2019-2020

THE PARLIAMENT OF THE COMMONWEALTH OF AUSTRALIA

HOUSE OF REPRESENTATIVES

THERAPEUTIC GOODS AMENDMENT (2020 MEASURES NO. 2) BILL 2020

EXPLANATORY MEMORANDUM

(Circulated by authority of the Minister for Health, the Hon Greg Hunt MP)

THERAPEUTIC GOODS AMENDMENT (2020 MEASURES NO. 2) BILL 2020 OUTLINE

The Therapeutic Goods Amendment (2020 Measures No. 2) Bill 2020 (the Bill) makes a number of amendments to the Therapeutic Goods Act 1989 (the Act).

These amendments:

a)                 improve the availability of prescription medicines during medicine shortages by allowing pharmacists (within safety parameters) to substitute a different medicine for one that has been prescribed for a person in Australia, where there is a serious scarcity of the prescribed medicine;

b)                allow the making of regulations to establish a unique device identification database and related requirements for the improved traceability and monitoring of medical devices in Australia;

c)                 enable APS employees in the Department of Health to obtain, possess or convey goods for the purposes of identifying if the Act or regulations have been complied with, without contravening a law of (in particular) a State, the Australian Capital Territory or the Northern Territory;

d)                allow the making of regulations to prohibit the import, export, supply or manufacture of therapeutic goods that are prohibited under international agreements that Australia has ratified (in practice, in relation to the prohibition or restriction of substances that are associated with particular safety concerns);

e)                 remove a potential impediment to the timely availability of COVID-19 vaccines in Australia by enabling the Secretary to consent to the importation and supply of registered or listed therapeutic goods (which would, in relation to registration, include any COVID-19 vaccines that are given marketing approval) that do not have their registration or listing number on the label;

f)                  improve the flexibility of the data protection scheme for assessed listed medicines to further encourage innovation and investment in Australia’s complementary medicines industry; and

g)                make a number of minor amendments, principally to support timely access to therapeutic goods, improve consistency or make other more minor amendments and corrections.

Financial Impact Statement

The Australian Government is investing $7.7 million over four years (from the Therapeutic Goods Administration’s cash reserves) to establish a unique device identification database for medical devices. However, there is no direct cost associated with the amendments to the Act, as these would simply enable the establishment of the UDI system. There are no financial implications for the Government’s budget for all other measures, as implementation of these will be funded through the TGA’s current cost recovery mechanisms, under which the costs of administering the Act are fully recovered from industry.

Regulatory Impact Statement

Consistent with Regulatory Impact Statement (RIS) requirements, the Department certified that the Review of Medicines and Medical Devices Regulation (to which the UDI measure relates) undertook a process and analysis equivalent to a RIS. The Review of Medicines and Medical Devices Regulation report is annexed.

Statement of Compatibility with Human Rights

Prepared in accordance with Part 3 of the Human Rights (Parliamentary Scrutiny) Act 2011

THERAPEUTIC GOODS AMENDMENT (2020 MEASURES NO. 2) BILL 2020

This Bill is compatible with the human rights and freedoms recognised or declared in the international instruments listed in section 3 of the Human Rights (Parliamentary Scrutiny) Act 2011.

Overview of the Bill

The Therapeutic Goods Amendment (2020 Measures No. 2) Bill 2020 (the Bill) makes a number of amendments to the Therapeutic Goods Act 1989 (the Act).

These amendments will:

a)        address the availability of prescription medicines during medicine shortages by allowing pharmacists to substitute a different prescription medicine for one that a person has been prescribed, where the Minister has declared that there is a serious scarcity of the prescribed medicine and in accordance with the circumstances specified in the Minister’s declaration (in order to ensure the safe use of such substituted medicines);

b)       provide a legislative basis for the making of regulations to introduce a unique device identification database and related requirements for the improved traceability and monitoring of medical devices in Australia;

c)        allow APS employees in the Department of Health to obtain, possess or convey (or facilitate the conveyance of) goods for the purposes of identifying if the Act or regulations have been complied with, without contravening a law of the Commonwealth, a State, the Australian Capital Territory or the Northern Territory that prohibit such action except in certain circumstances (in particular, where a prescription has been issued in relation to the goods);

d)       allow the making of regulations to prohibit the import, export, supply or manufacture of therapeutic goods that are prohibited under an international agreement that Australia has ratified (in particular, it is expected that such regulations may relate to the prohibition of therapeutic goods that are mercury- added products prohibited under the Minamata Convention on Mercury that aims to protect both human health and the environment from anthropogenic emissions and releases of mercury and its compounds);

e)        enable the Secretary to consent to the importation and supply of therapeutic goods that do not have their registration or listing number on their label, to ensure that the civil penalties in the Act (subsections 19D(3) and (4) of the Act refer) for such importation and supply do not impede the timely availability of COVID-19 vaccines in Australia, some of which may not be able to meet this requirement (e.g. if they need to be stored at particularly low temperatures);

f)        improve the flexibility of the data protection scheme for assessed listed medicines, particularly by allowing sponsors and researchers to publish some information about their research without losing access to the scheme, and allowing medicines with the same indication but different active ingredients, to access data protection;

g)       enable APS officers in the Department of Health, and certain other officer holders, who are pharmacists to exercise powers to grant approvals to medical practitioners to supply unapproved therapeutic goods to their patients, to support access for Australians to this growing access pathway;

h)       clarify provisions relating to applications for the approval of new ingredients for use in listed and assessed listed medicines, principally to make it clear that an application lapses if the evaluation fee is not paid within the period prescribed in the regulations (this is designed to address situations where applicants submit an application but delay indefinitely paying the evaluation fee);

i)         permit the retention of material submitted with an application for the approval of a new ingredient or new indication for use in relation to listed and assessed listed medicines that has since been withdrawn (this is to assist with identifying any future safety issues);

j)         clarify that the power in section 7 of the Act to declare that goods are, or are not, therapeutic goods is legislative rather than administrative and may only apply in relation to classes of therapeutic goods, rather than individual products;

k)       as a consequence, focus the availability of review and appeal rights for decisions of the Secretary under section 7 on negative decisions of the Secretary in response to an application by a person (this would cover refusing to make, or refusing to vary or repeal, such a declaration), consistent with this power being legislative;

l)         allow the current Poisons Standard to be incorporated as in force from time to time in a range of legislative and administrative instruments made under the Act (e.g. permissions to refer to serious forms of diseases in a therapeutic goods advertisement), to streamline the making of such instruments and provide greater certainty for stakeholders through avoiding such instruments becoming rapidly out of date; and

m)      remove spent and redundant provisions and correct a heading.

Human Rights Implications

This instrument engages the right to health in Article 12 of the International Covenant on Economic Social and Cultural Rights (ICESCR), and the right to protection against arbitrary and unlawful interferences with privacy in Article 17 of the International Covenant on Civil and Political Rights (ICCPR).

Right to health

Article 12 of the ICESCR promotes the right of all individuals to enjoy the highest attainable standard of physical and mental health, and includes an obligation to take reasonable measures within available resources to progressively secure broader enjoyment of the right. In General Comment No.14: The Right to the Highest Attainable Standard of Health (Art. 12) (2000), the United Nations Committee on

Economic, Social and Cultural Rights states that health is a ‘fundamental human right indispensable for the exercise of other human rights’, and that the right to health is not to be understood as a right to be healthy, but includes the right to a system of health protection which provides equal opportunity for people to enjoy the highest attainable level of health.

The Bill takes several positive steps to promote the right to health, including in particular by introducing the pharmacist substitution measure, designed to help alleviate the effects of shortages of prescription medicines for Australian patients, reduce barriers to timely patient access to medicines and to better provide for continued access to medicines for all the patients who require medicines that are in short supply.

If a medicine is unavailable and the pharmacist is unable to contact the prescriber to authorise a change to the prescription, the patient may be unable to obtain their medicine, directly impacting their health through the interruption of treatment. In addition to this impact, the inability to access treatments may also cause considerable anxiety and stress for Australian patients. By enabling pharmacists to substitute a suitable alternative medicine that is available, in very limited circumstances which would not compromise patient safety, patients can continue to have access to their medication.

The Bill also supports the safety of Australian consumers in the use of medical devices in relation to amendments that would enable the regulations to provide for the establishment and maintenance of a UDI database to significantly improve the traceability of medical devices in Australia.

In particular, introducing UDI in Australia is expected to enable faster responses to safety issues, and more rapid and targeted recalls of defective medical devices, with the potential benefits for patients, healthcare providers and industry including:

·         more accurate recording and analysis of adverse events;

·         faster and more accurate identification of problems with devices, and more effective management of device recalls;

·         the ability to trace which medical device a particular patient has been implanted with or supplied;

·         reduced medical errors by enabling healthcare professionals to more precisely trace devices and obtain information on device characteristics; and

·         improved information-sharing on device issues on an international level and in relation to the management of global distribution chains.

The Bill also prohibits the import, export, supply and manufacture of goods containing substances that are prohibited in an international agreement. An international agreement anticipated to be included in the regulations for the purposes of this amendment to the Act is the Minamata Convention on Mercury. The Minamata Convention has an objective of protecting human health and the environment. There may, however, be other international agreements that the Australian Government seeks to ratify in the future relating to therapeutic goods.

The Bill also removes a possible impediment to the importation and supply of COVID-19 vaccines in Australia. The Act requires that registered or listed therapeutic goods (which would, in relation to registration, include any COVID-19 vaccines that are given marketing approval) that are imported into, or supplied in, Australia must have the registration or listing number for the goods set out on the label in the prescribed manner. Non-compliance would be a contravention of a civil penalty (subsections 19D(3) and (4) of the Act refer). Some COVID-19 vaccines may not have the registration number affixed to their label; for example, this may not be possible if they are required to be stored at particularly low temperatures. This may particularly be the case up to late 2021 given that such vaccines may be manufactured in multiple countries.

The Bill addresses this concern by enabling the Secretary to consent to importation and supply of registered or listed therapeutic goods notwithstanding non-compliance with this requirement. This would enable the Secretary to give such consent in relation to a vaccine for COVID-19 and avoid the risk that the civil penalties in the Act could delay the availability of COVID-19 vaccines in Australia. The AUST-R number, for a registered therapeutic good, can readily be made available for the benefit of health practitioners and consumers in other ways – for example publication on the Department’s website.

Right to protection against arbitrary and unlawful interferences with privacy

Article 17 of the ICCPR provides for the right not to be subjected to arbitrary or unlawful interference with privacy. The prohibition on interference with privacy prohibits unlawful or arbitrary interferences with a person’s privacy, family, home and correspondence. It also prohibits unlawful attacks on a person’s reputation.

Limitations on the right to privacy must be according to law and not arbitrary, i.e. they must be reasonable and necessary in the particular circumstances, as well as proportionate to the objectives they seek to achieve.

This Bill amends the Act to allow the regulations to provide for the establishment and maintenance of a database, which will store the unique device identifiers (broadly, combinations of numbers, symbols and letters) of medical devices, and related information, and to allow the regulations to include requirements relating to the inclusion of such identifiers, and the devices to which they relate, in the database.

The Bill prevents personal information being included in the database apart from information relating to the person in relation to whom the device is included in the Register, or their representative, or a representative of the manufacturer of the device. This information is needed to be included in the database so the manufacturer or person in relation to whom the device is included in the Register can be contacted if there are any safety issues identified.

In so doing the Bill engages Article 17 of the ICCPR.

It is important to note that any personal information provided for in regulations made for the purposes of the amendments introduced by the Bill must relate to a unique device identifier or a medical device to which such an identifier relates, or its import, export, manufacture or supply. It is also important to note that any such information must not include the personal information of patients.

Any such personal information that may be identified in the regulations as information that may be included in the database would be confined to the names of authorised representatives of medical device sponsors and manufacturers. This information will not be made public and the database will not include patient information.

As such, any interference with an individual’s privacy that may be said to be enabled by the Bill would not be an arbitrary interference within the meaning of Article 17, as:

·         the establishment and maintenance of the database is designed for a legitimate objective, in relation to improving the traceability of medical devices in Australia in order to better protect the safety of implanted patients and device users;

·         the personal information may only be included in the database where it relates to unique device identifiers, related devices or their import, export, manufacture or supply of those devices, and may not include patients’ personal information;

·         the Bill includes safeguards to allow the regulations to also provide for the removal from, or correction of information in, the database (this is not limited to personal information); and

·         while the Bill allows for the regulations to provide for the inclusion of limited personal information in the database, any proposed such regulations will be the subject of extensive and careful consultation (including with device sponsors and manufacturers), to ensure that any proposed inclusion of personal information is reasonable, necessary and proportionate. It is also noted that such regulations would, as a legislative instrument, be subject to the disallowance provisions of the Legislation Act 2003.

Accordingly, these amendments are reasonable, necessary and proportionate to achieving a legitimate objective of improving the traceability of medical devices and ensuring device manufacturers and sponsors can be contacted if rapid post-market action (including supply chain tracing and recalls) is required to address a safety issue.

Right to equality in the determination of criminal charges

Article 14 of the International Covenant on Civil and Political Rights (the ICCPR) guarantees equality before courts and tribunals, and, in the determination of criminal charges, or any suit at law, the right to a fair and public hearing before a competent, independent and impartial court or tribunal established by law. Those charged with a criminal offence have the rights set out in Article 14 of the ICCPR, including the presumption of innocence and the guarantees set out in Article 14(2). Under certain circumstances, a civil penalty can be characterised as ‘criminal’ for the purposes of the application of Article 14.

The amendments in this Bill include the introduction of offence and civil penalty provisions where a person imports, exports, manufactures or supplies therapeutic goods in contravention of a prohibition which gives effect to an international agreement.

The civil penalties introduced by the Bill would not appear to be characterised as ‘criminal’ for the purposes of Article 14. In particular, these civil penalties are clearly identified as being civil measures rather than criminal, and would be distinct in that regard from the range of clearly identified criminal offence provisions elsewhere in the Act. In addition, they do not carry any element of imprisonment for non-payment. As such, the civil penalties in the Bill would not appear to amount to criminal sanctions for the purposes of international human rights law.

The maximum level of the civil penalties involved – 300 penalty units for an individual and 3,000 penalty units for a body corporate – are also not as high as the maximum levels for many civil penalty provisions in the Act, which often have maximums of 5,000 penalty units for an individual and 50,000 for a body corporate.

The offence and civil penalty provisions in the Bill are principally intended to provide an effective deterrent to non-compliance, and to also reflect the serious potential impact on public health of non-compliance. These offences and civil penalty provisions reflect similar provisions in equivalent regulatory schemes for industrial chemicals and agricultural and veterinary medicines.

The amendments align with subsection 69C(5) of the Agricultural and Veterinary Chemicals (Administration) Act 1992, by making the maximum for the criminal offence 300 penalty units, and the civil penalty 300 penalty units for an individual and 3,000 penalty units for a body corporate. It also aligns with section 164 of the Industrial Chemicals Act 2019, which provides a maximum for contravention by a person of 300 penalty units for both the criminal offence and civil penalty.

The Bill does not contain any measures that would engage any other aspect of Article 14.

Conclusion

The Bill is compatible with human rights because it promotes the right to health, and because any engagement with the right to privacy is reasonable, necessary and proportionate.

The Hon Greg Hunt MP, Minister for Health

THERAPEUTIC GOODS AMENDMENT (2020 MEASURES NO. 2) BILL 2020 NOTES ON CLAUSES

Clause 1 – Short Title

This clause provides that the Bill, once enacted, may be cited as the Therapeutic Goods Amendment (2020 Measures No. 2) Act 2020.

Clause 2 – Commencement

This clause provides the timetable for the commencement of various provisions contained in the Bill:

·         sections 1 to 3 commence on the day that the Bill receives Royal Assent;

·         Schedules 1 to 4 and 7 to 10 commence on the day after the Bill receives Royal Assent; and

·         Schedules 5 and 6 commence 2 months after the Bill receives Royal Assent (to allow the making of regulations to support measures in these Schedules).

Clause 3 – Schedules

This clause provides that legislation that is specified in a Schedule to this Bill is amended or repealed as set out in the applicable items in the Schedule concerned, and any other item has effect according to its terms.

This is a technical provision which gives operational effect to the amendments contained in the Schedules. Schedules 1 to 10 amend the Therapeutic Goods Act 1989.

SCHEDULE 1—SUBSTITUTION OF PRESCRIPTION MEDICINE BY PHARMACISTS

Summary

Medicine shortages have become an increasing problem in recent years, for a number of reasons, including a decrease in local manufacturing, logistics problems and increases in demand. The Therapeutic Goods Administration (TGA) receives notifications of approximately 150 new medicine shortages every month. The problem of medicine shortages has been amplified as a result of the COVID-19 pandemic.

When a medicine is unavailable, community pharmacists have limited scope to substitute another medicine without the prior approval of the prescribing doctor. A pharmacist may substitute a different brand of an equivalent product, which may include an equivalent overseas-registered medicine approved for supply under section 19A of the Therapeutic Goods Act 1989 (the Act). However, where there is no equivalent available, the pharmacist cannot substitute a different medicine. If the pharmacist is unable to contact the prescriber to authorise a change to the prescription, the patient may be unable to obtain their medicine. This impedes timely patient access to medicines and risks interruption to treatment, which can impact patient health and also cause anxiety and stress.

An informal arrangement is currently in place between the Commonwealth and the States and Territories to allow pharmacist substitution of medicines that are in shortage, with patient consent. However, this informal arrangement is implemented through State and Territory legislation, and some State and Territory legislation currently allows for such provision to be made for pharmacist substitution but only during a public health emergency. A need has therefore arisen for a more streamlined, responsive pharmacist substitution scheme to help alleviate the effects of medicine shortages, that does not rely on State and Territory legislation and that reflects that medicine shortages may occur in a range of circumstances including circumstances other than where there is a public health emergency.

The pharmacist substitution scheme introduced by the amendments in this Schedule addresses such concerns by allowing pharmacists to substitute a medicine, in limited circumstances, during a serious scarcity of a medicine without the prior approval of the prescribing doctor. The Minister would have the power to declare that there is a serious scarcity of a particular medicine in Australia (or part of Australia), specify the medicine that pharmacists are permitted to dispense in substitution of the scarce medicine and relevant (principally safety-related) circumstances in which the substitution is permitted.

Therapeutic Goods Act 1989

Item 1 – At the end of subsection 4(1)

This item amends the objects of the Act (in subsection 4(1) of the Act) to introduce a new paragraph 4(1)(c) to make it clear that the objects of the Act include providing for the pharmacist substitution scheme to be introduced by this Schedule. This object

is not intended to extend beyond the pharmacist substitution scheme to govern other aspects of pharmacy practice.

Item 2 – After Division 2B of Part 3-2

This item introduces new Division 2C into Part 3-2 of the Act. Division 2C provides for the substitution of prescription medicines by pharmacists where there is a serious scarcity of a particular medicine.

In particular, this item introduces new section 30EK to the Act, which provides a power for the Minister to make a legislative instrument declaring a serious scarcity of specified medicine (“the scarce medicine”) across the whole or a specified part or parts of Australia, specifying the medicine (“the substitutable medicine”) that pharmacists are permitted to dispense in substitution for the scarce medicine and the circumstances in which that substitution is permitted.

Potential examples of such substitutions may include a medicine with the same active ingredients as the scarce medicine but:

·         a different strength, provided the dosage units of the substitutable medicine can be combined or divided to deliver an equivalent dosage regimen as the scarce medicine (e.g. 2x5mg tablets instead of 1x10mg tablet or half a 20mg tablet instead of a 10mg tablet); or

·         in a different dose form provided the substitutable medicine is to be administered by the same route of administration as the scarce medicine (e.g. a capsule instead of a tablet or a topical cream instead of a skin patch).

