The Australian life sciences sector is subject to regulation by both Commonwealth and state or territory legislation.
The manufacture and supply of therapeutic goods is primarily regulated by Commonwealth legislation, in particular the Therapeutic Goods Act 1989 (TG Act) and its accompanying regulations, namely the Therapeutic Goods Regulations 1990 (TG Regulations) and the Therapeutic Goods (Medical Devices) Regulations 2002 (Medical Devices Regulations). Commonwealth legislation also provides a system of pricing and reimbursement of certain pharmaceutical products, known as the Pharmaceutical Benefits Scheme (PBS), through the National Health Act 1953 (NH Act) and its associated regulations.
Also relevant are the consumer protection provisions of the Competition and Consumer Act 2010 (CCA), and the equivalent state and territory legislation, which apply to all consumer transactions. State and territory legislation may impose additional requirements, including in relation to clinical and non-clinical trials, wholesale of medicines, and possession and distribution of controlled substances.
The Therapeutic Goods Administration (TGA) is the national authority responsible for regulating medicines and medical devices. The Australian Competition and Consumer Commission (ACCC) is the national authority that administers the CCA (although the CCA also provides a private right of action for enforcement of certain consumer law provisions). The Commonwealth government's Department of Health (DOH) manages, and the Department of Human Services administers, the PBS.
II THE REGULATORY REGIME
Broadly, there are three categories of therapeutic goods under the TG Act, namely biologicals, non-biologicals and medical devices. Biological and non-biological therapeutic goods are distinguished on the basis that biologicals comprise, contain or are derived from human cells or human tissues, whereas, as the name suggests, non-biologicals do not. Medical devices are products whose principal intended action is not by pharmacological, immunological or metabolic means. The TGA has the power to specify products that do, or do not, fall into these categories; for example, recombinant products (such as recombinant antibodies) are not biologicals.2
Devices that are used to administer medicines, for example a transdermal patch containing medicine, are regulated as a medicine rather than a medical device. The TGA provides guidance on the appropriate classification of products that are on the device-medicine boundary.3
The TG Act also applies to foods, cosmetics, chemicals and general consumer products in respect of which therapeutic claims are made. For example, a moisturising preparation that contains a sunscreen agent as a secondary component and has a stated therapeutic purpose (e.g., 'helps protect skin from the damaging effects of UV radiation') is regulated as a medicine.
ii Non-clinical studies
Although the use of animals in research is separately regulated by each state and territory, all require compliance with the Australian Code for the Care and Use of Animals for Scientific Purposes (Animal Code).4 The purpose of the Animal Code is 'to promote the ethical, humane and responsible care and use of animals for scientific purposes'. In most cases, an institution must be licensed to conduct such research.
The TGA has adopted a number of the European Medicines Agency's scientific guidelines for non-clinical studies.5
iii Clinical trials
Generally, a therapeutic good must be entered in the Australian Register of Therapeutic Goods (ARTG) before it can be supplied in Australia (see Section II.v). Any product not entered in the ARTG (including any new formulation, strength, dosage form, brand, etc.) is classified as an unapproved therapeutic good (UTG) and can only be supplied in certain circumstances. One such circumstance is a clinical trial.
A clinical trial in Australia must have an Australian sponsor (whether it be an individual (e.g., medical practitioner), an organisation (e.g., hospital) or a company) and must be approved by a human research ethics committee (HREC).
An HREC must have notified its existence to the Australian Health Ethics Committee of the National Health and Medical Research Council (NHMRC) and provided assurances that it is operating within NHMRC guidelines. HRECs in Australia generally provide both an ethical and a scientific review of the proposed trial and ensure compliance with the NHMRC's National Statement on Ethical Conduct in Human Research.6
Sponsors must also ensure compliance with the relevant guidelines as to good clinical practice7 and safety monitoring and reporting,8 and ensure that the use of personal information complies with the Privacy Act 1988.
Two of the avenues for supply of UTGs for clinical trials are the Clinical Trial Exemption (CTX) Scheme and the Clinical Trial Notification (CTN) Scheme. The choice of which scheme to follow lies first with the sponsor and then with the HREC.
The CTX Scheme is an approval process. The sponsor submits an application, including proposed guidelines for use, to the TGA. The trial may not commence until written advice is received from the TGA and approval obtained from an HREC and the institution at which the trial will be conducted. Any number of clinical trials can be conducted without further assessment by the TGA, provided that the use of the product falls within the approved guidelines for use and notification is given to the TGA of each trial conducted.
The CTN Scheme is a notification scheme. All material relating to the proposed trial is submitted directly to the HREC, which is responsible for reviewing the scientific validity of the trial design, the balance of risk versus harm of the therapeutic good, and the ethical acceptability of the trial and approval of the trial protocol. The institution at which the trial will be conducted gives the final approval. The TGA does not evaluate any data relating to the trial.
Studies in which products already entered in the ARTG are used within the conditions of their marketing approval are not subject to CTN or CTX requirements but still need to be approved by an HREC.
