “formulation” using the “Group by Simple Families” option.

[10] Federal Trade Commission (US), Emerging Health Care Issues: Follow-on Biologic Drug Competition, (Federal Trade Commission Report, June 2009).

[11] F Hoffman-La Roche AG v Sandoz Pty Ltd [2018] FCA 874.

[12] Hospira, Inc & Ors v Amgen Inc (Federal Court of Australia, NSD1281/2009, commenced 11 November 2009).

[13] Pfizer Ireland Pharmaceuticals v Samsung Bioepis AU Pty Ltd [2017] FCA 285.

[14] Complaint [42], [44], Abbvie Inc v Amgen Inc, Civil No 16-cv00666 (D Del 4 Aug 2016).

[15] Complaint [57], [58], Abbvie Inc. v. Boehringer Ingelheim Int’l GmbH, Civil No 17-cv-01065 (D. Del. 2 August 2017).

[16] T. Harris, , D. Nicol,  N. Gruen,. Pharmaceutical Patents Review Report (2013) Canberra, Recommendation 7.2, page xviii.

[17] National Health Act 1953 (Cth) Div. 3A, s. 99AC.

[18] Department of Health (Cth), ‘First New Brand Price Reductions’, The Pharmaceutical Benefits Scheme (Webpage, 1 April 2020) <http://www.pbs.gov.au/info/industry/pricing/pbs-items/first-new-brand-price-reductions>.

[19] Department of Health (Cth), ‘Anniversary Price Reductions’, The Pharmaceutical Benefits Scheme (Webpage, 28 November 2018) <http://www.pbs.gov.au/pbs/industry/pricing/anniversary-price-reductions>.

[20] Preston Atteberry et al., ‘Biologics Are Natural Monopolies (Part 1): Why Biosimilars Do Not Create Effective Competition’, Health Affairs Blog (Blog Post, 15 April 2019) <https://www.healthaffairs.org/do/10.1377/hblog20190405.396631/full/>.

[21] Federal Trade Commission (US), Emerging Health Care Issues: Follow-on Biologic Drug Competition, (Federal Trade Commission Report, June 2009).

[22] Thorsten Daubenfeld et al., ‘Understanding the market dynamics of bio-similars’, (2016) 13(1) Journal of Business Chemistry  33, 36.

[23] An “a-flagged” biosimilar indicates that the sponsor of the biosimilar has submitted evidence of bioequivalence or therapeutic equivalence, or that the sponsor has justified to the TGA that it is not necessary to provide evidence of bioequivalence or therapeutic equivalence. The expectation is that an “a-flagged” biosimilar may be interchanged with the originator biologic without any differences in clinical effect. See <http://www.pbs.gov.au/info/healthpro/explanatory-notes/section2/section-2-symbols>.

[24] Department of Health (Cth), ‘Infliximab’, The Pharmaceutical Benefits Scheme (Webpage) <http://www.pbs.gov.au/medicine/item/10057H-10067W-10184B-10196P-11389K-11396T-11399Y-11400B-11412P-11423F-11424G-11432Q-11445J-11448M-11449N-11450P-11459D-11461F-11481G-11482H-11483J-11486M-11487N-11488P-11489Q-11490R-11497D-11498E-11514B-11515C-11590B-11595G-11605T-11606W-11796W-11797X-4284L-5753T-5754W-5755X-5756Y-5757B-5758C-6397Q-6448J-6496X-9612X-9613Y-9617E-9654D-9674E>.

[25] Yajun Ma, ‘Uptake drivers not performing, Pharma in Focus (online, 12 August 2019) <https://www.pharmainfocus.com.au/news.asp?newsid=15286 >.

[26] Yajun Ma, ‘Uptake drivers fail to bite’, Pharma in Focus (online, 15 February 2019) <https://www.pharmainfocus.com.au/news.asp?newsid=14509>.

[27] Preston Atteberry et al., ‘Biologics Are Natural Monopolies (Part 1): Why Biosimilars Do Not Create Effective Competition’, Health Affairs Blog (Blog Post, 15 April 2019), <https://www.healthaffairs.org/do/10.1377/hblog20190405.396631/full/>.

[28] Thorsten Daubenfeld et al., ‘Understanding the market dynamics of bio-similars’, (2016) 13(1) Journal of Business Chemistry  33, 36.

[29] Thorsten Daubenfeld et al., ‘Understanding the market dynamics of bio-similars’, (2016) 13(1) Journal of Business Chemistry  33, 36.

[30] Beecham Group Ltd v Bristol Laboratories Pty Ltd [1968] HCA 1; (1968) 118 CLR 618.

[31] Australian Broadcasting Corporation v O’Neill [2006] HCA 46; (2006) 227 CLR 57.

[32] Castlemaine Tooheys Ltd v South Australia [1986] HCA 58; (1986) 161 CLR 148 at 153.