Alternatively, the substitutable medicine may also be a number of different medicines which, when taken together, have the same active ingredients as the scarce medicine, provided the dosage units of the substitutable medicines (taken together) can be combined or divided to deliver an equivalent dosage regimen as the scarce medicine.

Subsection 30EK(2) makes it clear that the Minister may only make an instrument under subsection 30EK(1) if satisfied:

·         that either the supply of the scarce medicine in Australia is not currently meeting the demand for that medicine for all of the patients in Australia who take that medicine, or that there is an imminent risk that supply will not, or will not be likely to, meet the demand for all patients who take, or may need to take the medicine (this is intended to cover both current and anticipated instances of scarcity, but not instances in the distant future);

·         that there is a significant risk of adverse health consequences for patients in Australia if those patients are unable to take the scarce medicine; and

·         of any other matters prescribed by the regulations (no such matters are initially envisaged, but this is designed to provide a capacity for the scheme to adapt flexibly to emerging safety concerns to protect patients’ health).

Subsection 30EK(3) makes it clear that the kinds of medicines that may be a scarce medicine or a substitutable medicine under the scheme are prescription medicines that contain a substance in Schedule 4 to the current Poisons Standard and that do not contain a substance in Schedule 8 to the current Poisons Standard.

Medicines with a Schedule 8 substance are higher risk medicines, subject to tighter supply controls, and are not considered suitable for substitution. It is likely that in practice the substitutable medicines would be medicines that are included in the Australian Register of Therapeutic Goods (“the Register”) or the subject of an approval in force under section 19A of the Act.

Subsection 30EK(4) provides that the circumstances in which the Minister may specify that substitution is permitted may relate to the class of persons for whom the substitutable medicine is suitable or not suitable. For example, the Minister may specify that substitution with the substitutable medicine is not suitable for paediatric use.

Under subsection 30EK(5), an instrument under subsection 30EK(1) remains in force for the period specified in the instrument, unless revoked before then. The specification of the period within which the instrument is in force means the instrument will be reviewed at that time in relation to whether there is a continuing need for the permissible substitution by pharmacists. However, if a serious scarcity is resolved before the end of the period, the instrument may be revoked sooner.

Subsection 30EK(6) defines a pharmacist for the purposes of section 30EK as a person registered as a pharmacist under a law of a State or Territory providing for the registration of pharmacists.

This item also introduces new section 30EL to the Act, which makes it clear that a pharmacist who, under a law of a State or Territory, is authorised to dispense prescription medicine, may do so to a person in accordance with an instrument that is in force under subsection 30EK(1), despite any law of a State or Territory.

Subsection 30EL(2) would provide that a pharmacist, for the purposes of this provision, is a person registered as a pharmacist under a law of a State or Territory providing for the registration of pharmacists.

Item 3 – After subsection 57(10)

This item would amend section 57 of the Act to insert subsection 57(10AA) which would limit the scope of delegations for the purposes of the pharmacist substitution scheme. Subsection 57(10AA) would provide that the power of the Minister under subsection 30EK(1) to make an instrument declaring a serious scarcity of a medicine and specifying substitutable medicine and related circumstances, may only be delegated to the Secretary or an SES employee or acting SES employee in the Department. This would include a Deputy Secretary, First Assistant Secretary or Assistant Secretary within the Department of Health, and reflects the significance of the instrument that would be made under section 30EK(1) in giving effect to this scheme and supporting continued access to prescription medicines balanced with any potential risks to patients.

SCHEDULE 2—UNIQUE DEVICE IDENTIFICATION

Summary

The Bill amends the Act to allow the making of regulations in relation to:

·         the establishment and maintenance of an Australian UDI database for medical devices (by the Secretary of the Department of Health or by other means such as a contractual arrangement);

·         the introduction of requirements for the inclusion of unique device identifiers and related information into the database (likely by medical device sponsors or manufacturers); and

·         the availability of the whole or a part of the database to the public or to specified persons, bodies or authorities (e.g. State or Territory health authorities).

The ‘unique device identifier’ of a medical device is broadly defined as any combination of numbers, symbols and letters given to the device to enable its identification (whether or not that combination also allows the identification of information relating to the device).

A number of other jurisdictions including the EU, the United States and Japan have implemented a UDI system or have commenced work on the implementation of such a system. It is intended that medical devices supplied in Australia (unless excluded) would be required to carry a unique device identifier. The current inability to trace which particular medical device has been implanted into or supplied to a particular patient has been a constraint on timely clinical and regulatory action in recent medical device safety crises, including safety issues associated with transvaginal mesh and textured breast implants.

Introducing UDI in Australia will improve the traceability and monitoring of medical devices, enabling faster responses to safety issues, and more rapid and targeted recalls of defective products. The potential benefits for patients, healthcare providers and industry include, for example:

·         more accurate recording and analysis of adverse events;

·         faster and more accurate identification of problems with devices, and more effective management of device recalls;

·         the ability to trace which medical device a particular patient has been implanted with or supplied;

·         reduced medical errors by enabling healthcare professionals to more precisely trace devices and obtain information on device characteristics; and

·         improved information-sharing on device issues on an international level and in relation to the management of global distribution chains.

Therapeutic Goods Act 1989

Item 1 – Subsection 3(1)

This item amends subsection 3(1) of the Act to make it clear that ‘personal information’ has the same meaning as in the Privacy Act 1988.

This item also amends subsection 3(1) to introduce a definition for ‘unique device identifier’ of a medical device. The new term would cover any combination of numbers, symbols and letters given to a medical device to enable its identification (whether or not that combination also allows identification of information relating to the device). This might possibly include, for example, a batch number, serial number, lot number or expiry date.

Item 2 – Section 41C

This item amends section 41C of the Act to expand the description of Part 4-2 of the Act, principally to reflect that the regulations that may be made under section 41CA of the Act may make provision for and in relation to the Secretary causing a database of unique device identifiers of medical devices to be established and maintained. The expanded description of Part 4-2 is to more accurately reflect the changes in the following items to Part 4-2 of the Act.

Item 3 – At the end of section 41CA

Subsections 41CA(1) and (2) of the Act provides that the regulations may set out requirements for medical devices, to be known as the essential principles. These are minimum benchmarks for the safety and performance of medical devices.

This item amends section 41CA to introduce new subsections (3)-(5) – principally to make it clear that the regulations made for the purposes of subsection 41CA(1) may include requirements in relation to the inclusion in the database of unique device identifiers of medical devices and information relating to those unique device identifiers, those medical devices or their import, export, manufacture or supply.

The purposes of a database of unique device identifiers of medical devices, is to enable improved traceability of medical devices. It will be very important in this regard for any information stored in the database to be accurate and complete, to support the integrity of the database. Accordingly, these amendments will enable the regulations to set out requirements relating to the inclusion of unique device identifiers and other information relevant to the devices to which they relate, in the database.

Subsection 41CA(4) makes it clear that new subsection 41CA(3) does not limit subsection 41CA(1) of the Act – that is, the regulations may set requirements for medical devices that are beyond the scope of new subsection 41CA(3). Subsection 41CA(5) makes it clear that subsection 41CA(3) does not limit subsection 41CA(1).

Item 4 – At the end of Part 4-2

This item adds a new division, Division 3—Database of unique device identifiers of medical devices, to Part 4-2 of the Act, comprising new section 41CE which deals with the database of unique device identifiers of medical devices.

Subsection 41CE(1) allows the making of regulations that may make provision for and in relation to the Secretary causing a database to be established and maintained. This enables the Secretary to establish and maintain the database herself or himself, or for the Secretary to otherwise cause the database to be established and maintained by another person. Subsection 41CE(1) also makes it clear that the database is to be

known as the Australian Unique Device Identification Database, or by a different name if one is prescribed by the regulations.

New subsection 41CE(2) highlights that the database must not include personal information, unless the personal information:

·         is the name of a person in relation to whom a medical device is included in the Register – this is principally where the person in relation to whom a device is included in the Register is an individual rather than a company or business; or

·         relates to an authorised representative of a medical device manufacturer or an authorised representative of a person in relation to whom a device is included in the Register.

This reflects that the information in the database will principally be focused on the medical devices themselves and related information, rather than on persons, but that these very specific instances of personal information will be important to include in the database in order to support the identification and traceability of medical devices and the ability to contact manufacturers and sponsors in relation to any safety concerns.

Subsections 41CE(3) and (4) enable the regulations to provide for the removal from, or correction of, information in the database, so that the regulations are able to include requirements to ensure that the information in the database is current, complete and accurate.

Subsection 41CE(5) enables the regulations to provide for the whole or a part of the database to be made publicly available, or made available to specified persons or authorities or bodies (e.g. State or Territory health departments, overseas regulators of therapeutic goods or research bodies).

Importantly, subsection 41CE(6) makes it clear that personal information covered by paragraphs (2)(b) or (c) – this is personal information related to authorised representatives of medical device manufacturers or sponsors – must not be made publically available as part of any exercise of the power in subsection 41CE(5).

Subsection 41CE(7) provides that, for the avoidance of all doubt, new subsections 41CE(2) to (6) do not limit subsection 41CE(1) which is the overarching authority for the regulations to make provision for and in relation to the Secretary causing the database of unique device identifiers of medical devices to be established and maintained, and subsection 41CE(8) makes it clear that the database of unique device identifiers of medical devices is not a legislative instrument.

Item 5 – After paragraph 41GT(e)

Section 41GS of the Act enables the Minister to exempt a kind of medical device from a number of specified parts or divisions of the Act (in particular, the requirement to be included in the Register) if satisfied that the kind of device is needed for stockpiling in preparation for a potential threat to public health or for use to deal with an actual threat to public health caused by an emergency that has occurred.

Section 41GT of the Act provides that an exemption under section 41GS is subject to any conditions specified in the exemption, if they relate to one or more of the matters listed in paragraphs 41GT(a)-(i).

This item amends section 41GT to include a new such matter in new paragraph 41GT(ea), relating to compliance with the requirements provided in the regulations under new section 41CA(3), i.e. in relation to unique identifiers. This will enable the Minister, when making an exemption under section 41GS of the Act, to include a condition relating to unique device identifiers for any such exempt devices, if the Minister wishes to do so.

SCHEDULE 3—PROTECTION FROM CRIMINAL RESPONSIBILITY

Summary

This Schedule amends the Act to enable TGA officers who are authorised persons to obtain and possess prescription medicines, or unapproved therapeutic goods, without contravening State and Territory laws.

Consumers are increasingly being lured to buy products which contain scheduled and often dangerous substances through retail outlets, such as sport supplement and sexual aid retailers, or online in circumstances where the consumer is not required to present a prescription or other documentation from a health professional. There are also increasing instances of products being offered for sale where the marketing and labelling does not disclose the inclusion of certain substances (or for which the marketing and labelling suggests that the products do not contain these substances) for which access is restricted at the Commonwealth, State and Territory level pursuant to the current Poisons Standard. An example is erectile dysfunction medication containing the Schedule 4 (prescription only medicine) substance sildenafil. This product is often traded in stores and online and may contain amounts of the active ingredient well above specified limits, or be counterfeit. Other examples include human performance products containing steroids and peptides, either disclosed on the label or concealed from labels. This presents a serious risk to Australian consumers, as it increases the risk of consumers using unsafe products, with no assurance as to their efficacy or safety.

Authorised persons under the Act are currently hindered in their ability to obtain and possess these products for laboratory testing to verify their compliance with regulatory requirements under the Act, as laws in a number of States and Territories in Australia include offences for an individual to obtain or possess an item containing a scheduled substance for which a prescription (or other authority) is required.

This Schedule amends the Act to address such concerns from a post-market monitoring perspective by enabling APS officers in the Department to obtain and possess prescription medicines, unapproved therapeutic goods or counterfeit therapeutic goods for the purpose of finding out if the Act or regulations have been complied with, without contravening State and Territory laws in doing so.

Therapeutic Goods Act 1989

Item 1 – After section 61A

This item introduces new section 62 to the Act, which provides that an APS employee in the Department who obtains, possesses or conveys or facilitates the conveyance of goods for the purposes of finding out whether the Act or the regulations has been complied with, is not criminally responsible for an offence against a law of the Commonwealth or a State or Territory law relating to the obtaining, possession, conveyance or facilitation of the conveyance of the goods.

The protection from criminal responsibility in subsection 62(1) would apply to the procuring of goods, possession of the goods and conveyance of the goods (i.e. where

the goods are transported or caused to be transported within Australia), where this occurs for the purpose of determining whether the Act and the regulations have been complied with. It applies to goods, instead of therapeutic goods, as it may not always be clear whether the goods are therapeutic goods or not without further examination of them. The protection from criminal responsibility is for an offence against a law of the Commonwealth or a State law, which is defined in section 3 of the Act as meaning a law of a State, of the Australian Capital Territory or of the Northern Territory.

Subsection 62(2) would extend the protection from criminal responsibility to another person who conveys the goods. For example, if the goods are obtained in Brisbane and an APS employee in the Department arranges for the goods to be transported to Canberra for testing to determine whether the goods comply with the Act or the regulations, the person transporting the goods, such as a courier, would not be criminally responsible for an offence under Commonwealth law or State law relating to possession or conveyance of the goods.

Item 2 – Application provision

This item would provide that section 62 of the Act, as inserted by this Schedule, only applies on or after the commencement of this item, i.e. it does not have retrospective effect.

SCHEDULE 4—INTERNATIONAL AGREEMENTS

Summary

The Minamata Convention on Mercury (the Minamata Convention) is an international agreement designed to protect human health and the environment from anthropogenic emissions and releases of mercury and its compounds, including in relation to the supply and trade of certain mercury-added products some of which are therapeutic goods. Australia has been a signatory to the Minamata Convention since 2013, but has not yet ratified it. Mercury is persistent, toxic and highly mobile in the environment once released, and is recognised as a substance producing significant neurological and other effects in humans, with concerns expressed in particular about the effects on unborn children and infants.

Before ratification of an international agreement like the Minamata Convention, Australia must be able to comply with its obligations under the agreement. The amendments to the Act in this Schedule are designed to create a preparedness for the anticipated ratification of the Minamata Convention, but to also put that level of preparedness in place for other possible future international agreements that also relate to therapeutic goods.

The amendments in this Schedule enable the making of regulations to prohibit the import, export, manufacture and supply of products containing substances that are prohibited or restricted under an international agreement that the Australian Government ratifies and which is also identified in regulations made for the purpose of these amendments. This is similar to the approach of other mechanisms in Commonwealth legislation, such as section 69C of the Agricultural and Veterinary Chemicals (Administration) Act 1992. This Schedule also includes a number of consequential amendments to the Act to ensure that such a prohibition or restriction is integrated into the regulatory scheme for therapeutic goods.

The amendments in this Schedule would not constitute a part of treaty action (i.e. implementing legislation for ratification) as the agreements do not refer to a specific international agreement but simply provide for the regulations to be amended to specify the relevant international agreement that Australia ratifies. The regulations would then become part of the treaty-making process and would be subject to the Joint Standing Committee on Treaties recommendation and the Australian Government decision to ratify.

Therapeutic Goods Act 1989

Item 1 – After Chapter 2

This item introduces new Chapter 2A to the Act, dealing with the prohibition on the import, export, manufacture or supply of therapeutic goods the subject of international agreements.

Section 9J provides a simplified outline of Chapter 2A.

Section 9K provides that if therapeutic goods are the subject of an international agreement prescribed for the purposes of new section 9K, the regulations may prohibit the import, export, manufacture or supply of such therapeutic goods or of therapeutic goods containing an ingredient or component that is the subject of such a prescribed international agreement. Under subsection 9K(5), the prohibition may be absolute, for example a complete prohibition on one or more of the import, export, manufacture or supply, or may be subject to such conditions as are prescribed.

Subsection 9K(8) provides that, without limiting subsection 9K(5), such conditions may confer on the Minister or Secretary a power to make a decision of an administrative character, refer to the Minister or Secretary as being satisfied of one or more specified matters or make provision for and in relation to the Minister or Secretary delegating powers to an SES employee in the Department. Subsection 9K(8) is intended to allow sufficient flexibility in the making of regulations to broadly cover future international agreements that Australian may ratify which relate to therapeutic goods.

However, before such regulations may be made, the Minister must be satisfied that the international agreement requires the parties to it to take steps to prohibit or restrict one or more of the import, export, manufacture and supply of the goods or of goods containing the ingredients or components (subsection 9K(4) refers) and the Minister must have caused to be published on the Department’s website a notice of the details of the international agreement, the proposed prohibition and the Minister’s satisfaction that the agreement requires parties to take steps to prohibit or restrict one or more of the import, export, manufacture and supply of the goods. The Minister must publish this notice at least 30 days before regulations are made.

Subsection 9K(7) precludes regulations containing a prohibition from commencing before the international agreement enters into force for Australia.

This item also introduces new section 9L, which provides targeted sanctions for non- compliance with a prohibition:

·         subsection 9L(1) introduces an offence if a person imports, exports, manufactures or supplies a therapeutic good in contravention of a prohibition in force under section 9K. The penalty for this offence would be 300 penalty units, which is commensurate with a comparable offence under the regulatory scheme for industrial, agricultural and veterinary chemicals (subsection 69C(5) of the Agricultural and Veterinary Chemicals (Administration) Act 1992 refers);

·         subsection 9L(2) introduces a civil penalty for the same, with a maximum civil penalty of 300 penalty units for an individual and 3000 penalty units for a body corporate, which is also commensurate with comparable civil penalties under the regulatory scheme for agricultural and veterinary chemicals.

In addition to maintaining consistency, these maximum penalty levels are designed to provide an effective deterrent to importing, exporting, supplying or manufacturing prohibited goods, and reflect the seriousness of such conduct particularly in relation to the potential risk to human health if a person were to be exposed to harmful prohibited substances, such as mercury, as a consequence of such action.

The maximum civil penalty of 3,000 for a body corporate in new subsection 9L(2) (and the body corporate multiplier that this represents) is consistent with the body corporate multiplier in other civil penalty provisions in the Act and reflects, in particular, the role of large companies in the Australian therapeutic goods market and the need for an incentive for therapeutic goods sponsors and manufacturers that are incorporated bodies to establish systems designed to avoid breaches of regulatory requirements. In so doing, the new civil penalty provisions contribute to the existing civil penalty scheme in the Act that is intended to prevent instances where public health and safety is, or could be, placed in jeopardy.

Consistent with a number of other offence and civil penalties in the Act (e.g. subsections 19B(7) and 19D(5)), new section 9M would provide that where importation or exportation of goods is an offence or contravenes a civil penalty provision under new section 9L, and the Secretary notifies the Comptroller-General of Customs that the Secretary wishes the Customs Act 1901 to apply to that importation or exportation, the Customs Act 1901 has effect as if the goods were goods described as forfeited to the Crown under section 229 of that Act as prohibited imports or prohibited exports. In practice, this would enable the Secretary to notify the Comptroller-General of importations or exportations of which the Secretary is aware, to prevent prohibited goods from being supplied in the Australian market or sent overseas.

Section 9N provides that Chapter 2A relies on the Commonwealth’s legislative power under paragraph 51(xxix) of the Constitution, i.e. the external affairs power, to give effect to an international agreement prescribed for the purposes of section 9K. This provision makes clear that the external affairs power provides the Constitutional basis for the introduction of the prohibition on the import, export, manufacture or supply of therapeutic goods to give effect to an international agreement.