Commercial sponsors of clinical trials are required to hold insurance of at least A$10 million or A$20 million depending on the state or territory. Additionally, members of Medicines Australia are recommended, and other sponsors encouraged, to comply with the Compensation Guidelines.9
iv Named-patient and compassionate use procedures
The TG Act provides mechanisms that allow individuals to gain limited access to UTGs (defined in Section II.iii). Any UTG can potentially be obtained via these mechanisms, with the exception of drugs of abuse where the manufacture, possession, sale or use is prohibited by law or where other customs controls apply. Generally, the Commonwealth government does not subsidise the cost of UTGs.
The Special Access Scheme (SAS) provides three pathways for access to UTGs:
- Category A is a notification pathway that can only be accessed by medical practitioners (i.e., doctors) for patients who are 'seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment'.
- Category B is an application pathway that can be accessed by health practitioners (e.g., doctors, dentists, radiographers, nurses, pharmacists and psychologists) for patients who do not fit the Category A definition and where the UTG is not deemed to have an 'established history of use'. Approval from the TGA is required before the UTG may be accessed.
- Category C is a notification pathway that allows health practitioners to supply UTGs that are deemed to have an 'established history of use' without first seeking prior approval. The TGA has published lists of goods deemed to have an 'established history of use' and the types of health practitioners who may supply those goods.10
There is no obligation to supply a UTG merely because it has been approved under the SAS, but if a supplier chooses to do so it must comply with reporting obligations to the TGA, including six-monthly reports detailing the supply of UTGs under the Scheme and communication of any information that has an important bearing on the benefit-risk assessment of the product.
Access to UTGs is also possible through an authorised prescriber, the personal importation scheme or a clinical trial. An authorised prescriber is a medical practitioner who is allowed to prescribe a specified UTG (or class of UTGs) to specific patients (or classes of recipients) with a particular medical condition. An authorised prescriber does not need to notify the TGA when they are prescribing the UTG but must report to the TGA the number of patients treated on a six-monthly basis. Under the personal importation scheme, an individual can import a UTG to be used by that individual or a member of their immediate family. Quantity restrictions and customs rules apply.
In 2018, an online system was introduced to enable electronic submission of SAS and authorised prescriber applications to the TGA.
v Pre-market clearance
A therapeutic good must be entered in the ARTG before it can be supplied in Australia, subject to certain exceptions (see Sections II.iii and II.iv). The sponsor of the good must be a resident of Australia or be an incorporated body in Australia and conducting business in Australia where the representative of the company is residing in Australia.
The route of evaluation, including time frame and fees, depends on the category of the application. The TGA's guidelines for the regulation of prescription medicines,11 biologicals12 and medical devices13 provide detailed guidance on the application processes.
Medicines are either 'registered' or 'listed'. Registration involves individual evaluation of the quality, safety and efficacy of the product and is required for higher risk medicines (including all prescription medicines). Listing typically does not require demonstration of efficacy and is reserved for lower risk medicines (including some over-the-counter medicines and most complementary medicines). See also Section IX.i.
The approval process can be expedited where the medicine has been approved by a 'comparable overseas regulator' (COR) or through the priority review pathway. To rely on a COR, the medicine must be identical (in terms of dosage form, strength, formulation and manufacture), and the indications must be identical or equivalent (to allow for minor textual differences), to the overseas approval. To be eligible for the priority review pathway, the medicine must satisfy a number of conditions: it must be indicated for the treatment, prevention or diagnosis of a life-threatening or seriously debilitating condition; there must be no other goods registered on the ARTG for that condition (or there must be substantial evidence demonstrating a significant improvement in efficacy or safety compared to those goods); and there must be substantial evidence demonstrating that the medicine provides a major therapeutic advance.
The application and evaluation fees for a new chemical entity are A$48,800 and A$195,700, respectively (or A$51,700 and A$207,000, respectively, for the priority pathway) and for a new biological are A$1,110 and A$73,700 to A$239,500, respectively.
In relation to follow-on products, to gain registration a generic medicine must demonstrate bioequivalence to the originator product and a biosimilar must demonstrate comparability (biosimilarity) to the reference biological medicine. Applications to register biosimilars are managed through the prescription medicines process and, as such, guidance is currently set out in the Australian Regulatory Guidelines for Prescription Medicines.14
Medical devices are 'included' on the ARTG, which requires compliance with the 'essential principles'15 as to quality, safety and performance, and the appropriate conformity assessment procedures. There are three slightly different application processes depending on whether the medical device is classified as being Class I (as defined in the Medical Devices Regulations), export-only or other than Class I.
Similarly to medicines, the approval process may be expedited where the medical device has been approved by a COR or through priority review designation. The application fees for new medical devices vary depending on the class of the device and the level of audit and conformity assessment required.
vi Regulatory incentives
Patent term extension
The Patents Act 1990 provides that in situations where the time taken for regulatory approval of a pharmaceutical substance claimed by the patent exceeds five years, the term of the patent may be extended. However, the period of extension cannot exceed five years. Extensions are not available for patents for medical devices.