Items 2 – 26 (amendments to sections 23B, 23C, 25, 26, 30, 30EA, 31, 32DA, 32DDA, 32DE, 32GA, 32HA, 32JA, 37, 38, 41, 41FD, 41GK, 41JA, 41KA and

introduction of new section 52G)

These items would amend the Act to make a number of consequential amendments to reflect the introduction of the prohibition mechanism in section 9K, principally to:

·         require that, as part of the preliminary assessment process (separate to this process for Class 1 biologicals), a statement from the applicant must accompany the application certifying that any imports, exports and supplies of the goods will not contravene the prohibition or a condition of such a prohibition (items 2, 3, 11, 12 and 21, relating to amendments to sections 23B, 23C, 32DDA and 41FD of the Act);

·         require an applicant for a manufacturing licence under Part 3-3 of the Act to provide a similar statement with their application, certifying (principally) that their proposed manufacturing in Australia will not contravene a prohibition or a condition of such a prohibition (item 18, relating to section 37 of the Act);

·         require or allow the Secretary to have regard to the potential for a contravention of the prohibition or condition (notwithstanding the making of a certification) as part of evaluating an application for registration, listing under section 26 of the Act or the inclusion of a biological other than a Class 1 biological in the Register (items 4, 5 and 13, relating to sections 25, 26 and 32DE of the Act);

·         allow the Secretary to have regard to the potential for a contravention of the prohibition (notwithstanding the making of a certification) when considering an application for a manufacturing licence under Part 3-3 of the Act (item 19, relating to section 38 of the Act);

·         require the Secretary to cancel the registration, listing or inclusion of therapeutic goods from the Register if satisfied that imports, exports or supplies of the goods would contravene the prohibition or a condition (items 6, 14 and 23, relating to sections 30, 32GA and 41GK of the Act) (in relation to the Convention this is expected to only impact a small number of products once regulations are in place, as there are only a small number of mercury-added products prohibited under the Convention that are in the Register – principally non-electric thermometers and sphygmomanometers (blood pressure monitors) and one topical antiseptic);

·         enable the Secretary to revoke or suspend a manufacturing licence under Part 3-3 of the Act if satisfied that the manufacture of the goods to which the licence relates would contravene the prohibition or a condition (item 20, relating to section 41 of the Act);

·         enable the Secretary to require a person to take certain kinds of action relating to the recall of therapeutic goods in relation to goods the supply of which contravenes the prohibition or a condition (items 8, 16 and 25, relating to sections 30EA, 32HA and 41KA of the Act);

·         enable the Secretary to require the provision of information or documents about whether any imports, exports or supplies of goods contravene the prohibition or condition (items 9, 10, 17 and 24, relating to sections 31, 32JA and 41JA of the Act); and

·         preclude the use of the powers to exempt therapeutic goods from the requirement to be entered in the Register, and the pathways for accessing unapproved therapeutic goods, in the Act, to exempt, approve or authorise goods that are the subject of a prohibition (where there is a prohibition in place that is subject to conditions, the use of these powers to exempt, approve or authorise such goods would be precluded except where such action is subject to conditions that are consistent with the conditions relating to the prohibition) (item 26, relating to new section 52G).

Items 27 to 30 – Application provisions—registration or listing of therapeutic goods, biologicals, manufacturing of therapeutic goods and medical devices These items provide for the application of the provisions in this Schedule. The amendments in this Schedule are not intended to have retrospective effect and, therefore, only apply to applications made on or after the commencement of this Schedule or action to be taken after the commencement of this Schedule. That is, they would only apply to applications for listing, registration or inclusion in the Register made on or after the commencement of this Schedule and to post market actions (such as requests for information, cancellation from the Register or recall action) taken after the commencement of this Schedule.

SCHEDULE 5—RESTRICTED INFORMATION

Summary

A data protection scheme for assessed listed medicines was introduced to the Act by the Therapeutic Goods Amendment (2020 Measures No. 1) Act 2020, to encourage and incentivise innovation in the complementary medicines industry by protecting clinical trial results and preventing the Secretary from having regard to it in evaluating a subsequent application. This effectively prevents competitors from seeking market authorisation of generic forms of an assessed listed medicine – competitors will be unable to rely on data generated by the sponsor of the innovator medicine for 5 years after the listing of the innovator medicine.

Since the scheme’s introduction industry have raised a number of concerns in relation to the operation of the scheme, including that it does not reflect the range of products and the range of innovations that may relate to the products for which the assessed listed pathway may be used, and does not allow researchers or sponsors to publish certain information relating to their research.

This Schedule makes a number of amendments to the scheme to address some of these issues, in particular, to improve the flexibility and breadth of the scheme.

Therapeutic Goods Act 1989

Item 1 – Paragraphs 26AF(2)(b), (c) and (d)

This item amends section 26AF of the Act to clarify a number of aspects of the meaning of ‘restricted information’ for the purposes of the data protection scheme for assessed listed medicines.

In particular, item 1 would substitute new subparagraphs 26AF(2)(b), (c), (d), and (da) for the current paragraphs 26AF(2)(b), (c) and (d), with the following main effects for an assessed listed medicine to be able to access the data protection scheme for such products:

·         applications for listing in the Register of such a medicine must include the trial number of the clinical trial to which the information they are seeking data protection for relates;

·         the Secretary must be satisfied that the trial number is included in a clinical trial registry prescribed for the purposes of new subparagraph 26AF(2)(b)(ii);

·         the indication for the medicine must be of a kind that is appropriate for such products, and not an indication that would be made available for general use for all listed medicines – in practice such indications are referred to as “intermediate indications” and relate to preventing, curing or alleviating a disease, ailment, defect or injury other than one that, under the Therapeutic Goods Advertising Code (the Code) is a serious form; or to use in connection with alleviating a disease, ailment, defect or injury that would, under the Code, be a serious form (an example of the latter would be an indication relating to the use of a medicine to alleviate the symptoms or effects of a serious disease such as the alleviation of dehydration associated with gastroenteritis);

·         ensuring that a person could not lose data protection through another person applying for the inclusion of the same indication in the Ministerial determination made under paragraph 26BF(1)(a) of the Act which authorises the general use of indications for all listed and assessed listed medicines; and

·         allowing medicines with the same indications, but different active ingredients, to access data protection.

Item 2 – After paragraph 26AF(2)(e)

Currently under section 26AF of the Act, for a sponsor to access the data protection scheme in relation to clinical trial information that relates to their assessed listed medicine, the information must not be available to the public.

This has the effect of precluding the publication of any such information, before or after the medicine is listed in the Register. Stakeholders have raised concerns that this is unduly restrictive, for both industry and researchers who may undertake clinical trial research on behalf of or in conjunction with sponsors seeking to innovate.

This item introduces paragraph (eb) in subsection 26AF(2) to address such concerns, principally by:

·         focusing the time during which the information must not be available to the public to the period from the day the application for listing for the medicine was made to the end of the day before the medicine was listed in the Register – this limits the period in which the information must not be available to the public to the application and evaluation period for the medicine; and

·         only requiring information other than information about the clinical trial that is included in a prescribed clinical trial registry to not be available to the public – this means that a subset of information about the research will be able to be made public through such a registry which is often required to undertake a clinical trial.

This item also introduces paragraph (ea) to require that for information relating to an assessed listed medicine to be restricted information under the scheme, it must have been relied upon by the Secretary in deciding to list the medicine. If the information was not relied upon (e.g. perhaps it did not provide sufficient evidence to support listing or was not relevant), then the information will not be restricted information.

Item 3 – At the end of section 26AF

This item introduces subsection (3) at the end of section 26AF, which would provide that a registry prescribed for the purpose of subparagraph 26AF(2)(b)(ii) may be a registry established within or outside Australia (i.e. it does not have to be an Australian registry) and must be a registry that is accessible by the public (i.e. a member of the public would be able to access the registry for free online).

Item 4 – Application provision

This item provides that the amendments in this Schedule apply to an application made on or after the commencement of this item, i.e. these amendments do not have retrospective effect.

SCHEDULE 6—VARIATION OF PERMISSIBLE INGREDIENTS DETERMINATION

Summary

This Schedule makes a number of amendments to section 26BE of the Act to clarify provisions relating to variation of the permissible ingredients determination made under section 26BB of the Act.

Therapeutic Goods Act 1989

Item 1 – At the end of section 26BDA

This item amends section 26BDA to insert paragraph (c) which provides another situation in which an application under section 26BD to vary the permissible ingredients determination under section 26BB of the Act lapses. Paragraph 26BDA(c) would provide that an application to vary the permissible ingredients determination would lapse where the evaluation fee prescribed for such applications has not been paid before the period worked out in accordance with the regulations. A consequential amendment to the regulations is proposed to provide a timeframe for the payment of an evaluation fee for such applications – if the evaluation fee is not received within that timeframe, the application will lapse.

There have been situations where an applicant submits an application but does not pay the prescribed evaluation fee for weeks or even months, significantly delaying the evaluation of the application. This is also problematic where the TGA receives multiple applications for the same ingredient from applicants seeking market exclusivity. Such applications are evaluated in the order in which the applications are received, provided the applications pass preliminary assessment, therefore delayed payment of an evaluation fee will delay evaluation of all subsequent applications relating to that ingredient.

Items 2 to 7 – Paragraphs 26BE(5B)(b) and (c), paragraphs 26BE(5C)(a) and (b), subsection 26BE(5D) and paragraph 63(2)(daaa)

These items amend paragraphs 26BE(5B)(b) and (c), paragraphs 26BE(5C)(a) and (b), subsection 26BE(5D) and paragraph 63(2)(daaa) to refer to a decision under paragraphs 26BE(4)(a) or (b), to clarify that this includes both a recommendation or refusal to make a recommendation.

Item 8 – Application provision

This item provides that the amendments in this Schedule apply to an application made on or after the commencement of this item, i.e. these amendments do not have retrospective effect.

SCHEDULE 7—DELEGATION

Summary

The Secretary’s powers under subsection 19(5) of the Act, giving effect to the Authorised Prescriber Scheme, may currently only be delegated to a departmental officer who is a medical or dental practitioner. The proposed amendments in this Schedule would enable departmental officers who are pharmacists to be delegates for the making of decisions to authorise medical practitioners to supply unapproved medicines to patients as an Authorised Prescriber.

The expansion of the subsection 19(5) delegations to such pharmacists is designed to ensure that there are a sufficient number of delegates able to exercise the Secretary’s powers under subsection 19(5) for all Authorised Prescriber applications received or expected to be received. There has been a significant increase in the number of Authorised Prescriber applications the TGA has received from January to June 2020 so far compared to July to December 2019, and this is expected to continue to increase.

It is considered appropriate for pharmacists to make decisions under subsection 19(5) in relation to medicines as the decisions relate to the authorising of medical practitioners to supply particular medicines to patients.

Therapeutic Goods Act 1989

Item 1 – After subsection 57(5)

This item introduces subsection (5A) in section 57 of the Act to enable the power of the Secretary under subsection 19(5) to be delegated to a person registered, or eligible to be registered, in a State or internal Territory as a medical or dental practitioner or a pharmacist. This only relates to decisions about supply of a medicine under the Authorised Prescriber scheme, not a biological or medical device.

Item 2 – Subsection 57(6)

This item amends subsection 57(6) to remove the reference to section 19(5) as subsection 57(5A) as inserted by this Schedule deals with delegations of the power in section 19(5).

Item 3 – Saving provision

This item provides that the amendments in this Schedule do not affect the validity of an instrument in force under subsection 57(1) of the Act before the commencement of this item.

SCHEDULE 8—RETENTION OF MATERIAL ON WITHDRAWAL OF APPLICATION

Summary

This Schedule makes amendments to section 53 of the Act to include updated application types.

Therapeutic Goods Act 1989

Item 1 – After paragraph 53(b)

This item introduces subparagraphs 53(baa) and (bab) into the Act to include references to applications to vary the section 26BB determination and applications to vary the section 26BF determination. These applications types have more recently been included in the Act and were not reflected in section 53.

Item 2 – Application provision

This item provides that the amendments made by this Schedule apply on or after the commencement of this item, i.e. it does not have retrospective effect.

SCHEDULE 9—CONSENTS TO IMPORTATIONS OR SUPPLIES OF THERAPEUTIC GOODS

Summary

This Schedule amends section 19D of the Act to remove a potential impediment to the importation and supply of COVID-19 vaccines in Australia.

Subsections 19D(3) and (4) of the Act set out civil penalties for the importation into, or supply in, Australia of registered or listed therapeutic goods that do not have their registration (AUST-R) or listing number (AUST-L) on their label.

Inclusion of the AUST-R may not be possible for some COVID-19 vaccines, for example if they are required to be stored at particularly low temperatures or if it is not possible to include the number when they are manufactured in another country.

To ensure that the civil penalties in the Act do not inadvertently impede or preclude the timely availability of COVID-19 vaccines in Australia, the amendments in this Schedule amend section 19D to enable the Secretary to consent to the importation and supply of registered (or listed) therapeutic goods notwithstanding non-compliance with the requirement to include the registration (or listing) number on the label.

Although this measure is being implemented principally to address the current need to safeguard the capacity for importation and supply of COVID-19 vaccines in Australia, it is anticipated that, in the future (other than in relation to COVID-19), such consents will principally be appropriately targeted at circumstances where there is a national public health emergency, for example a pandemic as declared by the WHO. It may also be likely that this power would principally be delegated to the Deputy Secretary classification level and that consideration would be given to limiting any consent for a short period of up to 6 to 12 months.

It is also important to note that if the Secretary grants such a consent, it would still be possible to ensure that the public can be made aware of the registration or listing number of goods covered by such a consent, as registration or listing numbers could be published on the TGA’s website and the information circulated to health practitioners and consumers. 

Therapeutic Goods Act 1989

Items 1 and 2 – After paragraphs 19D(3)(b) and 19D(4)(b)

These items would amend section 19D of the Act to introduce new paragraphs 19D(3)(ba) and 19D(4)(ba), modifying the terms of the civil penalty provisions in subsections 19D(3) and (4) of the Act for importing and supplying registered or listed therapeutic goods that do not include their registration or listing number on their label by allowing the Secretary to consent to the importation or supply of such goods notwithstanding that they do not contain this information on their label.

The effect of the amendments is that the civil penalty will not apply where the Secretary has granted such consent. Review and appeal rights would apply to a decision of the Secretary in this regard.

Item 3 – At the end of section 19D

This item amends section 19D of the Act to introduce a requirement for the Secretary to, as soon as practicable after making a decision to give a consent mentioned in subsection 19D(3) or (4), cause particulars of the decision to be published on the Department’s website.

This item also requires the Secretary to, within 28 days after making a decision to refuse to grant such a consent, notify the applicant in writing of the decision and the reasons for it.

Item 4 – After subsection 56(4)

This item makes a minor, consequential amendment to section 56 of the Act to provide that, in any civil penalty proceedings under subsections 19D(3) or (4) of the Act, a certificate by the Secretary to the effect that the Secretary had not granted a consent under those provisions is prima facie evidence of the matters specified in the certificate.

Item 5 – Application provisions

This item sets out that the amendments to subsections 19D(3) and (4) of the Act made by this Schedule apply in relation to importations and supplies that occur on or after the commencement of this item.

SCHEDULE 10—OTHER AMENDMENTS

Summary

This Schedule makes minor amendments to the Act to provide that the declared goods order, declaring that goods are or are not therapeutic goods, is a legislative instrument and to enable the Poisons Standard to be referred to in other instruments as in force from time to time.

The amendments reflect the proper nature of a declaration made under section 7 of the Act as a legislative instrument. The amendments would also ensure that a declaration under section 7 applies in relation to classes of therapeutic goods, not “particular goods”, and so has broad universal impact, consistent with subsection 8(4) of the Legislation Act 2003. The amendments would assist with reinforcing the nature of the legislative power (which supports the consistent and universal regulation of therapeutic goods) and confirm that the power must be exercised uniformly, not disadvantaging any particular persons or goods. A consequential amendment would also be made to subsection 60(1) of the Act to clarify that the initial decision relates to the refusal of an application made by a person under subsection 7(2). Such an application might request the making, variation or repeal of a declaration made under section 7. The amendment would therefore have the same material effect as is presently the case under section 60 of the Act.

The amendments enable the current Poisons Standard to be incorporated by reference as in force or existing from time to time, in all legislative, notifiable and administrative instruments made under the Act. The current Poisons Standard is a non-disallowable legislative instrument made under section 52D of the Act. The instrument reflects decisions of the Secretary regarding the classification of medicines and poisons into different schedules, which indicate the degree of risk associated with these substances and the controls recommended to be exercised over their availability. State and territory legislation references the current Poisons Standard for the purpose of specifying restrictions on the access, possession, supply, storage and transportation of substances. Commonwealth legislation similarly references the current Poisons Standard for regulatory and enforcement purposes, and there are numerous instruments made under the Act that refer to the current Poisons Standard.

As a consequence of not being disallowable, the current Poisons Standard is not able to be adopted or incorporated as in force from time to time in accordance with subsection 14(2) of the Legislation Act 2003 and subsection 46AA(2) of the Acts Interpretation Act 1901. This has meant that the dynamic meaning given to the ‘current Poisons Standard’ in the Act and Regulations is not consistently applied through all instruments made under the Act. This amendment would ensure that the term ‘current Poisons Standard’ (as defined in the Act) has the same meaning as in the Act (and the regulations) as in all other instruments made thereunder, consistent with paragraph 13(1)(b) of the Legislation Act 2003 and paragraph 46(1)(b) of the Acts Interpretation Act 1901. It would enable the one version of the Poisons Standard to be referenced, being the current Poisons Standard registered on the Federal Register of Legislation as in force from time to time, rather than multiple different versions depending on the date on which the relevant instrument commenced.

The amendment would therefore provide uniformity, consistency and certainty with respect to the characterisation and regulation of therapeutic goods throughout Australia.

Therapeutic Goods Act 1989

Items 1, 3 and 4 – Subsection 7(1), subsection 7(1A) and paragraph 7(4)(a)

These items amend subsections 7(1) and 7(1A) and paragraph 7(4)(a) to remove the reference to ‘particular goods’, thus ensuring that a declaration made under subsection 7(1) applies only in relation to classes of goods. Such an instrument would have the direct or indirect effect of affecting privileges or interests, imposing obligations or varying or removing obligations within the meaning of subsection 8(4) of the Legislation Act 2003. Accordingly, these amendments would assist with reinforcing the nature of the legislative power (which supports the consistent and universal regulation of therapeutic goods) and confirm that the power must be exercised uniformly, not disadvantaging any particular persons or goods.

Item 2 – Subsection 7(1)

This item amends subsection 7(1) to provide that an order made under that subsection, declaring that goods are or are not therapeutic goods, is a legislative instrument consistent with subsection 8(4) of the Legislation Act 2003. The characterisation of an order made under subsection 7(1) as a legislative instrument would ensure that the order is subject to the usual consultation requirements and disallowance provisions applying to legislative instruments under the Legislation Act 2003, as is appropriate for the proper and transparent regulation of therapeutic goods in Australia.

Consequently, a declaration made under section 7(1) would be subject to public and parliamentary scrutiny in addition to the review rights afforded under section 60.

Item 5 – Section 41HB (heading)

This item makes a minor amendment to the heading of section 41HB to clarify that section 41HB relates to approvals granted for use of therapeutic goods for special and experimental uses that are not included in the Register.

Item 6 – Section 52EC

This item repeals section 52EC and inserts new section 52F into the Act.

Section 52EC of the Act requires that an independent panel review the operation of the scheduling regime under Part 6-3 of the Act and give the Minister a written report. The review must have commenced by 1 July 2013 and be completed within 6 months. Accordingly, this provision is now redundant.

Section 52F provides that the current Poisons Standard may be incorporated by reference, as in force or existing from time to time, in all legislative, notifiable and administrative instruments made under the Act, despite subsection 14(2) of the Legislation Act 2003 and subsection 46AA(2) of the Acts Interpretation Act 1901.

The current Poisons Standard is a non-disallowable legislative instrument made under section 52D of the Act. It is published on the Federal Register of Legislation and therefore freely available. The instrument reflects decisions of the Secretary regarding the classification of medicines and poisons into different schedules. The schedules indicate the degree of risk associated with these substances and the controls recommended to be exercised over their availability. State and Territory legislation references the current Poisons Standard for the purpose of specifying restrictions on the access, possession, supply, storage and transportation of substances.