On 25 August 2018, the Commonwealth government repealed Section 76A of the Patents Act, removing the financial reporting requirements (as to the amount spent in Australia, and Commonwealth funds spent, on research and development of the drug that is the subject of the patent) imposed upon grant of an extension.
The TG Act provides a data exclusivity period of five years in relation to therapeutic goods containing a new active component (that is, an active substance that has not previously been a component of a product entered in the ARTG). The exclusivity period applies to information provided to the TGA in relation to an application for registration, provided that the information is not available to the public and the TGA has not been given written permission to use it.
Products for rare diseases
Orphan drugs are medicines, vaccines or in vivo diagnostic agents that are intended to treat, prevent or diagnose a life-threatening or seriously debilitating condition that is rare or for which supply to do so is not likely to be financially viable. As an incentive to develop products for these small markets, the TGA waives the application and evaluation fees normally required.
vii Post-approval controls
Sponsors are typically required to have a nominated contact person responsible for fulfilling the sponsor's reporting requirements to the TGA. Under the TG Act, a sponsor must provide to the TGA, in writing, information relevant to the benefits and risks of products entered in the ARTG as soon as the sponsor becomes aware of it. This includes information that: indicates that the goods may have an unintended harmful effect or are less efficacious than reported in the original application; is contradictory to that previously provided to the TGA; and indicates that the quality, safety or efficacy of the goods is unacceptable. Failure to notify the TGA can lead to removal of the product from the ARTG as well as civil and criminal penalties. Sponsors are also required to submit regular periodic safety update reports and, from 1 January 2019, report shortages of, or decisions to permanently discontinue, reportable medicines (see Section IX.i).
The TGA also takes an active role in post-market surveillance, including random and targeted laboratory testing of approved products, GMP audits, and inspections of manufacturer's or sponsor's records. In addition, there are systems in place by which anyone can report adverse effects involving medicines, vaccines and medical devices. Adverse event reports are published online.16
The transfer of product approvals is relatively straightforward but may only take place once all the regulatory issues have been addressed.
viii Manufacturing controls
The manufacture of therapeutic goods must meet an acceptable standard of good manufacturing practice (GMP), the nature of which depends on the type of therapeutic good.
Medicines, active pharmaceutical ingredients, and biologicals that comprise or contain live animal cells, tissues or organs must meet the Guide to Good Manufacturing Practice for Medicinal Products published under the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/S Guide to GMP).17 The Australian Code of Good Manufacturing Practice for Human Blood and Blood Components, Human Tissues and Human Cellular Therapy Products applies to blood, human tissues and human cellular product manufacturers that undertake the collection, processing, testing, storage, release for supply, and quality assurance of such products.18 Australian manufacturers of medicines and biologicals are required to obtain a licence from the TGA, while overseas manufacturers may either be approved by the TGA itself or the TGA may accept certification by a comparable overseas regulator. The TGA has the right to undertake an audit of an overseas manufacturing site at any time and fees apply.
Manufacturers of medical devices need to comply with the appropriate conformity assessment procedures and may require certification by the TGA.
Transfer of ownership of manufacturing facilities is straightforward but might trigger an audit, particularly if the transferee is not an entity that has previously been audited by the TGA.
ix Advertising and promotion
All advertising of therapeutic goods must comply with the TG legislation.
Advertising to the public of certain therapeutic goods, including biologicals, prescription medicines and controlled substances, is prohibited. For those goods that can be advertised to the public, compliance with the Therapeutic Goods Advertising Code (No. 2) (2018 Code) is required (see also Section IX.i regarding the transition from the 2015 Code). The TGA is responsible for handling complaints about the advertising of therapeutic goods to the public.
All claims must be valid, accurate, and substantiated (i.e., supported by evidence), and consistent with the indications or intended purpose as entered in the ARTG.
Certain advertisements require approval by the TGA before publication. These include advertisements referring to a serious form of a disease, condition, ailment or defect, being a form for which: it is medically accepted that diagnosis, treatment or supervision by a suitable qualified health professional is required; or a diagnostic, preventative, monitoring, susceptibility or pre-disposition test requires medical interpretation or follow-up.
Advertisements must also be in accordance with the CCA, which imposes penalties on persons who engage in conduct that is (or is likely to be) misleading or deceptive, or make false representations (e.g., in relation to the quality, benefits or performance characteristics of goods).
Advertising and promotion of therapeutic goods is also subject to codes of conduct maintained by the relevant industry bodies. The four main codes are:19 the Medicines Australia Code of Conduct (MA Code), covering the discovery-driven pharmaceutical industry; the Generic and Biosimilar Medicines Association Code of Practice, covering generic and biosimilar suppliers; the Medical Technology Industry Code of Practice, covering the medical devices sector; and the Australian Self Medication Industry Code of Practice, covering the non-prescription consumer healthcare sector.