Commonwealth legislation similarly references the current Poisons Standard for regulatory and enforcement purposes. Notably, there are numerous instruments made under the Act that refer to the current Poisons Standard, including the Regulations, which characterise therapeutic goods with reference to substances included in one or more schedules of the current Poisons Standard in order to distinguish between those therapeutic goods that require registration and those therapeutic goods that require listing (see Schedule 4 to the Regulations).

The item enables the incorporation by reference of the current Poisons Standard from time to time in all legislative, notifiable and administrative instruments. It would therefore ensure that the dynamic meaning given to the ‘current Poisons Standard’ in the Act and Regulations (sections 3 and 52A of the Act refer) is consistently applied in all other instruments made thereunder, in accordance with paragraphs 13(1)(b) of the Legislation Act 2003 and 46(1)(b) of the Acts Interpretation Act 1901.

This will mean that any reference to the current Poisons Standard in legislative, notifiable or administrative instruments made under the Act would indeed be a reference to the current instrument registered on the Federal Register of Legislation as in force from time to time, and will enhance uniformity, consistency and certainty with respect to the characterisation and regulation of therapeutic goods throughout Australia.

Item 7 – Subsection 60(1) (paragraph (a) of the definition of initial decision)

This item replaces paragraph 60(1)(a) of the Act to provide that a decision to refuse to make, or vary or repeal, a declaration under section 7 upon an application made under subsection 7(2) is an initial decision that may be subject to review under section 60.

The amendment is ancillary and consequential to the amendments made by items 1 to 4 and would clarify the existing review rights in section 60 of the Act for decisions made under subsection 7(1) by articulating those rights with reference to applications made by interested persons under subsection 7(2). It would reflect that the initial decision in section 60 is better characterised as a refusal to make a favourable decision in response to an application to make a declaration, or in relation to a declaration that has been made by the Secretary, an application to vary or repeal that declaration.

The amendment does not interfere with review rights relating to declarations made under section 7, but rather clarifies that the initial decision relates to the refusal of an application made by a person under section 7(2). If the application relates to goods that were not previously declared and the Secretary agreed with the application, then the Secretary would take steps to make a legislative instrument subject to any further public consultation. If the Secretary did not agree with the application, then the application would be refused and the person would be entitled to seek review under section 60 in relation to that refusal.

A person who is aggrieved by the making of a declaration would be entitled to apply to the Secretary under section 7(2) to have that declaration varied or repealed (as is presently the case). A decision to refuse that application would similarly be reviewable under section 60. The initial decision would be the refusal of the application made under section 7(2) rather than the making (and registration) of the legislative instrument itself under section 7(1). Any decision on reconsideration that

necessitates the making, variation or repeal an existing declaration would be progressed legislatively in accordance with the Legislation Act 2003.

Item 8 – Subsection 60(1) (after paragraph (d) of the definition of initial decision) This item makes a consequential amendment as a result of item 7 and introduces in subsection 60(1) a reference to a decision under subsection 41BD(3) in the definition of initial decision.

Item 9 – Saving provisions

Subitem 9(1) provides that the amendments made by this schedule do not affect the validity of an order in force under section 7 of the Act before the commencement of this item.

Subitem 9(2) provides that section 60 as in force prior to the commencement of this item continues to apply to a decision made before that commencement, i.e. the amendments to section 60 in this Schedule do not have retrospective effect.

Deputy Secretary

Executive Director

Office of Best Practice Regulation

Department of the Prime Minister and Cabinet

1 National Circuit

BARTON  ACT  2600

Email: helpdesk-OBPR@pmc.gov.au

Dear Mr Lange

Certification of independent review: Review of Medicines and Medical Devices Regulation

I am writing to certify that the attached independent review of the Therapeutic Goods Administration’s regulation of medicines and medical devices has undertaken a process and analysis equivalent to a Regulation Impact Statement (RIS).

I certify that this document adequately addresses all seven RIS questions, and is submitted to the Office of Best Practice Regulation for the purposes of introducing a power in the Therapeutic Goods Act 1989 to allow the making of regulations to provide for an Australian unique medical device identifier (UDI).

Specifically, the independent review (pg 128 of Stage 1 report) confirmed that “introducing this requirement (i.e.: for an UDI)…. at the beginning of the regulatory process will not present an additional Australian regulatory burden”.

I am satisfied that the scope of the problem and the recommendations identified in the certified review including Recommendation 20 – the regulation of medical devices by the Australia National Regulatory Authority is, wherever possible, aligned with the European Union Framework (OBPR Reference 24696)) are substantially the same as the identified problem and recommendations in the policy proposal.

I note that the implementation of this proposal will not increase the regulatory burden to business, community organisations or individuals due to the adoption of the UDI being a global requirement of countries from where the majority of medical devices are manufactured and imported for supply in Australia.

Phone: (02) 6289 4200 Email: John.Skerritt@health.gov.au PO Box 100 Woden ACT 2606 - www.health.gov.au

- 2 -

Accordingly, I am satisfied that the attached report is consistent with the Australian Government Guide to Regulatory Impact Analysis.

Yours sincerely

Adj. Professor John Skerritt

Health Products Regulation Group    05 June 2020

Expert Panel

Review of Medicines and Medical Devices Regulation

Report to the Minister for Health on the Regulatory Framework for Medicines and Medical Devices

31 March 2015

Emeritus Professor Lloyd Sansom AO Mr Will Delaat AM

Professor John Horvath AO

The Hon Sussan Ley MP Minister for Health Parliament House CANBERRA ACT 2600

Dear Minister Ley

The Independent Panel for the Review of Medicines and Medical Devices Regulation is pleased to present its Report on the first stage of the Review. In accordance with the Review’s Terms of Reference, this Report examines and makes high level recommendations on the regulatory frameworks for medicines and medical devices, as well as on access to unapproved therapeutic goods in special circumstances. The Report makes recommendations on supporting infrastructure necessary to facilitate the implementation of the recommendations. Further, the Panel has identified and addressed a number of related issues within the text of the Report.

The Panel is mindful of the technological change and innovation that has occurred in the changing health care environment since the regulatory frameworks for medicines and medical devices were conceived. In framing its recommendations, the Panel has endeavoured to ensure that the National Regulatory Authority has the necessary tools, flexibility, and legislative underpinning to respond effectively to future challenges. This will ensure that it can maintain its place as a regulator that is highly regarded both nationally and internationally.

In undertaking the Review, the Panel sought comment regarding the regulation of medicines and medical devices from stakeholders over the November 2014 to January 2015 period, receiving over 100 submissions from consumers, industry and health professionals. In addition, a number of face- to-face and teleconference consultations were held, which were well attended by stakeholders.

The Panel has commenced work on Stage Two of the Review, examining the regulation of complementary medicines, with the release of a supplementary chapter to the Discussion Paper and a call for submissions on 20 February 2015. The Panel will also report on the regulation of  advertising of therapeutic goods in Stage Two, to allow a single, whole-of-industry report, to be presented.

The Panel intends to present its Stage Two Report to Government mid-2015. Yours sincerely

31 March 2015

cc:           The Hon Tony Abbott MP, Prime Minister

The Hon Christian Porter MP, Parliamentary Secretary to the Prime Minister Senator the Hon Fiona Nash, Assistant Minister for Health

ACKNOWLEDGEMENTS

The Panel would like to acknowledge the following people and organisations for their contribution throughout this process:

Therapeutic Goods Administration

The Panel would like to thank Adjunct Professor John Skerritt and the staff of the TGA for their openness in engaging with the Panel and for their timely responses to the Panel’s many requests for information.

Secretariat Services

The Panel wishes to acknowledge the excellent support that it received from the secretariat in the management of the Review and in the preparation of the Review report:

Department  of  Health  -  Ms  Cheryl  Wilson,  Ms  Michelle   Palombi,  Ms  Fran   Verass,   Mr Thomas Ashby, Ms Danielle Dalton, Mr Jonathan Ayre and Ms Julie Dennett.

Stakeholders

The Panel would also like to thank all the stakeholders and individuals who provided submissions for the Review, and to all those who attended the consultation forums.

TABLE OF CONTENTS

Acknowledgements................................................................................................................... iii

Therapeutic Goods Administration....................................................................................... iii

Secretariat Services.............................................................................................................. iii

Stakeholders.......................................................................................................................... iii

Executive Summary.................................................................................................................. vii

Recommendations.................................................................................................................... ix

Glossary of Abbreviations....................................................................................................... xxv

Chapter One: Background to the Review.................................................................................. 1

1.1  Objective of the Review................................................................................................... 1

1.2  Terms of Reference......................................................................................................... 1

1.2.1  Additional requirements........................................................................................... 3

1.3  Timeframe for the Review.............................................................................................. 3

1.4  The Review Panel............................................................................................................. 4

1.5  Review Secretariat........................................................................................................... 4

1.6  Review Methodology....................................................................................................... 4

1.6.1  Principles underpinning the Review......................................................................... 5

1.6.2  Discussion papers...................................................................................................... 6

1.6.3  Submissions............................................................................................................... 6

1.6.4  Consultations............................................................................................................. 7

Chapter Two: Overview............................................................................................................. 9

Chapter Three: Introduction.................................................................................................... 15

3.1  National Regulatory Authority....................................................................................... 16

3.1.1  Australian Register of Therapeutic Goods (ARTG)................................................. 17

3.1.2  Funding.................................................................................................................... 17

3.1.3  TGA performance................................................................................................... 18

3.2  Medicines....................................................................................................................... 19

3.2.1  Timeliness of approvals.......................................................................................... 19

3.2.2  Would use of overseas assessment reports improve timeliness?.......................... 22

3.2.3  Would use of overseas assessment reports reduce duplication?........................... 26

3.3  Medical Devices............................................................................................................. 27

3.3.1  Timeliness of approvals.......................................................................................... 28

3.3.2     Would use of overseas assessment reports improve timeliness and reduce duplication?    30

3.4  Use of overseas assessments......................................................................................... 32

3.4.1  Independent capacity to undertake assessments and make decisions.................. 33

Chapter Four: Regulatory Framework for Medicines.............................................................. 39

4.1  Current regulation of medicines................................................................................... 39

4.1.1  Risk-based framework............................................................................................ 40

4.2  Assessment of current regulatory framework.............................................................. 44

4.3  Proposed reforms to the regulatory framework for medicines.................................... 45

4.3.1  Pre-market assessment of new chemical entities.................................................. 45

4.3.2  Pre-market assessment of generic medicines and biosimilars.............................. 51

4.3.3  Implementation of Pathway Two............................................................................ 54

4.3.4  Features of Pathway Three - expedited approval................................................... 66

4.3.5  Enhanced transparency of scheduling processes................................................... 74

4.3.6  Scheduling and the advertising of medicines......................................................... 80

4.3.7  Post-market regulation........................................................................................... 86

4.3.8  Low-risk therapeutic goods..................................................................................... 89

Chapter Five: Regulatory Framework for Medical Devices.................................................... 95

5.1  Current Regulation of Medical Devices........................................................................ 95

5.1.1  Risk-based regulatory framework.......................................................................... 96

5.1.2  Pre-market assessment of medical devices........................................................... 99

5.1.3  Post-Market Monitoring....................................................................................... 101

5.1.4  Advertising of Medical Devices............................................................................ 102

5.2  Assessment of Current Regulatory Framework........................................................... 103

5.3  Proposed reforms to the regulatory framework for medical devices........................ 104

5.3.1  Multiple Pathways for inclusion of a device in the ARTG..................................... 106

5.3.2  Reduced complexity through international harmonisation.................................. 120

5.3.3  Enhanced transparency of processes and timeframes......................................... 124

5.3.4  Post-market monitoring........................................................................................ 125

5.3.5  Threshold issues for ‘devices’............................................................................... 129

Chapter Six: Access to Unapproved Therapeutic Goods........................................................ 133

6.1  The Special Access Scheme......................................................................................... 134

6.1.1  The process for accessing unapproved therapeutic goods under the Special Access Scheme         135

6.1.2  Issues raised in relation to the Special Access Scheme........................................ 136

6.1.3  The use of the SAS to address medicine shortages.............................................. 143

6.2  The Authorised Prescriber Scheme............................................................................. 145

6.3  Clinical Trials (CTN and CTX)....................................................................................... 147

6.4  Importation for Personal Use...................................................................................... 147

Chapter Seven: Implementing a good practice regulatory regime...................................... 149

7.1  Performance against identified enablers.................................................................... 150

7.1.1  Alignment with international requirements......................................................... 151

7.1.2  Timelines............................................................................................................... 151

7.1.3  Guidelines............................................................................................................. 151

7.1.4  Engagement and dialogue.................................................................................... 152

7.1.5  Tracking of applications........................................................................................ 152

7.1.6  Processes and procedures.................................................................................... 152

7.1.7  Publication............................................................................................................ 153

7.1.8  Internal resources................................................................................................. 153

7.2  Core attributes of good practice regulatory systems.................................................. 154

7.2.1  Data and analysis – post-market monitoring....................................................... 154

7.2.2  Appropriate legislative framework...................................................................... 161

7.2.3  Organisational structure and culture................................................................... 163

7.2.4  Future funding models.......................................................................................... 170

Appendix A: Submissions Received........................................................................................ 177

Appendix B: Consultations with Stakeholders........................................................................ 181

EXECUTIVE SUMMARY

The Independent Review of Medicines and Medical Devices Regulation commenced in October 2014. The Panel was engaged to assess the current regulatory framework and make recommendations on options to improve the way in which therapeutic goods are regulated in Australia. In undertaking the Review the panel has considered submissions and met with  a range of consumer, health professional, and industry stakeholders.

Mindful of the increasing globalisation of the pharmaceutical and medical devices industries and the rapid pace of innovation and change within the health care sector, the Panel has identified opportunities to enhance the regulatory frameworks for medicines and medical devices with a view to positioning the Australian National Regulatory Authority (NRA) for  the future. Continuing to harmonise the Australian regulatory system with international regulatory frameworks plays an important role in this regard. In identifying opportunities for reform, the Panel has been conscious of ensuring that there is no diminution of protections for the Australian public.

The Panel identified five core principles which underpinned the Review and provided a lens through which it could view the issues and options brought before it (Chapter One). We were also cognisant of the fact that the Review was only looking at one aspect of a complex regulatory system and that interface issues needed to be carefully managed, as a change at one point has the potential to impact other parts of the health system, such as subsidy programmes (Chapter Two).

Australia’s NRA for medicines and medical devices, the Therapeutic Goods Administration (TGA), has an excellent reputation both internationally and domestically for its work in ensuring the availability of high quality, safe, and efficacious therapeutic products on the Australian market. The TGA benchmarks well against comparable overseas NRAs in its regulation of medicines, however its performance in respect of devices is less notable. Retaining Australia’s regulatory capacity and decision making authority is critical (Chapter Three).

In undertaking the Review, the Panel has assessed the regulatory frameworks for medicines (Chapter Four) and medical devices (Chapter Five) to ascertain if they are fit-for-purpose  and whether processes are adequately streamlined and flexible. The Panel has also looked for opportunities to reduce duplication and inefficiencies. In doing so, it has made recommendations to:

·           expand the pathways by which sponsors can seek marketing approval for a medicine or medical device, including making provision for utilisation of assessments conducted by comparable overseas regulators, and for expedited assessments in defined circumstances;

·           identify comparable overseas NRAs using transparent criteria;

·           enhance post-market monitoring of medicines and medical devices and streamline post-market requirements in respect of products in the Australian Register of Therapeutic Goods; and

·           improve transparency and predictability of processes and decisions, to build trust and confidence in the NRA’s ability to ensure Australians have timely access to high quality, safe and efficacious products.

The Panel has also made recommendations to streamline access by consumers and health professionals to medicines and medical devices that have not been approved for use in Australia, in certain circumstances (Chapter Six).

Finally, the Panel has identified essential infrastructure to support the implementation of its recommendations (Chapter Seven), including an appropriate legislative framework; revised decision making and organisational structures; and mechanisms to support enhanced post- market monitoring of medicines and medical devices for safety and efficacy.

We invite you to examine the full set of recommendations in the following pages.

RECOMMENDATIONS

RECOMMENDATIONS RELATING TO THE NATIONAL REGULATORY AUTHORITY ROLE

Recommendation Six

The Panel recommends that in circumstances where a sponsor seeks registration of a new chemical entity in Australia via Pathway Two and has submitted all necessary materials, including an un-redacted evaluation report from a comparable overseas NRA, to the Australian NRA:

1.        The Australian NRA makes a recommendation regarding registration of the new chemical entity once it has satisfied itself that:

A.  The new chemical entity is identical in dosage form, strength, formulation and indications; and

B.  The new chemical entity will be manufactured at a plant that has received GMP certification from the Australian NRA (or from a comparable overseas NRA with whom the Australian NRA has co-recognition); and

C.  The manufacturing process to produce the new chemical entity will be identical to that assessed by the comparable overseas NRA for the overseas product; and

D.  There are no specific issues regarding applicability of the submitted data to the Australian context that need to be examined; and

E.   Proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements

2.        Where the new chemical entity seeking registration in Australia does not meet conditions 1A to 1D above, the Australian NRA undertakes an assessment of the extent to which the differences have the potential to impact the quality, safety or efficacy of the product.

A.  If the differences are assessed to have minimal impact on product quality, safety or efficacy, the Australian NRA should satisfy itself that the proposed product labelling, Product Information, and Consumer Medicine Information is appropriate and consistent with Australian requirements before making a recommendation regarding registration of the new chemical entity in the ARTG.

B.  Where differences between the new chemical entity seeking registration in Australia and that approved by the comparable overseas NRA have the potential to impact product quality, safety or efficacy, before making a recommendation regarding registration of the new chemical entity in the ARTG, the Australian NRA should:

I.                              Undertake an assessment of the application for registration to the extent necessary to satisfy itself that any potential impact of the differences on quality, safety or efficacy have been addressed and/or taken into consideration in assessing risk and benefit; and

II.                               Assess whether the proposed product labelling, Product Information, and Consumer Medicine Information are appropriate and consistent with Australian requirements.

Recommendation Seven

The Panel recommends that in circumstances where a sponsor seeks registration of a generic medicine or biosimilar in Australia via Pathway Two and has submitted all necessary materials, including an un-redacted evaluation report from a comparable overseas NRA, to the Australian NRA:

1.  The Australian NRA makes a recommendation regarding registration of the generic medicine or biosimilar once it has satisfied itself that:

A.        The generic medicine or biosimilar is identical in dosage form, strength, and formulation to the product approved by the comparable overseas NRA; and

B.        The generic medicine or biosimilar will be manufactured at a plant that has received GMP certification from the Australian NRA (or from a comparable overseas NRA with whom the Australian authority has co-recognition); and

C.        The manufacturing process to produce the generic medicine or biosimilar will be identical to that assessed by the comparable overseas NRA for the overseas product; and

D.        If the product is a generic medicine - the reference product used by the comparable overseas NRA when assessing bioequivalence was identical to, or interchangeable with, the Australian reference product; or

E.         If the product is a biosimilar - the overseas reference product and the Australian reference product were the same; and

F.         Proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

2.  Where the generic medicine seeking registration in Australia does not meet conditions 1A to 1D above, the Australian NRA undertakes an assessment of the extent to which the differences have the potential to impact the quality, safety or efficacy of the product.

A.        If the differences are assessed to have minimal impact on product quality, safety or efficacy, the Australian NRA should satisfy itself that the proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements before making a recommendation regarding registration of the generic medicine in the ARTG.