Membership of each of the sponsoring bodies, and hence applicability of the relevant code, is effectively voluntary but regulatory conditions may mandate code compliance. For example, it is typically a condition of registration of prescription medicines that any promotion complies with the requirements of the MA Code, regardless of whether the sponsor is a member of Medicines Australia.
x Distributors and wholesalers
Distributors and wholesalers are regulated at a state and territory level. Typically, a licence or permit is required to wholesale medicines and controlled drugs listed in the Poisons Standard (see Section II.xi) and compliance with the PIC/S Guide to GMP and the Australian Code of Good Wholesaling Practice for Medicines in Schedules 2, 3, 4 and 8 is mandated.20
xi Classification of products
Australia has a national scheduling system for the categorisation of medicines, the Poisons Standard,21 which is adopted by each state and territory as part of its poisons and controlled substances legislation. Products are divided into 10 schedules, the most relevant for human applications being:
- Schedule 2 – pharmacy medicines;
- Schedule 3 – pharmacy-only medicines;
- Schedule 4 – prescription-only medicines;
- Schedule 8 – controlled drugs; and
- Schedule 9 – prohibited substances.
The scheduling of a product determines the level of regulatory control, in particular in relation to availability and advertising restrictions. Scheduling decisions are made by the secretary to the DOH or a delegate.
Medical devices are classified in accordance with the Medical Devices Regulations. In vitro diagnostic (IVD) medical devices are classified separately from other medical devices. Criteria for classification include degree of invasiveness, intended length of use, and whether it contains a medicine or matter of animal origin (for non-IVD devices) or the intended purpose of the device in accordance with the degree of personal and public health risk (for IVD devices).
xii Imports and exports
Therapeutic goods typically must be entered in the ARTG to be imported into or exported from Australia. The import or export of goods not entered in the ARTG, such as for use in clinical trials, requires approval from the TGA unless an exemption applies (see Section II.iv). See also Section II.xiii.
xiii Controlled substances
Australia is a signatory to the Single Convention on Narcotic Drugs 1961. Commonwealth legislation embodies the obligations of this convention through the Narcotic Drugs Act 1967 (Drugs Act) and requires licences and permits to manufacture, import and export certain narcotic drugs, psychotropic substances, precursor chemicals, antibiotics and androgenic or anabolic substances. The possession, use and sale of controlled substances (and relevant licences) are also regulated at a state and territory level.
The Drugs Act was amended in 2016 to permit the cultivation and supply of cannabis for medicinal and related scientific purposes and again in 2018 to permit export of Australian manufactured medicinal cannabis products. Licences are granted by the Office of Drug Control, which is part of the DOH. The DOH, together with state and territory governments, has developed new clinical guidance documents for prescribers of medicinal cannabis for treating chemotherapy-induced nausea and vomiting, epilepsy, multiple sclerosis, chronic non-cancer pain and palliative care.22 Access is provided under the SAS or through an authorised prescriber (see Section II.iv).
The TGA is primarily responsible for enforcement actions and has the power to suspend or cancel non-compliant goods from the ARTG, issue infringement notices, accept court-enforceable undertakings, and commence civil and criminal actions. The degree of the TGA's response is dependent on whether non-compliance is accidental, opportunistic or intentional. The TGA supports voluntary compliance and, in practice, a number of issues are resolved by the relevant industry body and code, such as in relation to the marketing and promotion of products.
In addition, the ACCC has powers in relation to misleading and deceptive conduct, product recall obligations, and consumer rights and remedies (see also Sections VII and VIII).
III PRICING AND REIMBURSEMENT
Under the PBS, the Commonwealth government subsidises the cost of certain prescription medicines. While manufacturers have a choice as to whether they supply their products under the PBS, it is generally accepted that PBS listing is a prerequisite to the commercial success of medicines.
Applications for listing of new medicines on the PBS are made to the Pharmaceutical Benefits Advisory Committee (PBAC), which in turn makes a recommendation to the Minister for Health. Under the NH Act, the PBAC must consider the effectiveness and cost of the proposed medicine compared with alternative therapies (comparators). The PBAC cannot make a positive recommendation for a medicine that is substantially more costly than a comparator unless it is satisfied that the proposed medicine also provides a significant improvement in health. Claims of cost-effectiveness must be supported by appropriate economic models.
In recent years, there has been a significant policy emphasis on managing and minimising the cost to government of the PBS. To manage the overall cost of a new medicine, the government may require a sponsor to enter into a cost-sharing agreement. This arrangement may take the form of a rebate, for example, whereby the sponsor rebates a percentage of government expenditure for sales in excess of a set dollar value.23
Products listed on the F1 formulary (which contains single-branded medicines that are deemed not interchangeable at the patient level with another medicine that has multiple PBS-listed brands) are subject to automatic one-off price reductions on the fifth, 10th and 15th anniversaries of the PBS listing date of 5, 10 and 5 per cent, respectively. These reductions take effect on 1 April each year (up to 2022 for the fifth anniversary reduction and 2021 for the 10th and 15th anniversary reductions).
In relation to follow-on products, applications for the listing of biosimilars will be considered by the PBAC whereas applications for the listing of generic medicines will usually be considered by a delegate of the DOH.