B.        Where differences between the generic medicine seeking registration in Australia and that approved by the comparable overseas NRA have the potential to impact product quality, safety or efficacy, before making a recommendation regarding registration of the generic medicine in the ARTG, the Australian NRA should:

I.                              Undertake an assessment of the application for registration to the extent necessary to satisfy itself that any potential impact of the differences on quality, safety or efficacy have been addressed; and

GLOSSARY OF ABBREVIATIONS

CHAPTER ONE: BACKGROUND TO THE REVIEW

On 24 October 2014 the then Minister for Health, the Hon Peter Dutton MP and the Assistant Minister for Health, Senator the Hon Fiona Nash, announced the establishment of an expert panel to undertake an independent Review of Medicines and Medical Devices Regulation (the Review). In announcing the Review, Minister Dutton noted that medical technology is constantly evolving and that a modern regulatory framework was required to ensure Australians can access the latest treatments in a timely manner. Senator Nash indicated the Review was a key step in efforts to remove ineffective regulation and encourage greater competition and innovation in the medicines and medical devices sectors and would complement the Government's Innovation and Competitiveness Agenda.

1.1     Objective of the Review

The objective of the Review is to make recommendations to assist the Government to enhance the regulatory framework for medicines and medical devices so that:

·           Australia continues to be well positioned to respond effectively to global trends in the development, manufacture, marketing and regulation of therapeutic goods.

·           Areas of unnecessary, duplicative or ineffective regulation are removed or streamlined without undermining the safety or quality of therapeutic goods available in Australia.

1.2     Terms of Reference

The Panel was asked to undertake the Review in accordance with the following Terms of Reference.

Background

1.  Australia has, by a number of different measures (life expectancy, survival with cardiovascular disease, survival with a range of cancers), amongst the best health outcomes of the OECD countries.

2.  The regulatory framework of the Therapeutic Goods Administration (TGA) provides an important protection to the Australian community ensuring only safe and effective medicines and medical devices are granted authority to be marketed and/or exported.

3.  The TGA also performs crucial post-market roles including the regulation of advertising for therapeutic products and the monitoring of adverse events to ensure the ongoing safety of therapeutic products.

4.  A safe and effective regulatory framework for medicines and medical devices should balance safety and market access priorities to the benefit of patients and industry and align with the government’s commitment to increase productivity and competitiveness.

5.  It is timely to review the regulatory framework and processes under which the TGA operates, to identify opportunities to improve its operations. This will ensure the TGA is able to operate effectively and efficiently in comparison with high quality international regulators, in respect of regulatory imposts such as timeframes and costs to industry, while also maintaining appropriate public health and safety protections.

Scope of the Review

6.  The Review will benchmark TGA regulatory arrangements against trusted international authorities.

7.  The Review will make recommendations and related implementation information to:

a.  Ensure there is an appropriate balance between risk and benefit in the regulation of prescription, over-the-counter, complementary medicines and medical devices, as well as access for individuals to unapproved medicines and medical devices;

b.  Simplify and streamline the approval processes undertaken by TGA. This will include recommendations on:

i.            fast tracking approvals processes for medicines and medical devices;

ii.            opportunities for working together with trusted regulators in other jurisdictions, including the potential for work-sharing assessments for products marketed in multiple countries; and

iii.            exploring how risk assessments, standards and determinations of trusted regulators can be used more extensively by Australian regulators when approving the supply of medicines and medical devices.

c.  Ensure regulatory arrangements are sufficiently flexible to accommodate developments in medicines and medical devices, including exploring opportunities to streamline approvals that cross regulatory categories;

d.  Improve the processes that assist industry, researchers and consumers to navigate the regulatory system for medicines and medical devices;

e.  Support work underway on medical device reforms and clinical trial approval arrangements in Australia; and

f.  Any other matters that the review committee regards as important and relevant to the safe and efficient supply of effective medicines and medical devices to the Australian people.

8.  The Review will not make recommendations in relation to:

a.  Any aspect of the Pharmaceutical Benefits Scheme;

b.  Work by the Department of Health on the reimbursement systems, including reimbursement and or subsidy of medicine and medical devices;

c.  National Health and Medical Research Council arrangements relating to research and development; or

d.  Work currently underway by the Department of Health and the Department of Industry on ethics processes for clinical trials.

9.  The Review report will be provided to the Minister for Health, copied to the Prime Minister, the Assistant Minister for Health, and the Parliamentary Secretary to the Prime Minister responsible for deregulation, by 31 March 2015.

1.2.1 Additional requirements

In addition to the Terms of Reference the Panel was asked to identify:

·           Opportunities for reducing red tape burden in the short and long term.

·           Strategies for ensuring red tape reduction can be sustained.

·           Issues threatening the achievement of reductions in regulatory burden.

1.3     Timeframe for the Review

The Panel is undertaking the Review in two stages:

Stage one – The first stage of the Review is the subject of this report and focuses on the regulation of prescription medicines, over-the-counter (OTC) medicines and medical devices.

Stage two – The second stage of the Review will focus on the regulatory framework for complementary medicines and for the advertising of therapeutic goods. While the Panel sought comment from stakeholders on the advertising of medicines and medical devices as part of stage one of the Review, it did not consider it appropriate to make  recommendations on this issue until it had also considered advertising in the context of complementary medicines. The Panel will provide its stage two report to the Government by mid-2015.

1.4     The Review Panel

1.5     Review Secretariat

The Review Panel has been supported by a small Secretariat located within the Best Practice Regulation and Deregulation Division, Australian Government Department of Health.

1.6     Review Methodology

In undertaking the Review the Panel was cognisant of the importance of understanding stakeholder views about the current regulatory framework for medicines and medical devices. In particular, what aspects of the regulatory process were working effectively and where was there room for improvement? The reporting timeframes for the Review were  not conducive to the Panel undertaking widespread consultation with stakeholders throughout the Review process. As such, in order to rapidly develop an understanding of what some of the key issues were from the perspective of different stakeholders, the Panel undertook an analysis of stakeholder submissions to previous reviews or consultations. As a

result of that analysis the Panel identified five key themes that highlighted the concerns previously raised by stakeholders about the regulatory framework for medicines and medical devices. These themes were:

1.        Duplication of regulatory processes, which was seen as creating unnecessary regulatory burden on industry and undermining timely access to new technologies.

2.        Lack of flexibility, which was seen as hindering early access to innovative products.

3.        Regulatory requirements were not considered to be commensurate with the risk posed by some regulated products.

4.        The regulatory framework was viewed as overly complex and not well understood by those who are required to interact with it.

5.        Some regulatory processes were considered to be overly burdensome and out of step with technology.

In addition to identifying these core themes, which assisted the Panel to summarise and categorise the concerns that had previously been expressed by stakeholders about the regulation of medicines and medical devices, the Panel identified five key principles which were considered appropriate to underpin the Review. These principles provided a lens through which the Panel could view the issues and options brought before it.

1.6.1  Principles underpinning the Review

1.6.2  Discussion papers

Having reviewed previous submissions and identified core principles to underpin the Review, the Panel developed two discussion papers that summarised its understanding of the issues and concerns held by stakeholders related to the regulation of medicines and medical devices by the TGA. The first discussion paper, released on 21 November 2014, addressed issues relating to the regulation of prescription and OTC medicines and medical devices. The subsequent discussion paper was released on 20 February 2015 and addressed issues relating to the regulation of complementary medicines.

The discussion papers summarised concerns that had been expressed by stakeholders in the past about the regulation of medicines (including complementary medicines) and medical devices, and some of the options put forward by stakeholders to address these concerns. The Panel included a series of key questions for consideration in each discussion paper as a means of encouraging stakeholders to explore each issue further. The intent was to promote a dialogue about the issues raised and assist the Panel form a view about whether stakeholders had a shared understanding of the issues and options for the future.

Both discussion papers were published on the Department of Health’s website and accompanied by a call for submissions inviting stakeholders to provide input to the Review. The call for submissions was also emailed to a broad range of consumer, industry and health professional peak bodies, as well as to organisations or individuals who had registered an interest in the  Review.  Submissions  responding  to  the  first  discussion  paper  closed  on 5 January 2015, although late submissions were still considered. The submission period for responses to the discussion paper on complementary medicines is ongoing at the time of this report.

1.6.3  Submissions

In response to the Review of Medicines and Medical Devices Regulation Discussion Paper, the Panel received 103 formal submissions from a range of stakeholders (see Appendix A). As outlined in Figure 1 below, submissions were received from:

·           industry, including submissions from both individual companies and peak bodies representing the interests of industry;

·           health professionals, including both individuals and representative bodies;

·           consumer peak bodies and individual consumers;

·           academics;

·           members of a number of expert advisory committees, including the Advisory Committee on Prescription Medicines; and

·           other groups, such as private health insurers and regulatory advice services.

Figure 1: Submissions received in response to the Panel’s discussion paper on Medicines and Medical Devices Regulation

Where consent was provided by the author, submissions received were published on the Department of Health’s website.

The Panel reviewed all submissions. Where submissions raised issues that the Panel wished to further explore or clarify, the Panel sought a meeting with the relevant party. Where possible, all Panel members were present at such meetings, but on occasion meetings were held with the Chair only, or with two members of the Panel.

1.6.4  Consultations

As noted above, the Panel met with a range of stakeholders to discuss their submissions or seek clarification on issues raised. A list of organisations external to the Department of Health with whom the Panel consulted is at Appendix B. Throughout the Review, the Panel also regularly sought information and advice from the TGA or from other relevant officers within the Department of Health.

In addition, the Panel:

·           Held a forum in Sydney on Wednesday 12 November 2014 to brief peak consumer, industry and health professional bodies on the terms of reference for the Review and the approach that the Panel planned to take in terms of consultations.

·           Attended a meeting of Cancer Australia’s Intercollegiate Advisory Group on Thursday    5 February 2015. The Advisory Group has membership from relevant medical specialties, public health organisations, and consumer groups with an interest in the prevention and treatment of cancer.

·           Met with a number of public health organisations and consumer groups in Sydney on Friday 13 February 2015 and Melbourne on Thursday 19 February 2015.

·           Held a teleconference on Thursday 19 February 2015 with representatives from the Consumers Health Forum of Australia and a number of state and territory peak bodies representing the interests of consumers.

CHAPTER TWO: OVERVIEW

As outlined in its terms of reference, the Panel was asked by the Australian Government to undertake a review of those aspects of medicines and medical devices regulation that are currently administered by the Therapeutic Goods Administration (Therapeutic Goods Regulation). In broad terms, this includes: pre-market assessment of medicines and medical devices for safety, quality and efficacy: post-market monitoring to identify emerging issues and ensure compliance with regulatory requirements relating to, for example, manufacturing practice and promotion; and the oversight of schemes designed to provide consumers access to unapproved products in defined circumstances. These regulatory activities are, however, only one aspect of the regulation of medicines and medical devices. Therapeutic Goods Regulation does not exist in a vacuum in Australia – it is part of a number of interrelated initiatives and strategies that occur across the health system and across levels of government, aimed at achieving broader government objectives related to safety and quality; access and equity; affordability and sustainability; and industry viability and competitiveness, as outlined in the National Medicines Policy.¹

As demonstrated in Figure 2, the Australian health care system is complex, with a myriad of interconnected parts. The regulation of medicines and medical devices occurs across all aspects of the system – through, for example, Australian government regulation of clinical trials and subsidy programmes; or State and Territory Government regulation of the manufacture, distribution, storage and use of medicines under poisons legislations; or management of device procurement and storage under asset management frameworks for medical equipment.ⁱ

There are also interface issues with regulatory regimes for other products, such as food, chemicals and consumer goods. The demarcation line that differentiates a therapeutic good from: a food (regulated by state and territory food authorities); or a chemical (regulated by the National Industrial Chemicals Notification and Assessment Scheme); or a general consumer good (regulated by the Australian Competition and Consumer Commission) is often blurred, adding complexity for industry, consumers and regulators. It also leads to very similar products being subjected to quite diverse regulatory regimes. This issue is discussed further in Chapters Four and Five.

In undertaking the Review the Panel was cognisant of the fact that it was looking at one small part of a complex regulatory system. As with any system, change at one point has the potential to impact on the system as a whole, as well as on its component parts. These impacts may be unpredictable - unforeseen or perverse outcomes are always a risk of reform.

i See for example, State Government of Victoria, Medical Equipment Asset Management Framework FAQ webpage. Accessed on 4 March 2015 at http://www.health.vic.gov.au/archive/archive2011/med- equip/faq.htm

Figure 2: Australian health system structure and funding flows*

Where the Panel has identified possible flow-on effects to other parts of the system it has attempted to alert the reader to these. The Panel trusts that the Australian Government will consider how best to mitigate (or exacerbate as the case may be) these flow-on effects in implementing any reforms to the regulatory frameworks for medicines and medical devices.

In addition, Australia is part of a global community, and harmonisation of regulatory practices and the adoption of common processes are being developed with therapeutic goods regulators internationally. Where regulators in different jurisdictions can agree common standards, guidelines and regulatory requirements, the time to market for therapeutic products can be shortened. Better alignment of regulatory requirements directly benefits industry and consumers. From an industry perspective, harmonisation of requirements between regulators can reduce the time taken to develop new medicines and devices, lead to less cumbersome approval processes between countries (including reduced cost and time in preparing different dossiers for different markets) and increase the speed to market, all of which are important to industry.² From a consumer perspective, harmonisation provides more timely access to innovative therapies and may reduce their cost (as costs incurred to achieve market approval are factored into the subsequent price of the medicine or medical device, and increased competition will ultimately reduce prices).

Opportunities to enhance the alignment of Australia’s regulatory frameworks for medicines and medical devices with international regulatory practice are discussed throughout this report. In particular, the Panel has considered the Government’s policy position that, where a product has been approved under a trusted international risk assessment, Australian regulators should not impose any additional requirements unless there is good reason to do so (discussed in Chapters Three, Four and Five). Regulation, in all its forms, is an important mechanism for governments to achieve strategic policy objectives for the benefit of the community, particularly where the health and safety of Australians is concerned. Good regulation begins with clarity about the problem or risk that needs to be managed and provides for flexibility in how this occurs. As such, in considering these issues the Panel was mindful to ensure that regulatory alignment does not stifle opportunities for regulatory innovation.

A further context for the Review is the Australian Government’s desire to promote better regulation, by reducing or eliminating unnecessary, ineffective or inefficient rules or requirements. In the context of the regulation of medicines and medical devices, this does not mean removing requirements that play an important role in protecting Australians from unsafe medicines and medical devices. Rather, it is about questioning why Australia regulates medicines and medical devices in the way it does. What problems are regulatory rules and procedures trying to solve, and how effectively and efficiently do they do this? Does the Australian regulator duplicate the efforts of other Australian or overseas organisations and, if so, does this result in enhanced protections for the Australian community, or does it just slow access by Australian consumers to innovative technologies?

Are there opportunities to enhance community protections and reduce inefficient or ineffective regulations?

A critical aspect of the Review has therefore been to examine whether the regulatory frameworks for medicines and medical devices are fit for purpose. These frameworks have been in place for around 25 years and 13 years respectively, so such an examination is timely. In undertaking this examination, the Panel has considered matters such as whether there is an appropriate balance between risk and benefit, and whether processes are adequately streamlined and flexible. The Panel has also reflected on the broader principles of best practice regulation and the extent to which the regulatory frameworks for medicines and medical devices meet these principles. For example, the Panel has considered whether:

·           policy objectives of the regulatory frameworks for medicines and medical devices are clear and whether the regulation is achieving its policy objectives in a manner that minimises the cost for government, business and the community;

·           regulatory requirements are transparent and well-defined;

·           regulatory effort is appropriately matched to the risk posed by the regulated products or processes;

·           the regulatory frameworks strike an appropriate balance between principles of outcomes-based regulation and prescriptive regulation;

·           the regulatory frameworks include any examples of inconsistencies, overlapping regulation, redundancies, excessive regulatory coverage or excessive reporting or recording requirements; and

·           there are transparent and consistent procedures for making decisions under the legislation.

The regulatory frameworks for medicines and medical devices are discussed in Chapters Four and Five respectively, while Chapter Six addresses access to unapproved medicines and medical devices. Given the complexity of the regulatory frameworks and the timeframe for the Review, the Panel has, by necessity, only been able to undertake this assessment at the highest level. Further analysis would form an important part of any reform process.

The Panel is cognisant of the fact that the success of any regulation in achieving Government's objectives depends not just on what the law provides, but also on how the law is interpreted and administered. According to the Centre for Innovation in Regulatory Science, while ‘regulatory systems vary across countries as well as over time … the characteristics that reflect the activities of a well-developed regulatory agency are recognised through four attributes that are embedded into their process and procedures.’³ These enablers are addressed in Chapter Seven and include:

·           Transparency – For example, having detailed guidelines and published timeframes, the capacity for sponsors to track the status of applications, and the publication  of materials summarising the basis for approvals.

·           Timeliness – This includes having defined processes, procedures and project management, and adhering to target timeframes for decision making.

·           Predictability – This includes, for example, the usefulness of published guidelines, dialogue between the regulator and the regulated, and alignment with international requirements.

·           Quality – This relates to the competency of staff, the role of experts, the scientific basis for decision making and the scientific and legal consistency of decisions.⁴

Each of these enablers is achieved not by the way in which legislative frameworks are drafted, although that may assist, but rather by how the regulatory authority goes about its work – how it builds the capacity of staff; how it communicates with applicants and sponsors; and how it relates to, and communicates with, the broader community.

Finally, in undertaking this Review, the Panel has been mindful of the regulatory pendulum. That is, the experience in both Australia and internationally, is that the community and governments respond to a negative event or crisis by looking to more stringent regulatory controls as a means of preventing a recurrence of the event. Over time, as things go along smoothly, governments will generally look to loosen the regulatory reins on industry so as to boost competitiveness and productivity. Thus the regulatory pendulum swings back and forth in response to the prevailing conditions. This cycle is a major risk to sustainable regulatory reform. As such, in considering opportunities to reduce regulatory burden, the Panel has taken a conservative approach, developing options for reform that it believes  have the capacity to both reduce duplicative, ineffective, or inefficient regulation and enhance consumer protections.

1 Department of Health and Ageing (1999), National Medicines Policy, Commonwealth of Australia, pp. 2-3. 2 Weisfeld V. & Lustig T.A. (editors) (2013, October 24), Forum on Drug Discovery, Development, and Translation; Board on Health Sciences Policy; Institute of Medicine (IOM). International Regulatory

Harmonization Amid Globalization of Drug Development: Workshop Summary. National Academies Press (US), Washington (DC). Available at: http://www.ncbi.nlm.nih.gov/books/NBK174222/

3 Centre for Innovation and Regulatory Science (2011), Emerging Markets focus study - Understanding the enablers of good regulatory process and decision making. What are the features that enable a transparent, timely, predictable and good-quality review? Accessed online on 3 March 2015 at: http://cirsci.org/content/november-2011-slide-month

4 Ibid.

14

CHAPTER THREE: INTRODUCTION

The regulation of medicines and medical devices in Australia plays a critical role in protecting the health and safety of the Australian community. Medicines and medical devices have saved the lives of numerous Australians and have contributed to improved quality of life for many more. But few products are completely safe in all circumstances and use of these products, even as intended, is not without risk.

According to the World Health Organization (WHO):

The use of ineffective, poor quality, harmful medicines can result in therapeutic failure, exacerbation of disease, resistance to medicines and sometimes death. It also undermines confidence in health systems, health professionals, pharmaceutical manufacturers and distributors. Money spent on ineffective, unsafe and poor quality medicines is wasted – whether by consumers or governments. Governments need to establish strong national regulatory authorities (NRAs), to ensure that the manufacture, trade and use of medicines are regulated effectively, to protect and promote public health.¹

Australian health care consumers and the broader community have a reasonable expectation that medicines and medical devices available on the Australian market will be of high quality, safe to use, and efficacious. Regulation is essential as the potential for serious harm to consumers from medicines and medical devices

is high and there is an information asymmetry between those who manufacture or sell medicines and medical devices and those who consume them. That is, health care consumers do not generally have the necessary knowledge and skills to make decisions about the safety, quality, risks and benefits associated with a medicine or medical device themselves. Instead they rely on Government health authorities, together with their clinician, to make this assessment on their behalf. In addition, Australian governments subsidise other

Governments need to

establish strong national regulatory authorities to ensure that the manufacture, trade and use of medicines are regulated effectively.

WHO

aspects of the health system and would therefore incur much of the cost associated with the use of poor quality, ineffective or unsafe medicines and medical devices.

It is, therefore, in the interests of both governments and the community to regulate medicines and medical devices, and to do so effectively and efficiently.

3.1     National Regulatory Authority

The authority responsible for regulating therapeutic goods in Australia is the Therapeutic Goods Administration (TGA), which is part of the Australian Government Department of Health. Throughout this report, when discussing past actions of the authority, the Panel has referred to the TGA. However, to be consistent with the nomenclature used by the World Health Organization, when referring to the Australian regulatory authority in general terms or in future tense, the Panel has used the term ‘National Regulatory Authority’ (NRA).

The NRA is responsible for regulating a diverse range of therapeutic products, including prescription medicines, vaccines, sunscreens, vitamins and minerals, medical devices, blood and blood products.ⁱ The regulatory framework under which the NRA works is set out in the Therapeutic Goods Act 1989 (the Act) and related Regulations.

The national system for regulating therapeutic goods focuses on the quality, safety, efficacy and timely availability of therapeutic goods that are used in, or exported from, Australia. Regulatory decisions made by NRA staff are generally made under delegations from the Secretary or Minister. The NRA maintains this system by applying scientific and clinical expertise to assessing the evidence of risks and benefits of use of therapeutic goods. This involves:

·           Undertaking assessments of new therapeutic goods before they are released to the market (pre-market).

•     Higher risk (prescription and over-the-counter (OTC)) medicines are ‘registered’ in the Australian Register of Therapeutic Goods (ARTG) and evaluated for quality, safety and efficacy prior to approval.

•     Lower risk medicines (such as complementary medicines) are ‘listed’ in the ARTG and must only contain pre-approved, low-risk ingredients. These goods are not independently assessed for quality, safety or efficacy prior to listing.

•     Devices and biologicals are included in the ARTG and are evaluated for quality, safety and performance based on their risk level. For medical devices, this assessment may be undertaken by the manufacturer (self-assessment), an overseas conformity body, and/or by the TGA, depending on the risk level of the device.

·           Ongoing monitoring of products already on the market with a view to identifying safety risks and breaches of compliance with regulatory requirements in relation to these products (post-market).

·           Assessing the suitability of medicines and medical devices for export.

·           Inspecting and licensing manufacturing sites in Australia and assessing the standard of overseas manufacturing sites.

i Note: The regulation of blood and blood products is not included in the terms of reference for this Review.

·           Providing communication and education programmes and partnership activities tailored to consumers, health professionals and industry.

Figure 3 provides an overview of the processes used by the TGA in regulating medicines and medical devices in Australia.

Figure 3: Overview of TGA Regulatory Processes

Source: Therapeutic Goods Administration, Half-yearly performance reports: January to June 2014.²

3.1.1  Australian Register of Therapeutic Goods (ARTG)

As at 30 June 2014 there were 78,316 therapeutic products included in the ARTG. Approximately 57 per cent of these products were medical devices (including other therapeutic goods and export only medical devices); 22 per cent were prescription or OTC medicines; and 15 per cent were listed medicines, primarily complementary medicines. The remaining 5-6 per cent of entries related to biologicals, registered complementary medicines, export only medicines or in-vitro diagnostic devices (IVDs).

3.1.2  Funding

The TGA is required by government to fully recover the operating costs for all activities that fall within the scope of the Act, including its public health responsibilities, such as communication and education, through the imposition of fees and charges on industry. Fees predominantly cover the costs of pre-market activities, such as the evaluation of data dossiers for the registration of medicines or inclusion of medical devices in the ARTG.

Charges predominately cover the costs of post-market activities such as pharmacovigilance and product recalls, and are applied annually for products included in the ARTG.

A large number of TGA activities are not able to be explicitly cost-recovered. These include activities such as: administrative governance requirements; participation in international collaborative forums; the Special Access and Authorised Prescriber Schemes, which provide access to unapproved medicines; a fee waiver for ‘Orphan’ drugs; cost of reviews of regulatory decisions provided for under section 60 of the Act; and the cost of legal challenges. These costs can vary between $10 million and $20 million per annum and must be factored into overall fees and charges.

The list of fees and charges can be found in the Therapeutic Goods (Charges) Regulations 1990 and are reviewed annually. In 2013-14, TGA revenue was approximately $132 million and it had expenses totalling around $133 million.³

3.1.3  TGA performance

The TGA is widely respected internationally and domestically as a regulator of therapeutic goods. In submissions to the Review many stakeholders, across industry, health professional and consumer groups, emphasised the high quality of the assessments undertaken by the TGA, particularly in the medicines space. Nevertheless, the TGA has been subject to criticism about the time it takes to approve medicines and medical devices. A number of  stakeholders have asserted that the TGA is slower than its overseas counterparts in providing pre-market approval for medicines and medical devices and have questioned the need for independent evaluation by the TGA of medicines and medical devices that have already been approved by overseas regulators, such as the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). They argue that to do so is duplication of effort, which only serves to delay access by Australians to innovative medicines and medical devices.

Indeed, in 2014 the Australian Government adopted the principle that:

….if a system, service or product has been approved under a trusted international standard or risk assessment, Australian regulators should not impose any additional requirements unless it can be demonstrated that there is a good reason to do so. All Commonwealth Government regulatory standards and risk assessment processes will be reviewed against this principle.⁴

Noting this principle, and concerns from some stakeholders about the timeliness of TGA assessments of medicines and medical devices, the Panel considered a number of questions:

1.        Is there evidence to support assertions that pre-market assessments by the TGA are less timely than those conducted by comparable overseas NRAs?

2.        Would greater use of assessments by ‘trusted’ overseas regulators lead to more timely market access to innovative products by Australian consumers?

3.        Would greater use of assessments by ‘trusted’ overseas regulators reduce duplication and cost to industry?

As the nature of the pre-market assessment process is different for medicines and medical devices, the Panel considered these issues in turn for each type of product.

3.2     Medicines

3.2.1  Timeliness of approvals

In respect of the approval of medicines, the Panel examined data produced by the Centre for Innovation in Regulatory Science (CIRS), which benchmarks the performance of major regulators internationally. In its R&D Briefing 55, CIRS analysed the approval of new active substances across six NRAs between 2004 and 2013.⁵ The NRAs were the FDA, the EMA, Health Canada, Swissmedic, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and the TGA.

The CIRS analysis found that the past decade has seen major improvements in median approval times across all six regulators and there has been a convergence of approval timeframes when compared to the beginning of the decade (see Figure 4). That is, the difference in the median approval time between the fastest and slowest agency has decreased from approximately 500 days in 2004 to 200 days in 2013.⁶ As such, while the TGA’s median approval times have improved markedly over the past decade, particularly following implementation of revised procedures in 2010, overseas regulators have also enjoyed similar improvements. Thus, the data demonstrates that the TGA approves new substances faster than some comparable overseas regulators but slower than others.

Figure 4: New Active Substance median approval time for six NRAs 2004-2013*

*Based on a graph produced by the Centre for Innovation in Regulatory Science.7

This is further demonstrated by an analysis of median approval timeframes for new active substances in 2013 (refer Table 1), which indicates that Swissmedic’s median approval timeframe is the slowest, at 511 days, while the FDA is the fastest, with a median approval time of 304 days. The TGA ranks in the middle with a median approval time of 391 days, 87 days slower than the FDA, but 87 days faster than the other large regulator, the EMA.

Table 1: Approval of New Active Substances 2013*

*Table collated from data from the Centre for Innovation in Regulatory Science.⁸

It is important to note, however, that median approval times for new active substances outlined in Table 1 reflect approvals of these substances under both expedited and routine approval pathways. Expedited approvals occurred in all jurisdictions except Australia, as the Act does not provide for the TGA to offer an expedited approval pathway. Expedited approvals comprised between 10 and 39 per cent of all approvals in the five overseas NRAs. Approval times for new active substances assessed via expedited pathways were between 123 and 318 days less than approval times for new active substances assessed through routine approval pathways. If expedited approvals are removed from the data (refer to Table 2), the TGA remains in the middle in terms of median approval times, but the gap between it and Health Canada, which has the fastest median approval time, reduces to 36 days.

Table 2: Approval of New Active Substances via routine approval pathways 2013*

*Table collated from data from the Centre for Innovation in Regulatory Science.⁹

Based on this analysis, the TGA appears to be performing reasonably well, with a median approval time for new active substances that is around five weeks slower than that achieved

by its most efficient overseas counterpart, Health Canada. Why then the continued perception that the TGA is slow to register new substances?

Availability of a new medicine on the Australian market is determined by both the time that it takes a sponsor to submit a data dossier to the TGA seeking registration, and the time that it takes the TGA to undertake an assessment of the medicine for safety, quality and efficacy. An analysis by the CIRS¹⁰ of the roll out to world markets of new active substances that were launched between 2005 and 2010 (n=146) demonstrates there can be long delays between a company first submitting a data dossier to an overseas regulator and subsequently submitting it to the TGA (or to other medium sized regulators such as Health Canada or Swissmedic). This is particularly the case for small to medium sized companies, who took nearly twice the time to roll out their products internationally when compared to top companies (defined as those with a research and development spend of greater than

$US 3 billion in 2010).¹¹

This ‘submission gap’ contributes to the time it takes for new medicines to become available on the Australian market when compared to overseas markets (such as the US and Europe) whose regulators tend to be the first point of

submission of data dossiers by both small and large companies. For example, the CIRS analysis identified median submission gaps of between 34 and 467 days for 78 products that were subsequently registered by the TGA, which included anti-cancer medicines (148 day median submission gap); cardiovascular medicines (231 day median submission gap) and nervous system medicines (467 day median submission gap). As at 31 December 2012, only 53 per cent of the

Availability of a new medicine

in Australia is determined by both the time that it takes a sponsor to submit a data dossier and the time that it takes the TGA to undertake an assessment of the medicine for safety, quality and efficacy.

medicines launched internationally between 2005 and 2010 were approved for use in Australia, compared to 72 per cent in the US.

These submission gaps may be contributing to a perception that the TGA is slow to approve new drugs for market, as observers will not necessarily be aware the dossier was not submitted in Australia at the same time as it was submitted in, for example, the US. To the observer it will simply appear that a potentially life-saving or life-changing drug is available to patients in the US but not in Australia, as it has not yet been approved by the regulator. This concern may be further exacerbated if the overseas regulator considers the medicine through an expedited approval pathway, which will result in the product being made available in a much shorter timeframe than it can be approved in Australia, which does not have capacity under the current legislative framework to offer expedited approval.

Having analysed the available data, the Panel is of the view that the TGA does have due regard to timeliness when assessing new medicines for the Australian market. Once it

receives an application for the registration of a new active substance in the ARTG, the TGA outperforms the EMA and a number of medium sized regulators in terms of its median approval time and it is only marginally slower (by around five weeks) than Canada, the best performing regulator. That is not to say, however, that there is not room for improvement. As discussed later in this report, it is the Panel’s view that increased use of online systems for interacting with sponsors; introduction of expedited approval pathways; and greater engagement of the Australian regulator with pharmaceutical manufacturers and sponsors throughout the lifecycle of a medicine, including prior to the submission of data dossiers for approval; all have the capacity to enhance approval timeframes.

3.2.1.1  Predictability

While timeliness of approvals is important, another common efficiency measure is the predictability of the review process. In particular, adherence by the NRA to its own timing and procedural measures is important to industry, as it allows them to better plan for the release of a product onto the market. In its recent R&D Briefing 55, the CIRS noted the six NRAs it examined had all decreased the variability in their approval timeframes over the past decade (thereby increasing predictability). It further noted that the:

EMA and the TGA had the least variability in approval times over the past decade, and have established even more consistency in review timing in the last five years.¹²

According to the TGA’s key performance indicators report for the period July to December 2014, 100 per cent of new applications were processed within the statutory timeframe of 255 working days.

Thus, in terms of predictability of approval times, the TGA, along with the EMA, is setting  the benchmark for other NRAs.

3.2.2  Would use of overseas assessment reports improve timeliness?

The data from the CIRS study suggests that, historically, pharmaceutical companies submit data dossiers for the registration of a new medicine to regulators at different times. But the Panel received anecdotal advice from both industry stakeholders and the TGA that this is changing, and that simultaneous submission of dossiers to multiple regulators is becoming more common. The degree to which use of overseas assessment reports may result in more timely availability of new medicines on the Australian market is, to some extent, dependent on which of these trends continues or, alternatively, on whether sponsors change their submission strategy for the Australian market in response to the availability of a streamlined option to utilise overseas assessments.

The following examples use:

·           the average 2013 median approval times for non-expedited approval of new active substances for the six overseas regulators from the CIRS study into the impact of the changing regulatory environment on the approval of new medicines;¹³ and

·           the median ‘submission gap’ for Australia from the CIRS study into the availability of new medicines.¹⁴

Simultaneous Submissions

If sponsors submit applications for their new medicines to all jurisdictions simultaneously, then use of overseas assessment reports is likely to slow the availability of new medicines in Australia. As illustrated in Figure 5, Australia’s median approval time in 2013 was only 36 days slower than its most efficient overseas counterpart, Canada. If the Canadian approval was to be used to support approval of the medicine in Australia, then the sponsor would need to submit an application to the Australian regulator, and the regulator would have to do any necessary assessment, within 36 days after the Canadian approval was granted in order to facilitate earlier availability. This is extremely unlikely.

Figure 5: Simultaneous lodgement of applications for marketing approval

Staggered Applications

If pharmaceutical companies were to continue to stagger the submission of their data dossiers to different regulators, then use of overseas assessment reports by the Australian regulator may result in a marginal improvement in the timeframe by which new medicines become available in Australia. That is, in the CIRS study the median submission gap between the FDA and the TGA was 181 days. This, combined with median approval times (based on 2013 data), means that a new medicine would be approved in the US 208 days before it was approved in Australia. If an assessment report from the FDA was to be used to support approval of a medicine in Australia, then theoretically it may facilitate quicker access to the medicine on the Australian market (see Figure 6).

Figure 6: Staggered lodgement of applications for marketing approval

The extent of any improvement in timeliness would depend on:

1.   The size of the submission gap. While the CIRS report identifies a median submission gap between lodgement of a submission in the US and its lodgement in Australia of 181 days, the submission gap varied by therapeutic area and company size. The median submission gap for ‘top’ companies was 132 days and for ‘non-top’ companies it was 441 days. The median submission gap for different therapeutic types ranged from 34 days for blood and blood forming organs to 467 days for nervous system therapies.¹⁵

2.   The time taken by the overseas regulator to approve the new medicine. If the approval times are above the median, then it will cut into any time benefit that might accrue from the Australian regulator utilising an overseas assessment report. The inverse is also true, for example, if an expedited approval pathway is used by the overseas regulator.¹⁶

3.   The time it would take the Australian regulator to do any necessary assessment. The Panel is of the view that some additional assessment by the Australian regulator is both necessary and appropriate. This is discussed in some detail later in this report.

Impact on Sponsor’s Submission Strategies

If the Australian NRA was to accept an overseas assessment report as the basis for registration of a medicine in the ARTG, this may impact the way in which sponsors view and interact with the Australian market place. For example, it may make the Australian market more appealing as it would reduce both the cost and time involved in having a new medicine included in the ARTG. However, it may also result in sponsors delaying their application for registration while they await the outcome of an overseas assessment.

The Panel notes that the current Therapeutic Goods Act and Regulations define two pathways to registration in the ARTG, known as ‘Category 1’ and ‘Category 2’, respectively.

The Category 2 pathway is open to medicines which have been approved in two other acceptable countries and, with a legislative maximum timeframe for determination of 175 working days (compared to 255 working days for Category 1 applications), offers accelerated market entry compared to the Category 1 pathway. Eligibility for the Category 2 pathway is restricted to medicines that have been approved in two other acceptable countries; which have the same formulation, directions for use and indications as approved in those two countries; and for which two independent evaluation reports are available.

Since its introduction in 1992, the Category 2 option has only rarely been used by applicants as a pathway for approval of new medicines. Reasons why this option has not been used more often may include the strict inclusion criteria; the difficulty in the applicant accessing full un-redacted copies of evaluation reports from other regulators (particularly the FDA); and the relatively small number of acceptable overseas regulators currently specified in the Regulations, comprising the FDA, Health Canada, UK’s Medicines and Healthcare Products Regulatory Agency (MHRA), Sweden’s Medical Products Agency and the Dutch Medicines Evaluation Board. The latter problem is accentuated because over the last decade or so, with the establishment and consolidation of the EMA, the three European regulators undertake relatively few evaluations of new medicines. Taken together, these constraints make the current opportunities for industry sponsors to access the Category 2 route extremely limited. As such, it would be important to ensure that any revised ‘Category 2’ pathway provided easier access for sponsors who may wish to use it.

Market Access vs Consumer Access

Market access is achieved by the inclusion of a product in the ARTG. But market access does not necessarily translate into consumer access because in practice the cost of the medicine may be prohibitively expensive acting as a barrier to access for most consumers. For example, in December 2014, the Australian media reported that a new medicine for the treatment of non-small-cell lung cancer would cost patients around $90,000 per annum if it were not subsidised.¹⁷

There is therefore, a further step in providing consumer access to medicines in Australia which involves consideration by the Australian Government about whether or not the medicine should be subsidised. This involves a sponsor, usually the drug company, making application to the Pharmaceutical Benefits Advisory Committee (PBAC) for listing of the medicine on the Pharmaceutical Benefits Scheme (PBS). The PBAC assesses the evidence on the drug's effectiveness, including its cost-effectiveness, compared to other medicines/treatments already available for the treatment of the proposed indication, and makes recommendations to the Australian Government about whether or not the medicine should be subsidised.

Timely access by Australian consumers to new medicines is, therefore, dependent on timely decisions about both product registration and subsidy. To facilitate this, the TGA and the

PBAC currently have parallel processes, whereby a submission to the PBAC may be lodged at any time from the date of lodgement of a TGA registration dossier. It will be important to ensure that any revised approval pathway for medicines which provides for the use of an overseas assessment report does not remove this capacity for parallel processing of applications by the TGA and PBAC.

Given the above, the Panel concluded that it is possible that use of overseas assessment reports may improve the timeliness of access by Australian consumers to innovative medicines.

3.2.3  Would use of overseas assessment reports reduce duplication?

As noted previously, for medicines to be supplied and marketed in Australia they must be included in the ARTG. For all but the lowest risk medicines, the TGA conducts a detailed evaluation of the product for safety, quality and efficacy, in order to determine if, on balance, the benefits of taking the medication outweigh the risks. The TGA undertakes this detailed evaluation irrespective of whether the medicine has already been assessed under  ‘a trusted international standard or risk assessment’, such as that conducted by the EMA or the FDA. This necessitates the sponsor of the medicine submitting a comprehensive data dossier and addressing any queries from the TGA, thus duplicating their effort in getting the product approved in other key markets. The sponsor must also pay a fee to the TGA. As at   1 July 2014 a sponsor seeking registration of a ‘new chemical entity’ is required to pay an application fee of $44,200 and an evaluation fee of $177,200.

Advocates for greater use of overseas assessment reports argue that very few drugs that are approved by one major regulator are subsequently rejected by another. As such, they assert that once a medicine has been approved by a ‘trusted’ overseas regulator, the TGA assessment is superfluous and imposes an unnecessary regulatory and cost burden on industry.

Use by the Australian NRA of assessment reports from ‘trusted’ overseas regulators would be expected to reduce regulatory burden and costs to sponsors in a number of ways.