Applications for the listing of biosimilars must be supported by a clinical evaluation, with an estimate of the expected use of the product and its consequent impact on government expenditure. Applications for the listing of generic medicines must include a statement from the TGA regarding the equivalence of the new brand to currently listed brands. In some instances, the new brand may not have TGA approval for all indications of the currently listed brands and will only be listed for its approved indications.
The listing of the first generic or biosimilar version of a product on the PBS results in a statutory reduction in the price of the listed brand. On 1 October 2018, the minimum reduction was increased from 16 to 25 per cent.24 If, however, the listed brand has experienced price reductions since 1 January 2016 (or, if it was listed on a later date, since that date) of: 40 per cent or more, no statutory reduction will apply; or between 15 and 40 per cent, the new price of the listed brand must not exceed 60 per cent of the price as at 1 January 2016 (or, if it was listed on a later date, as at that date). In addition, the Minister may now exercise his discretion not to apply the statutory price reduction in whole or part.
Following this, the PBS price disclosure regime requires sponsors of all brands of the drug to provide data to the DOH concerning sales revenue, volume of sales, and discounts or other incentives offered by sponsors, such as cash rebates. This information is then used to adjust the subsidy that the government pays to more closely reflect the price at which the medicines are supplied in the market.
There is no formal scheme specifically for reimbursement for medical devices. However, under Medicare, a wide variety of medical procedures are reimbursed by the government, including diagnostic tests, thus providing a de facto reimbursement scheme for the use of those devices.
IV ADMINISTRATIVE AND JUDICIAL REMEDIES
i Challenging a decision under the Therapeutic Goods Act 1989
A person wishing to challenge a decision made under the TG legislation may: request an internal review by the TGA; apply to the Administrative Appeals Tribunal (AAT) pursuant to the Administrative Appeals Tribunal Act 1975; or apply to the Federal Court of Australia (FCA) pursuant to the Administrative Decisions (Judicial Review) Act 1977.
A request for an internal review will lead to a reconsideration of the merits of the 'initial decision' by the Minister of Health. An initial decision includes decisions relating to the registration and listing of therapeutic goods on the ARTG, suspension and cancellation of medical devices from the ARTG, and revocation or suspension of a manufacturing licence. Following such a request, the Minister must reconsider the initial decision and may confirm or revoke the initial decision, or revoke the initial decision and make a decision in substitution.
An application to the AAT can also involve a reconsideration of the merits of the decision (including discretionary matters) and may also, in certain circumstances, take into account new information not available when the initial decision was made.
A review by the FCA will be limited to correcting an error of law, including on the grounds that: the decision was an improper exercise of power or was unreasonable; the decision-maker took into account irrelevant factors or failed to take into account relevant factors; and there was a denial of natural justice.
ii Challenging a decision by the PBAC
An applicant whose submission to the PBAC has not resulted in a recommendation to list, or to extend the listing of, a drug on the PBS is entitled to apply to have the decision reviewed by the FCA. However, in circumstances where new information or evidence is likely to be relevant, the DOH encourages applicants to resubmit the drug for consideration by the PBAC, as such material will not be considered in judicial review.
V ACTIVE INGREDIENT PRESCRIBING
The government announced in its 2018–2019 Budget plans to implement electronic prescribing from late 2019. This included an initiative for active ingredient prescribing (AIP), which was aimed at increasing patient understanding of the active ingredients in their medicines, and at increasing the uptake of generic and biosimilar medicines.
The AIP initiative was implemented in the National Health (Pharmaceutical Benefits) Regulations Amendment (Active Ingredient Prescribing) Regulations 2019 (the Amending Regulations) and came into effect on 31 October 2019. This required all prescribers issuing electronic PBS scripts to identify medicines by the active ingredient rather than by brand name, which had been the preferred practice. Further, the prescribing software must not default to include brand names on prescriptions. The exceptions to this include the following:
- where the prescriber issues handwritten scripts;
- paper-based medication charts in residential aged care facilities;
- medicines that have four or more active ingredients;
- where it is deemed clinically necessary by the prescriber, the brand name can be included on a prescription provided it is included after the active ingredient; and
- other exceptions deemed necessary by the DOH for practicality and safety reasons.
A 12-month transition period has implemented to allow prescribers sufficient time to update prescribing software to meet the new AIP requirements.
VI FINANCIAL RELATIONSHIPS WITH PRESCRIBERS AND PAYORS
The financial relationships between pharmaceutical or device companies and prescribers are largely regulated by industry codes. The scope and detail of the restrictions imposed differs depending on the relevant membership (see Section II.ix).
The MA Code requires that members report on payments or benefits provided to individual healthcare professionals, including fees paid for:
- speaking at an education meeting or event;
- sponsorship to attend an educational event;
- the purpose of market research where the identity of the healthcare professional is known to the pharmaceutical company that contracted the market research; and
- being an Advisory Board member.
Pharmaceutical companies must not make a transfer of value to a healthcare professional unless they have taken appropriate steps to give notice of this disclosure obligation. However, this does not include payments in relation to research and development work, including clinical trials.
There is no specific legislation dealing with relationships with payers but there are various provisions at both the Commonwealth and state or territory levels relating to bribery and facilitation payments. For example, under Commonwealth legislation, it is an offence to dishonestly provide or offer (directly or indirectly) a benefit with the intention of influencing a Commonwealth public official (such as from the TGA or the PBAC) in the exercise of their duties, or where the receipt of the benefit would tend to influence the exercise of those duties.
VII SPECIAL LIABILITY OR COMPENSATION SYSTEMS
There are no specific liability or compensation systems designed to compensate persons injured by medicines or medical devices in Australia. Instead, product liability claims are made under common law (such as the tort of negligence or breach of contract) or state, territory or Commonwealth legislation (such as the CCA). The CCA provides that manufacturers are liable directly to consumers for goods that: do not correspond with their description; are not of acceptable quality; are unfit for their stated purpose; do not comply with a safety standard; or do not comply with express warranties.
As noted above, commercial sponsors of clinical trials are required to hold insurance of at least A$10 million or A$20 million, depending on the state or territory, and are encouraged to comply with Medicines Australia's Compensation Guidelines. In relation to public sector clinical trials, an indemnity or insurance cover for the trial site and investigator is provided by the state or territory.
VIII TRANSACTIONAL AND COMPETITION ISSUES
i Competition law
The ACCC is responsible for enforcing Australia's competition and restrictive trade practices laws, provided for primarily in the CCA (defined in Section I). Although the ACCC has successfully taken action against pharmaceutical companies for breaches of consumer law (e.g., for misleading and deceptive conduct), it has rarely pursued pharmaceutical companies for restrictive trade practices. In addition to the imposition of fines by the ACCC (which can be in the range of millions of dollars), there is the potential for class actions.
In 2014, the ACCC instituted proceedings for misuse of market power against a pharmaceutical company for the first time. The conduct in question was that company's supply, directly to community pharmacies, of a generic version of its product shortly before expiry of the relevant patent and a scheme whereby those pharmacies would be paid rebates based on how much product (originator and generic brands) was purchased. In 2018, the Full Court of the FCA found that the company had taken advantage of its substantial market power but did not accept that it had acted for the purpose of substantially lessening, or deterring or preventing, competitive conduct. The ACCC's application for special leave to appeal to the High Court was dismissed in October 2018, ending the action. Section 46 of CCA has now been amended to encompass conduct that has the effect or likely effect of substantially lessening competition.
ii Transactional issues
Market authorisations are transferable pursuant to the TG Regulations. The secretary of the DOH must be notified in writing within three months of the transfer and may request further information before amending the ARTG.
If there is to be a change in the manufacturing site, this may take some time to process. This is an important consideration if the medicine is listed on the PBS where a condition of PBS listing is an obligation to ensure continuity of supply.
IX CURRENT DEVELOPMENTS
i Medicine and medical device regulatory reforms
Australia's regulatory framework for therapeutic goods is continuing to undergo reform in response to the Review of Medicines and Medical Devices Regulation. A number of key developments that were completed in 2018 are discussed below. Moving forward, the TGA plans to: designate conformity assessment bodies in Australia to undertake medical device conformity assessment certification; remove advertising pre-approvals to transition public advertisements of medicines to a more self-regulated model; enhance post-market monitoring of complementary medicines and medical devices; align the medical device regulations more fully with the European Union framework; and develop new processes for better use of evaluation reports from comparable overseas regulators.
Advertising of therapeutic goods
On 1 January 2019, the 2018 Code replaced the 2015 Code (defined in Section II.ix). The 2018 Code was developed following extensive consultation with stakeholders and is said to provide advertisers with clarity in relation to:
- definitions of terms (including 'health warning' and 'prominently displayed or communicated');
- the requirements for scientific or clinical claims and consistency with public health campaigns; and
- certain requirements relating to endorsements and testimonials.
The TGA has stated that, as part of the transition to the 2018 Code, it will take a pragmatic approach to its compliance activity during 2019, focusing on the risk posed to public health and safety. Thus, where an advertisement is not compliant with the 2018 Code but would have been compliant with the 2015 Code, in particular in relation to requirements such as mandatory statements, scientific citations and testimonial disclosures, it is unlikely that the TGA will consider such non-compliance to pose a significant risk to public health. Accordingly, complaints of this type received during the first half of the year will unlikely attract more serious action than a reminder of the obligations under the 2018 Code, whereas complaints received during the second half of the year will require information such as the process being applied to correct the advertising along with associated dates before the TGA will determine whether to apply enforcement discretion.