1.         A reduction in registration fees, as under the Australian Government cost  recovery policy such fees are to reflect the efficient unit costs of delivering the specific good or service.¹⁸ As such, if use of an overseas assessment report reduced the time and resources that the Australian NRA needed to commit to the evaluation process, then this would be reflected in the registration fee.

2.         Remove the necessity to develop and submit a complete data dossier that is unique to Australia. The Common Technical Document (CTD) is a set of specifications for a dossier for the registration of medicines which is utilised by many regulators internationally. The CTD was developed by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and adopted by

the TGA in 2004. The CTD is a harmonised format for applications for registration of new chemical entities, however, actual content requirements may still differ between countries that have adopted the CTD. The CTD is divided into five modules. Module 1 includes administrative information and prescribing information specific to the country in which the application is being lodged. Modules 3 to 5 address quality, safety (non- clinical study reports), and efficacy (clinical study reports) respectively, while Module 2 provides a summary of Modules 3 to 5.

Reliance on an overseas assessment report would mean reliance on the CTD Modules     2 to 5 as submitted by the sponsor to the overseas regulator. The sponsor would, therefore, not have to modify these modules for submission to the Australian NRA. Preparation of a Module 1 that is unique to Australia would, however, still be required.

3.         Remove the necessity to respond to as many questions and requests for information from the Australian NRA as would be expected to occur if the Australian NRA were undertaking a de novo assessment. Responding to questions and data requests, while a necessary part of the evaluation process, can be both time consuming and resource intensive for sponsors. Indeed, one of the reasons the CIRS identified that ‘top’ pharmaceutical companies (i.e. those with 2010 R&D budgets >$US 3 billion) were able to internationalise their medicines quicker than smaller companies was that they ‘are more likely to have the resources to undertake the submission of dossiers and to support their review in multiple jurisdictions.’¹⁹

In addition, where use of an overseas assessment report results in a reduced time to market (and subsidy), this would be of considerable benefit to the sponsor. However, the inverse is also true. That is, should a sponsor choose to delay applying for registration of a medicine in the ARTG until an overseas assessment report is available, and this in turn delays obtaining listing of the medicine on the PBS, then this could result in lost profits.

3.3     Medical Devices

The term ‘medical device’ covers a vast array of products and equipment. A medical device can be a simple, low-risk product such as a tongue depressor or band aid. It can be an implantable device such as a joint replacement, a heart valve, or a coronary artery stent, or it can be a complex piece of equipment, such as a haemodialysis machine. As a result the risk profiles of different medical devices vary significantly. Class I devices generally have risk profiles akin to many consumer goods, while implantable devices have a much higher risk profile. Failure of such devices can result in serious diminution of a person’s quality of life, necessitate surgical intervention, and may even result in death.

Medical devices and the devices industry differ from medicines and the medicines industry in a number of ways. According to the Pan American Health Organization:

…many devices have a considerably shorter useful life than drugs given the high degree of innovation and constant turnover due to technological obsolescence. Unlike the drug industry, which (other than biotechnology) remains relatively static, the device industry is a dynamic one, with a diversity of products that is unparalleled in comparison to the field of pharmaceuticals. In turn, this diversity leads to spirited entrepreneurialism, particularly among small businesses. Thus the composition of the drug industry vis-à-vis the device industry is vastly different. Because the make- up of the device industry is far more heterogeneous, with a large proportion of small companies, special challenges face those tasked with regulating these products.²⁰

The shorter lifecycle of many medical devices and the nature of the industry means it is particularly important for regulatory processes to be timely, simple to navigate, and efficient, if consumers are going to gain access to technology before it becomes obsolete. Submissions to the Review from the medical device industry were, like the industry itself, heterogeneous, but there was a level of concern expressed about the timeliness of evaluations of medical devices by the TGA.

Benchmarking the performance of the TGA against other overseas NRAs with responsibility for the regulation of medical devices is much more difficult than with medicines, however. There is a high level of consistency in the way major NRAs conduct pre-market assessments of medicines, which provides some confidence in the validity of benchmarking data. Regulatory systems for medical devices are less developed²¹ and there is no standard approach internationally to pre-market assessment. The assessment that is undertaken by individual NRAs also differs according to the class or risk profile of the medical device. Thus in trying to undertake benchmarking, the Panel found it difficult to assure itself that the available data was comparing like with like. The following data should be read with these caveats in mind.

3.3.1  Timeliness of approvals

The device consulting company Emergo has produced a series of country specific summary sheets that seek to document the regulatory process for medical devices and associated timeframes, based on its experience with international regulators. Emergo notes that the timeframes provided are ‘typical’, but that submissions may take longer to process depending on the specific circumstances of the product.²² Because classification systems vary between jurisdictions, the data is not directly comparable, but it gives some sense of ‘typical’ timeframes to receive marketing approval for various classes of devices from international regulators.

According to the Emergo summary sheets:

·           In the US approval timeframes are typically: 1 month for US Class I devices; 3-6 months for US Class II devices and 18-30 months for US Class III devices.

·           In Europe the approval timeframes are typically: <1 month for Class I devices; 3-5 months for Class I Sterile or Measuring devices; 3-5 months for Class IIa devices; 3-6 months for Class IIb devices; and 6-9 months for Class III devices.

·           In Canada the approval timeframes are typically: 2-4 months for Canadian Class I devices; 1-2 months for Canadian Class II devices; 4-5 months for Canadian Class III devices; and 6-8 months for Canadian Class IV devices.

·           In Japan the approval timeframes are typically: ≤ 1 month for Japanese Class I devices; 3-5 months for Japanese Class II devices; 7-9 months for Japanese Class III devices; and 13-16 months for Japanese Class IV devices.

·           In Australia the approval timeframes are typically: <1 month for Class I devices; 2-3 months for Class I Sterile or Measuring devices; 2-3 months for Class IIa devices; 2-3 months for Class IIb devices; and 7-14 months for Class III devices. These timeframes are based on the assumption that the device has already been through a European conformity assessment and has a CE Marking. Emergo further notes that:

…the TGA reserves the right to perform an Application Audit on any submission, regardless of the classification or CE Marking status. A Level 2 Application Audit can lengthen review times by 9-10 months or more. Class III device applications are automatically audited by the TGA.²³

While this data provides a somewhat imperfect basis for comparison, it gives support to industry assertions that the Australian regulatory process for devices lacks timeliness when compared to some of its overseas counterparts, such as Canada and the EU.

3.3.1.1  Predictability

As noted previously in respect to medicines, while timeliness of approvals is important, another common efficiency measure is the predictability of the review process. In discussions with device manufacturers, a number emphasised that predictability was as important, if not more important, than was the actual time taken to approve the device. In the absence of this predictability, and faced with device approval timeframes that can vary from months to years, device manufacturers are unable to plan for the marketing of their device in Australia or in overseas markets that require Country of Origin approval.

The Panel was unable to access any independent benchmarking data in respect of predictability. However, anecdotal reports from industry to the Panel suggest that TGA timeframes are highly unpredictable and this would seem to be borne out by data from the most recent TGA key performance indicators report. The report indicates that 100 per cent of conformity assessments were completed within the statutory timeframe of 255 days, but performance in respect of compulsory  and  non-compulsory  audits  was  variable  (see Table 3).

Table 3: Medical Device Application Audits completed within target timeframes - 2014*

*Source: Therapeutic Goods Administration (2015, January) TGA Key Performance Indicators Version 1.0. p. 9.

Having reviewed the data available, the Panel concluded that the predictability of the TGA review process for medical devices is problematic.

3.3.2    Would use of overseas assessment reports improve timeliness and reduce duplication?

The regulation of medical devices in Australia differs from that of medicines in that it already makes considerable use of overseas conformity assessments in assessing devices for inclusion in the ARTG. Conformity assessment procedures are the processes undertaken by a manufacturer to ensure a medical device complies with the regulatory requirements for quality, safety and performance, as set out in the Essential Principles.ⁱⁱ A person seeking to include a medical device or IVD in the ARTG must be able to substantiate the application of those conformity assessment procedures to the device, usually relying on certification issued by a ‘conformity assessment body’ (CAB).

The TGA is the only body that can provide conformity assessment certification for the highest risk medical devices, i.e. those that contain medicines or tissues of animal, biological or microbiological origin, or Class 4 IVDs. For other medical devices and IVDs the TGA may accept certification from certain other CABs as evidence of an appropriate conformity assessment procedure. Given the close parallels between the European and Australian regulatory frameworks for devices, conformity assessment certification is generally accepted from European CABs, which are known as ‘notified bodies’.²⁴

Industry stakeholders are broadly supportive of the use of EU conformity assessments and many would like to see their use extended to higher risk medical devices. In addition, concerns were expressed about the additional assessment undertaken by the TGA as part of its ‘application audits’. The Act (s 41FH) provides that the TGA may select for an application audit any application for a kind of medical device to be included in the ARTG and must  select for audit specific kinds of applications as provided for in the Regulations. An application audit involves checking some or all aspects of the application and certification,

ii See Schedule 1 of the Therapeutic Goods (Medical Devices) Regulations 2002.

with the nature of the audit and the documentation required for assessment dependent on the level of risk associated with the medical device.²⁵ Where the audit is mandatory, audit fees apply. This additional layer of assessment is viewed as unnecessary duplication of processes that have already been carried out by an EU notified body, resulting in delayed access by Australian consumers to new technology.

Greater reliance on EU conformity assessments, or those from other comparable CABs, with minimal or no further assessment by the TGA, would undoubtedly result in more timely access to new medical devices by Australian consumers and reduce costs and regulatory burden on device manufacturers. For example, the Emergo data suggests that:

·           Reliance on EU certification for the highest risk devices could potentially reduce approval times for these medical devices by up to eight months.

·           Removal of the need for assessment audits could reduce approval timeframes by 9-10 months, and reduce industry costs in respect of audit fees and allocation of staff time to respond to questions and provide data.

However, the Panel questions whether such an approach would result in an appropriate balance between safety and timely access.

In recent years the European system has been shown to have systemic weaknesses, which has led to concerns about the quality of conformity assessment undertaken by some EU notified bodies. A series of articles published in the BMJ²⁶ raised a number of issues including:

·           The fact that European notified bodies are private commercial entities may create a conflict of interest and brings into question the extent to which the regulatory system prioritises patient health and safety over financial or trade facilitation considerations.

·           Lack of transparency about the basis of marketing approvals issued by European notified bodies.

·           Concerns that the level of evidence to support the marketing approval of many higher risk devices is insufficient to allow safe widespread use.²⁷

A report produced by the FDA in May 2012 also found concerns with the European conformity assessment system, asserting that it has resulted in harm to patients through the application of less stringent assessment standards than those that apply in the US.

Because of the EU’s lower approval standard and degree of oversight, high-risk devices are more often approved first in the EU than in the US. The lack of valid evidence of effectiveness has several negative effects on patients, however. As shown in this report, the EU’s reliance on limited testing, generally without significant testing in humans, can fail to predict dangerous risks and ineffective treatment in actual use. As a result, approval of devices without a valid

demonstration of effectiveness has permitted the marketing of products in the EU that turned out to cause severe harm to patients, either because the testing was inadequate to reveal the device’s risk or because use of an ineffective device denied patients access to effective treatments for serious diseases. In addition, the lack of valid data on effectiveness has caused some of the biggest EU countries to delay reimbursement for some approved high-risk devices until a second, sometimes lengthy, cost-effectiveness review is completed. In those cases, EU approval of a device does not necessarily mean that it is available to patients there.

The EU system for approving devices has now also come under criticism from the European medical community because of the number of devices that have turned out to be dangerous or ineffective. The medical community has also expressed dissatisfaction with the inconsistent review standards of the private bodies that approve devices in the EU and the secrecy of the approval process there.²⁸

Concerns have also been raised in respect to the regulation of devices by other countries, such as the US. A recent examination of the US regulatory system for devices found issues with the process to list medical devices based on an equivalent approved (predicate) device (i.e. the 510k process), including a lack of scientific data to support the claim of substantial equivalence, particularly clinical data.²⁹

These recent criticisms of EU and US device regulation highlight that, unlike the regulatory framework for medicines, which is relatively mature and stable, the regulation of medical devices is still evolving. The nature and extent of assessment undertaken can vary markedly between countries and this makes dependence on conformity assessments conducted by overseas CABs potentially fraught, particularly in respect of higher risk devices.

3.4     Use of overseas assessments

As outlined above, there is clearly potential for the Australian NRA to make greater use of overseas assessment reports in considering medicines and medical devices for inclusion in the ARTG. To do so will reduce regulatory burden and costs to industry and improve the timeliness of consumer access to innovative medical device technologies and possibly, in a more limited range of circumstances, to medicines. There are, however, risks associated with adopting such reports without any additional oversight or consideration.

In order to manage these risks it is essential that Australia maintain its capacity to undertake assessments of medicines and medical devices for safety quality and efficacy; and continue to make an independent decision about the inclusion of therapeutic goods in the ARTG which has regard to, but is not bound by, decisions of comparable overseas regulators. These issues are discussed below. In addition, appropriate management of risks will necessitate: clear and transparent criteria by which Australia identifies ‘trusted’ or comparable overseas NRAs; and the development and implementation of enhanced post-

market monitoring of medicines and devices to ensure that any emerging safety concerns are detected as soon as possible. These issues are explored in detail later in this report.

3.4.1  Independent capacity to undertake assessments and make decisions

3.4.1.1  Medicines

In the medicines space many stakeholders, while supportive of the Australian NRA making greater use of overseas assessment reports in certain circumstances, did not want to see any diminution of Australia’s capacity to undertake such assessments itself. Australia needs to retain capacity to undertake assessments of new medicines for a number of reasons.

Firstly, full assessment of applications for registration in the ARTG is likely to remain the only viable approach for the market authorisation of vaccines. The difficulty with mutual recognition of other jurisdictions’ reports and/or decisions in relation to vaccines includes:

·           Alignment with seasonal influenza in the different hemispheres, where Australia can have a different antigenic composition of the product from the Northern Hemisphere, which also varies annually.

·           The specific needs and population groups targeted in Australian immunisation programmes, for example, immunisation for Q fever.

·           A greater need to consider differences in disease prevalence between the different jurisdictions. Northern Hemisphere regulators encounter a different mix of tropical and subtropical diseases than Australia.

Secondly, given the apparently increasing trend by some major international pharmaceutical companies to make simultaneous applications to first and second-tier regulators, including the TGA, it is important for industry and Australian patients that this pathway remains available.

Finally, even where a medicine has already been approved by a comparable overseas regulator, and the sponsor is seeking to rely on that assessment report for registration of the product in Australia, some further assessment by the Australian NRA is likely to be required. This assessment requires access to the same set of skills and expertise as is required to undertake a de novo assessment of the data dossier. This further assessment may relate to: the need to ensure safety, quality and efficacy where there are differences between the product to be registered in Australia and that assessed overseas; and/or to ensure that Australian contextual issues are addressed.

That is, it is not uncommon for aspects of a new medicine, such as dosage or site of production, to differ in different markets. This may be to ensure the medicine is most appropriate to conditions, such as clinical practice standards or climate, applicable to that market, or to reflect the company’s production and distribution strategy. Thus, while it is unusual, but not unknown, for a new medicine to be approved by one major regulator and

be rejected by another, it is quite common for different regulators to approve different dosage regimes, different indications, or different conditions of use for the same medicine. For example: dosage levels for Febuxostat, a drug used to manage gout, are 80-120mg daily in Europe and New Zealand; 80mg daily in Canada; and 40-80mg daily in the US and Australia; while the recommended duration of treatment with Sofosbuvir, for the management of genotype 3 Hepatitis C, in Australia is 16 weeks while the FDA requires       24 weeks treatment. These differences reflect unique conditions within jurisdictions, such as clinical practice standards, which the regulators take into account in making a determination.

Examples of where Australia’s demographics, climatic conditions, disease epidemiology, and clinical practice have the potential to impact product safety or analyses of benefit and harm and which, therefore, may necessitate further examination of an application for inclusion of a medicine in the ARTG include:

·           Significant climatic variations which, while not unique to Australia, mean that stability, storage and transportation issues need to be closely assessed in the non-clinical evaluation, with cold chain challenges particularly important for vaccines.

·           Some quite unique patterns of medicine use when compared to other markets such as the US and Europe. This may impact the analysis of drug interactions and the nature of warnings required in Product Information (PI) and Consumer Medicines Information (CMI).

·           Consideration of whether genetic polymorphism or mutation frequency may impact the risk-benefit balance.

·           The Australian categorisation system for prescribing medicines in pregnancy differs from the categorisation systems utilised by other regulators, such as the FDA, and almost certainly reinforces a more conservative approach by Australian doctors compared with their colleagues in other jurisdictions.

·           Prescribing practices differ between jurisdictions. For example, the synthetic thyroid hormone levothyroxine is the most commonly prescribed medicine in the US and the third most prescribed in the UK, but is not in the top ten prescriptions in Australia. Yet there is no apparent concomitant difference in the prevalence of hypothyroidism between Australia and these other countries.

·           Medicines may be used at different stages of treatment of disease in different countries. For example, a medicine that is approved as a first line treatment in the US may be approved as a second or third line treatment in Australia.

These examples reinforce the importance of ensuring that the Australian NRA has both the capacity to undertake assessments of medicines and the capacity to make an independent decision about the inclusion of a medicine in the ARTG and the terms under which this

marketing approval is granted. To abrogate this sovereign right would undermine the Australian regulator’s capacity to undertake an independent risk-benefit assessment which takes into account the Australian context, including population parameters and clinical practice settings.

3.4.1.2  Devices

In respect of medical devices, some stakeholders indicated that the Australian regulator should not undertake conformity assessments of medical devices at all. They noted the diversity of devices on the market and the rapid evolution of device technology, and questioned the capacity of the Australian NRA to have ready access to the full range of technical expertise required to undertake device assessments. Difficulty in accessing such expertise was cited as a possible reason that the TGA’s approval timeframes lagged behind a number of its international counterparts. Furthermore, these stakeholders raised concerns about a potential conflict of interest in the Australian NRA operating as both a conformity assessment agency and a regulator ‘assessing’ (through for example, the application audit process) conformity assessments undertaken by other NRAs.

This view was by no means unanimous however. A number of stakeholders, including an industry peak and some local device manufacturers, indicated to the Panel they want to continue to have capacity to seek a conformity assessment domestically, although they wanted this to occur in a timely and predictable manner (with predictability highlighted as being particularly important). They also expressed the view that it was essential to the local industry that health practitioners and consumers had confidence in the quality and safety of medical devices and that, until issues with the EU regulatory system were corrected, there was potential for this to be undermined should Australia transition to total reliance on EU conformity assessments.

Consumers and health practitioners also had a strong interest in ensuring that devices available on the Australian market, particularly high-risk implantable devices, were of high quality, fit for purpose, and adequately assessed in terms of safety. They expressed concern about any diminution of the role of the Australian NRA in this space, in the absence of assurances about the quality of overseas device assessments. They also called for much stronger post-market monitoring of medical devices, noting that there is an element of risk associated with all medical devices and that many problems with medical devices cannot realistically be detected until there has been extensive market experience with the use of the device.

Regardless of whether the Australian NRA undertakes the conformity assessment of a device or devolves this to overseas assessment bodies, a number of stakeholders emphasised the importance of Australia remaining the final arbiter of whether a device is included in the ARTG. It was argued that broader health policy settings differ between countries and there are circumstances in which this policy context is important in assessing

the risk-benefit balance of a new medicine or medical device. For example, Australia’s stance on tobacco control is much stronger than that adopted by many countries, and prevalence rates of smoking are lower. These would be relevant consideration in assessing the likely harms and benefits in the Australian context of devices such as e-cigarettes.