The 2018 Code was amended by the Therapeutic Goods Amendment (Therapeutic Goods Advertising Code) Instrument 201925 on 30 July 2019 in response to feedback from industry and the Therapeutic Goods Advertising Consultative Committee. The amendments to the 2018 Code include:26
- correcting a small number of errors;
- clarifying the status of advertising statements for therapeutic goods in relation to pregnancy;
- ensuring that advertisers who are authorised to include information in their promotional materials highlighting that efficacy of their medicine has been assessed by the TGA can do so without breaching the 2018 Code; and
- a number of changes that provide more flexibility to advertisers in how they include mandatory information in their advertisements.
Relatedly, the Therapeutic Goods Amendment (2017 Measures No. 1) Act 2018 introduced new and enhanced penalties for advertising offences, including a three-tiered structure to the general advertising offences under Section 42DL of the TG Act comprising:
- a strict liability offence, which attracts a maximum penalty of A$21,000;
- an ordinary offence, which attracts a maximum penalty of A$210,000 or 12 months' imprisonment, or both; and
- a high-level offence (whereby use of the goods in reliance on the advertisement (1) has resulted in, will result in, or is likely to result in, harm or injury to any person, or (2) if so used would result in, or would be likely to result in, harm or injury to any person), which attracts a maximum penalty of A$840,000 or five years' imprisonment, or both.
The amending act also introduced continuing offences, whereby a person commits a separate offence for each day during which the contravention continues, with a maximum daily penalty of 10 per cent of the maximum pecuniary penalty that can be imposed in respect of that offence.
New approval pathways
The TGA has implemented a provisional approval pathway for prescription medicines whereby sponsors may apply for time-limited provisional registration on the ARTG (up to a maximum of six years). The eligibility criteria for provisional approval requires the registration to:27
- be a new prescription medicine or a new indication of an already registered prescription medicine;
- provide a favourable comparison against existing therapeutic goods;
- provide a major therapeutic advance; and
- include evidence of a plan to submit comprehensive clinical data.
The medicine or use must be for the treatment, prevention or diagnosis of a life threatening or seriously debilitating condition and be likely to provide a major therapeutic advance, and there must be evidence of a plan to submit comprehensive clinical data. The pathway is intended to provide access to promising new medicines where the TGA assesses that the benefit of early availability of the medicine outweighs the risk inherent in the fact that additional data are still required. On 17 July 2019, Pembrolizumab (KEYTRUDA) became the first medicine to have additional indications approved by the TGA via the provisional approval pathway.
The listed medicines regime has also been reformed with the introduction of 'permitted indications' and the 'assessed listed medicines pathway'.
All medicines listed under Section 26A of the TG Act are now required to contain only indications that the TGA has determined to be 'permitted indications'.28 The intention is to provide transparency as to the indications suitable for listed medicines so as to reduce sponsor non-compliance and improve protection for consumers from misleading and inappropriate claims.
Sponsors wishing to list a medicine with an indication other than a permitted indication may either apply for new indications to be added to the list of permitted indications or utilise the assisted listed medicines pathway. The new pathway sits between the current listed (lower risk) and registered (higher risk) pathways and permits access to 'intermediate indications', such as references to:
- the prevention, alleviation, or cure of a non-serious disease, ailment, defect or injury (e.g., alleviates mild dermatitis); or
- a serious form of disease (e.g., relieves rheumatoid arthritis symptoms, such as inflammation and pain).
Under the assessed listed medicines pathway, the sponsor self-certifies the safety and quality of the product and the TGA conducts pre-market assessment of efficacy evidence supporting the proposed indications.
Sponsors of existing listed medicines must ensure that their products comply with the new regime before 6 March 2021.
Reporting medicine shortages
From 1 January 2019, it became mandatory for sponsors to report to the TGA shortages of, and decisions to discontinue, 'reportable medicines' (i.e., prescription medicines, controlled drugs and other medicines determined by the Minister).
A medicine is in 'shortage' if its supply in Australia will not, or will not likely, meet the demand for it at any time in the next six months for all the patients in Australia who take, or may need to take, the medicine. Shortages will be determined at a national level, with instances of short supply or unavailability at particular locations or from particular suppliers not requiring reporting.
The scheme imposes particular time limits, with sponsors required to report:
- a shortage of 'critical impact' as soon as possible (but no later than two working days after the sponsor knows, or ought reasonably to have known, of the shortage) and any other shortage within 10 working days; and
- a decision to discontinue of 'critical impact' at least 12 months before the discontinuation is proposed to occur (or, if this is not possible, as soon as practicable after the decision is made) and any other discontinuation at least six months beforehand (or as soon as practicable).
A shortage or discontinuation is deemed to have 'critical impact' if:
- there are no registered goods that could reasonably be used as a substitute (or a substitute good exists but is not likely to be available in sufficient quantities to meet demand), and the shortage or discontinuation will have the potential to have a life-threatening impact on, or a serious impact on the physical or mental health or functioning of, patients who take, or may need to take, the medicine; or
- the medicine is on the Medicines Watch List.
Failure to notify the TGA may result in a civil penalty of up to A$21,000 for an individual and A$210,000 for a body corporate.
ii Competition law
On 20 September 2018, the Commonwealth government introduced to Parliament the Treasury Laws Amendment (2018 Measures No. 5) Bill 2018. The Bill seeks to repeal Section 51(3) of the CCA, which exempts conditional licensing or assignments involving intellectual property from a number of competition law prohibitions. The proposed amendment is said to bring Australia into alignment with other comparable jurisdictions, including Canada, Europe and the United States.
If passed, any such arrangements, whether existing or new, will need to comply with the restrictive trade practices provisions of the CCA, although intellectual property owners will be afforded six months to review their existing arrangements.
The Bill was passed on 18 February 2019, and on 13 September 2019, the repeal of Section 51(3) of the CCA came into effect. Prior to the repeal, the ACCC had published guidelines to facilitate the transitional process. The guidelines set out the approach the ACCC would take following the repeal, including its understanding and interpretation of the law following the repeal.
Conduct involving intellectual property rights, previously the subject of exemptions, is now subject to the anticompetitive conduct prohibitions of the CCA. The ACCC guidelines summarise the main prohibitions as follows:29
- cartel conduct (Division 1 of Part IV of the CCA);
- making or giving effect to a contract, arrangement or understanding, or engaging in a concerted practice for the purpose, or with the effect or likely effect, of substantially lessening competition (Section 45 will of the CCA); and
- engaging in exclusive dealing with a purpose, the effect or likely effect of substantially lessening competition (Section 47 of the CCA).
From 13 September 2019, conduct occurring before, on or after commencement in respect of granting a licence, making an assignment or entering into a contract, arrangement or understanding became subject to the prohibitions.
Corporations found by a court to have contravened the anticompetitive conduct prohibitions are subject to penalties for each act or omission (Section 76(1A)(b) of the CCA):
- A$10 million;
- if the court can determine that the benefit obtained by the corporation was a direct or indirect result of the contravening conduct – three times the value of the benefit; or
- if the court cannot determine the value of benefit obtained – 10 per cent of the annual turnover of the corporation during the 12-month period following the contravening conduct.
For individuals, a court may impose a maximum pecuniary penalty of A$500,000 for each contravention of an anticompetitive conduct prohibition.
1 Anthony Muratore is of counsel and Jenny Wong is an associate at Jones Day. Stephen Rohl was a co-author of this chapter with Anthony Muratore in previous editions, including the seventh edition of The Life Sciences Law Review.
2 See, for example, for medical devices: Therapeutic Goods (Articles that are Medical Devices) Specification 2014 and Therapeutic Goods (Articles that are not Medical Devices) Order No. 1 of 2017; and for biologicals: Therapeutic Goods (Things that are Biologicals) Specification 2019, Therapeutic Goods (Things that are not Biologicals) Determination No. 1 of 2011 and Therapeutic Goods (Excluded Goods) Determination 2018.
7 For medicines and biologicals: Guideline for Good Clinical Practice ICH E6(R2) annotated with TGA comments (www.tga.gov.au/publication/note-guidance-good-clinical-practice); and for medical devices: ISO 14155:2011 Clinical Investigation of Medical Devices for Human Subjects – Good Clinical Practice (www.iso.org/standard/45557.html).
8 Safety Monitoring and Reporting in Clinical Trials Involving Therapeutic Goods: https://www.nhmrc.gov.au/about-us/publications/safety-monitoring-and-reporting-clinical-trials-involving-therapeutic-goods.
10 Medicines: Therapeutic Goods (Authorised Supply of Medicines) Rules 2019; biologicals: Therapeutic Goods (Authorised Supply of Specified Biologicals) Rules April 2018; and medical devices: Therapeutic Goods (Authorised Supply of Specified Medical Devices) Rules March 2018.
15 There are six general essential principles that apply to all medical devices and a further nine essential principles regarding design and construction that apply to medical devices on a case-by-case basis. These are set out in Parts 1 and 2, respectively, of Schedule 1 of the Medical Devices Regulations.
17 Excluding Annexes 4, 5 and 15: https://www.tga.gov.au/publication/pe009-13-pics-guide-gmp-medicinal-products.
19 https://medicinesaustralia.com.au/wp-content/uploads/sites/52/2010/01/20150617-PUB-Code- Edition-18-FINAL.pdf; https://www.gbma.com.au/wp-content/uploads/2013/01/GBMA_Code_4thEdition_Final_160202.pdf; https://crm.mtaa.org.au/sites/default/files/uploaded-content/field_f_content_file/code_of_practice_e11_-_2020.pdf; https://www.chpaustralia.com.au/Tenant/C0000022/Documents/CHP%20Australia/ASMI%20Code%20of%20Practice%20Nov%202016.pdf.
23 For further information, see the Guidelines for Deeds of Agreement for the Pharmaceutical Benefits Scheme: www.pbs.gov.au/info/industry/listing/elements/deeds-agreement.
24 This increase in the statutory price reduction will revert to 16% from 1 July 2022.
28 The current list of permitted indications is set out in the Therapeutic Goods (Permissible Indications) Determination (No. 2) 2019: https://www.legislation.gov.au/Details/F2019L01455.