Having considered the arguments, and in light of ongoing concerns that have been raised about the regulation of devices in other markets, such as the EU and US, the Panel formed the view that Australia needs ongoing capacity to assess and/or audit devices, particularly high-risk devices. Should confidence building activities currently underway in the EU, and between Australia and the EU, bear fruit, however, greater devolution of these activities might be considered in the future. Regardless of any future devolution of device conformity assessments, the Panel is of the view that Australia should always retain its capacity to make an independent decision about the inclusion of a medical device in the ARTG, rather than simply rely on an overseas assessment.

1 World Health Organization (2003, November), WHO Policy Perspectives on Medicines - Effective medicines regulation: ensuring safety, efficacy and quality, Geneva, pp. 1-2

2 Therapeutic Goods Administration (2014), Half-yearly performance reports: January to June 2014, version 1.0, October 2014, p. 6.

3 Department of Health (2014), Annual Report 2013–2014 Volume 2, Commonwealth of Australia, Canberra, p. 359.

4 Australian Government Department of Prime Minister and Cabinet (2014), Industry Innovation and Competitiveness Agenda, p. IX. Available at:

https://www.dpmc.gov.au/sites/default/files/publications/industry_innovation_competitiveness_agenda.pdf         5 Centre for Innovation in Regulatory Science (2014a), The impact of the changing regulatory environment on the approval of new medicines across six major authorities 2004-2013, R&D Briefing 55, Centre for Innovation in Regulatory Science Ltd, London, 16 December 2014.

6  Ibid., p. 2.

7  Ibid., p. 1.

8 Ibid., pp. 9-14.

9 Ibid.

10 Centre for Innovation in Regulatory Science (2014b), Availability of New Medicines. Characterising the factors influencing drug roll out to six mature markets. R & D Briefing 53, Centre for Innovation in Regulatory Science Ltd, London.

11 Ibid., pp. 5-8.

12 Centre for Innovation in Regulatory Science (2014a), op.cit., p.2.

13 Ibid.

14 Centre for Innovation in Regulatory Science (2014b), op. cit.

15 Ibid. (2014b).

16Centre for Innovation in Regulatory Science (2014a), op. cit.

17Medew, J., (2014, December 4), ‘Cost of life under microscope as new cancer drug on wait list,’ Sydney Morning Herald. Accessed online on 25 February 2015 at: http://www.smh.com.au/national/health/cost-of- life-under-microscope-as-new-cancer-drug-on-wait-list-20141204-120g70.html

18 Australian Government Department of Finance (2014, July), Australian Government Cost Recovery Guidelines. Resource Management Guide No. 304, 3^rd Edition, Commonwealth of Australia, Canberra, p. 3. 19 CIRS (2014b), op. cit., p. 17.

20 Pan American Health Organization, (2001), A Model Regulatory Program For Medical Devices: An International Guide, PAHO, Washington D.C, p. 11.

21 World Health Organization, Medical devices regulations webpage. Accessed online on 25 February 2015 at: http://www.who.int/medical_devices/safety/en/

22 Emergo (2014) Download regulatory Process Charts and Regulatory Timelines. Available at: http://www.emergogroup.com/resources/download-regulatory-process-charts

23 Ibid.

24 Therapeutic Goods Administration (2014, October 15) RIS: Premarket assessment requirements for Australian manufactured medical devices, p. 29.

25 Therapeutic Goods Administration (2013, June), Regulation Impact Statement: Changes to premarket assessment requirements for medical devices V2.0. p. 69.

26 See for example: Cohen, D. (2011, May 21), ‘Out of Joint’, BMJ 2011;342:d2905; Cohen, D (2012, October

24), ‘EU approval system leaves door open for dangerous Devices’, BMJ 2012;345:e7173; Storz-Pfennig P., et. al., (2013, May 11) ‘Trials are needed before new devices are used in routine practice in Europe’, BMJ 2013;346:f1646; Cohen, .D (2012, October 23), ‘Faulty hip implant shows up failings of EU regulation’, BMJ 2012;345:e7163. Accessed online on 28 October 2014 at: http://www.bmj.com/content/345/bmj.e7163.

27 Therapeutic Goods Administration (2013, June), op. cit., pp. 9-10.

28 Food and Drug Administration (2012, May), Unsafe and Ineffective Devices Approved in the EU that were Not Approved in the US. Accessed online on 25 February 2015 at: http://www.elsevierbi.com/~/media/Supporting%20Documents/The%20Gray%20Sheet/38/20/FDA_EU_Devic es_Report.pdf

29 Zuckerman D., Brown P., and Das A., (2014, November 1) ‘Lack of publicly available scientific evidence on the safety and effectiveness of implanted medical devices’ in JAMA Internal Medicine, 174(11):1781-7. Published online September 29, 2014.

38

CHAPTER FOUR: REGULATORY FRAMEWORK FOR MEDICINES

The Therapeutic Goods Act 1989 divides therapeutic goods into three broad categories: biologicals, medicines and medical devices. Unless exempt, biologicals and medical devices must be 'included' in the Australian Register of Therapeutic Goods (ARTG) and medicines must be 'registered' or 'listed' in the ARTG before they may be supplied in, or exported from, Australia. The Act defines a medicine as:

(a)                          therapeutic goods (other than biologicals) that are represented to achieve, or are likely to achieve, their principal intended action by pharmacological, chemical, immunological or metabolic means in or on the body of a human; and

(b)                          any other therapeutic goods declared by the Secretary, for the purpose of the definition of therapeutic device, not to be therapeutic devices.

In general terms, medicines include: drugs that must be prescribed by a doctor, dentist or other approved prescribers (prescription medicines); drugs available without a prescription, which may be purchased from pharmacies or in some cases from other outlets such as supermarkets (over-the-counter (OTC) medicines); and complementary medicines, including vitamins, herbal and traditional medicines. This chapter addresses the regulatory framework for prescription and OTC medicines. The regulatory framework for complementary medicines will be addressed in the Panel’s second report.

4.1     Current regulation of medicines

The Australian NRA regulates medicines through three basic procedures:

•          Pre-market assessment (before entry of the medicines onto the ARTG).

•          Post-market monitoring and enforcement of standards (once the medicine is in the ARTG).

•          Licensing of Australian manufacturers and verification of overseas manufacturers’ compliance with the same standards as their Australian counterparts.

The balance between the required pre-market assessment and subsequent post-market monitoring depends on what is already known about the particular medicine (or about similar medicines) at the time that the product is assessed by the NRA. Once a medicine is approved and entered in the ARTG, the NRA:

•          continues to monitor the product in the market through pharmacovigilance activities, which includes information collection, monitoring, evaluation, and risk management; and

•          works with overseas NRAs and conducts regular inspections of manufacturers, both in Australia and overseas, to ensure they continue to meet manufacturing standards.

4.1.1  Risk-based framework

Australia’s regulatory framework for medicines is risk-based. That is, differing regulatory standards are adopted in the assessment and management of medicines according to the perceived risk to the public of their use. Products carrying a higher risk, including all prescription medicines, receive a significantly higher degree of pre-market assessment compared to lower risk medicines with well known, and/or tried and tested, ingredients. Higher risk medicines must be registered in the ARTG and this is indicated by the inclusion of an AUST R number on the product label. Lower risk medicines must be listed in the ARTG and are required to display an AUST L number on the product label.

Risk assessment of products is also utilised to determine how consumers can gain access to a medicine. For example, a low-risk medicine may be safely sold in a supermarket, whereas a higher risk medicine may only be supplied after consultation with a health professional. Whether a medicine is classified as prescription, OTC, or is available more generally through, for example, supermarkets, is determined by the scheduling of substances on the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP), known as the Poisons Standard.

4.1.1.1  Registered medicines

Australia’s regulatory framework for medicines is risk- based. That is, differing regulatory standards are adopted in the assessment and management of medicines according to the perceived risk to the public of their use.

Higher risk medicines, including all prescription medicines and the vast majority of OTC medicines, including commonly used drugs such as aspirin and paracetamol, must be registered in the ARTG following an evaluation by the NRA. A sponsor may apply for registration of a medicine containing a new chemical entity via two pathways, known as ‘Category 1’ and ‘Category 2’, respectively. Category 1 is the pathway used in the vast majority of cases and involves the submission of a complete data dossier to the NRA for     de novo evaluation. Applications made via the Category 1 route need to be determined within a maximum of 255 working days of receipt of the application. The Category 2 pathway is restricted to medicines that have been approved for general marketing in two other acceptable countries; which have the same formulation, directions for use, and indications as approved in those two countries; and for which two independent evaluation reports are available. The sponsor is required to submit a completed data dossier along with the two un-redacted evaluation reports for evaluation by the NRA. Applications made via the Category 2 route need to be determined within a maximum of 175 working days of receipt of the application.ⁱ

i Part 3A, s 16C, Therapeutic Goods Regulations 1990.

On receipt of an application to register a new chemical entity (NCE), the Australian NRA conducts a detailed evaluation of the data provided in order to establish the quality, safety and efficacy of the proposed product for the proposed usage (indication). This evaluation may include seeking further information or clarification of the data from the sponsor, and/or seeking independent advice from clinical and scientific experts via a number of advisory committees. The purpose of this evaluation is to assist the NRA’s delegated decision maker, usually a senior medical officer, to assess the balance between the benefits and the risks of using the medicine, so that (s)he can decide whether or not to grant approval for the product to be registered in the ARTG for its specified use. If the product is accepted for registration in the ARTG it can then be marketed in Australia for the indications included in the ARTG, subject to any conditions specified by the NRA.

Similarly, application must be made to the NRA to register a new indication for a medicine already listed in the ARTG or to register a generic medicine or a biosimilar in the ARTG. In respect to generic medicines, the NRA conducts an evaluation of the bioequivalence of the generic to the originator product, as well as reviewing information concerning the quality of the medicine. In relation to biosimilars, the NRA conducts an evaluation of comparability studies substantiating the similar nature in terms of quality, safety and efficacy of the biosimilar to the reference product. Australia has adopted a number of the EMA’s guidelines for assessment of biosimilars, as well as an International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guideline on the assessment of comparability.¹

4.1.1.2  Listed medicines

Lower risk medicines are listed, rather than registered, in the ARTG before being supplied in Australia. Most listed medicines are complementary medicines, but there are a small number of OTC products, for example menthol throat lozenges and some cough and cold preparations, that are listed in the ARTG. Most sunscreens are also included in the ARTG as listed medicines.

A listed medicine can only be marketed in Australia if:

1.        It contains nothing but pre-approved low-risk ingredients. These pre-approved ingredients have been evaluated by the NRA for quality and safety but not for efficacy.

2.        The manufacturing site (if in Australia) is inspected and licensed by the NRA or, if manufactured in a facility overseas, the site has been assessed by the NRA and determined as meeting appropriate standards.

3.        It does not make claims or imply that it will be useful in the treatment or prevention of serious illnesses that would require the involvement of a health professional.²

Unlike registered medicines, the TGA does not individually evaluate listed medicines before they are entered in the ARTG. Rather, when listing a medicine in the ARTG, the sponsor

must make certifications about quality; compliance with labelling, packaging and Good Manufacturing Practice (GMP) standards; and use of approved ingredients. The sponsor must also certify that they hold evidence to support any therapeutic claims. This allows for early market access, with sponsors of listed medicines generally able to supply their product in Australia within 48 hours of submitting an electronic application.

4.1.1.3  Scheduling

The Scheduling Policy Framework is a ‘national system for applying access restrictions on all poisons’³, including medicines for human use, veterinary, agricultural, domestic and industrial chemicals where there may be risk to human health and public safety.⁴ Under the Scheduling Policy Framework, substances are classified according to the level of regulatory control required to protect public health and safety. As such, scheduling controls how medicines and poisons are made available to the public by considering the active ingredient (substance) contained within the medicine or poisonⁱⁱ and the way in which the medicine is used and packaged. Under the Act, a person may apply to amend the Poisons Standard through addition of a new substance or rescheduling of an existing substance.⁵

Medical substances intended for human therapeutic use may be classified as Schedule 8 (controlled drugs), Schedule 4 (prescription medicines), Schedule 3 (pharmacist only) and Schedule 2 (pharmacy only) or may be unscheduled. Medicines containing substances on Schedules 4 and 8 may only be sold with a prescription, whereas medicines on Schedules 3 and 2 may be sold in pharmacies. In some states, Schedule 2 medicines may also be sold by licensed medicine sellers. Unscheduled medicines may be sold generally, for example, through supermarkets. Because the scheduling process considers the way in which the substance is to be sold, as well as the substance itself, a medicine containing the same active substance may appear on several Schedules. For example, ibuprofen solid dosage forms sold in pack sizes of no more than 25, and with a maximum 200mg per dose, are unscheduled and may be sold generally, for example in a supermarket. However, ibuprofen solid dose units at higher dosages (up to 400mg) in pack sizes of up to 50, are included on Schedule 3 and can only be sold with the advice of a pharmacist.

4.1.1.4  Post-Market Monitoring

Once a medicine has been registered or listed in the ARTG, it is subject to monitoring by the NRA. The extent of this monitoring depends on the risk classification of the medicine. Post- market monitoring by the NRA is focused on the safety of the medicine rather than on its efficacy and, as such, generally includes the collection and analysis of adverse event reports from consumers, health professionals and industry. Reports from overseas NRAs or from the medical and scientific literature are also assessed. In addition, sponsors of higher risk

ii Generally combination products are scheduled in line with the substance that is scheduled more restrictively. There are instances, however, where a combination product has been scheduled more restrictively than either of its components (e.g. the combination of ibuprofen and paracetamol).

prescription medicines may be required to comply with a Risk Management Plan (RMP) which incorporates activities to identify and manage risks relating to the particular medicine. For these medicines, compliance with the RMP will be a condition of ongoing registration in the ARTG.

The aim of these pharmacovigilance activities is to identify any emerging safety problems as

quickly as possible so that remedial actions can

Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.

WHO (2002)

be taken if necessary. Active pharmacovigilance  is particularly important for new medicines, as these have generally only been assessed in clinical trial conditions where the attributes of patients using the product are tightly controlled. When the product is used in the real world, by patients with a range of demographic profiles and with comorbidities, unforeseen adverse events and contraindications for the use of the

medicine can emerge. Where problems are detected the NRA is able to take a range of regulatory actions, from continued monitoring through to product withdrawal.

Post-market monitoring also occurs in respect of compliance with regulatory requirements related to, for example, the manufacture and promotion of the medicine.

4.1.1.5  Manufacture of Medicines

Medicines registered or listed in the ARTG in Australia are required to comply with internationally accepted manufacturing principles developed by the Pharmaceutical Inspection Cooperation Scheme (PIC/S). Unless subject to specified exemptions, medicines manufactured in Australia cannot be registered or listed in the ARTG unless each step in their manufacture has been carried out by a licensed manufacturer. If any (or all) of the steps in the manufacture of a medicine have been carried out overseas, listing or registering in the ARTG is subject to those steps being performed to the same standard expected of Australian licensed manufacturers.

In order to satisfy itself, the NRA may inspect the overseas premises or, if the premises have been inspected and authorised by a trusted overseas counterpart, the NRA may accept this authorisation. The TGA has entered into several international agreements with overseas regulators for this purpose, and the vast majority (over 90 per cent) of overseas medicine GMP applications are ‘cleared’ based on these inspections, rather than requiring the TGA to conduct an on-site inspection.

4.1.1.6  Advertising of Medicines

The regulatory framework for medicines places conditions and limitations on the advertisement of medicines to health professionals and direct-to-consumers. Both

prescription and OTC medicines may be promoted to health professionals. Such promotion must comply with requirements of:

·           the Competition and Consumer Act 2010;

·           section 22(5) of the Therapeutic Goods Act 1989 (the Act), which establishes an offence where therapeutic goods are advertised with indications other than for which they have been accepted in the Register; and

·           any other conditions which may be assigned to the marketing approval of the product.

It is also a condition of registration of medicines in the ARTG that the promotion of all prescription products, whether by a member or non-member of Medicines Australia, complies with the requirements of the Medicines Australia Code of Conduct.⁶

In terms of direct-to-consumer advertising, this is not allowed for prescription medicines and most Schedule 3 (pharmacist only) medicines. Other OTC medicines may be advertised direct-to-consumers but are subject to pre-approval in most circumstances.

4.2     Assessment of current regulatory framework

Submissions to the Review were generally highly supportive of the current risk-based regulatory framework for medicines. The current framework has been in place since 1989, although it has undergone modification from time to time, including to increase harmonisation of Australian requirements with those of overseas NRAs. For example, in 2004 the TGA adopted the Common Technical Document – a set of specifications for a dossier for the registration of medicines developed by the ICH. The regulatory framework is, therefore, well established and appeared to be reasonably well understood by stakeholders.

In terms of implementation of the framework, the consistent view expressed to the Panel by industry, professional and consumer groups was that the TGA was a highly skilled organisation which undertook thorough and sophisticated evaluations of applications for registration of new medicines and which was regarded as a benchmark agency and role model in the Asia-Pacific region. As documented in Chapter Three, the TGA currently performs reasonably well when benchmarked against comparable overseas NRAs on approval timeframes for new medicines and very well when benchmarked against these NRAs on predictability of approval timeframes.

While there was a level of satisfaction with the regulatory framework for medicines, and a sense that the framework had generally served Australia well, there was also recognition that there were opportunities to improve the efficiency and effectiveness of the system in relation to, for example:

·           Pre-market assessment of medicines, including opportunities for expedited assessments and greater engagement with the work of overseas NRAs.

·           Post-market regulation, including simplified processes for managing variations to ARTG entries and improved post-market monitoring.

·           The consistency and transparency of regulatory processes, such as the scheduling of medicines.

In addition, a number of stakeholders commented that a review of the framework was timely, as rapid advancements in the development of medicines and medical technologies necessitate a regulatory system that is flexible and responsive enough to adapt to future trends. Such trends are expected to include: increased ‘personalisation’ of medicine as a result of the identification of biomarkers and other emerging development technologies such as 3D printing; and an increasing development of drug-diagnostic and drug-devices combinations.⁷ These trends pose challenges to the Australian regulatory system, including in terms of the timeliness of assessments where products are subjected to regulation under multiple frameworks (for example, as both a medicine and a device).

Having considered the issues raised, the Panel concluded that, while the regulatory framework for medicines is largely sound, there are a number of areas in which the framework could be improved. These issues are discussed below and can be broadly categorised as:

1.        The provision of multiple pathways for pre-market assessment of new chemical entities, and twin pathways for pre-market assessment of generic medicines and biosimilars.

2.        Enhanced transparency of scheduling decisions and decisions about advertising Schedule 3 medicines.

3.        Changes to post-market regulation with a view to simplifying and streamlining processes, and enhancing post-market monitoring.

4.        Threshold issues for ‘therapeutic goods’.

4.3     Proposed reforms to the regulatory framework for medicines

4.3.1  Pre-market assessment of new chemical entities

While stakeholders were generally supportive of the pre-market assessment of medicines in Australia, a number expressed concern about the capacity of the system to provide timely access to novel therapies in all circumstances. In particular it was noted that a number of medicines, including oncology drugs, were available in overseas markets several years before becoming available in Australia. As noted in Chapter Three, a delay in the availability of novel medicines on the Australian market is most likely the result of medicine manufacturers lodging their application for registration later in Australia than in larger markets, such as the US or Europe. The lack of an expedited approval process in Australia may also be a contributing factor. In circumstances where novel medicines were viewed as potentially life-saving or life-changing, further assessment by the NRA of the medicine,

which had received registration status from a comparable overseas NRA, was seen by some consumer and public health groups as unnecessary and a barrier to patients accessing these medicines.

The Panel identified three options to speed market access to novel medicines in Australia. Firstly, pursue work-sharing arrangements with comparable overseas regulators for the assessment of medicines that have been submitted simultaneously to multiple NRAs. Secondly, revisit the Category 2 registration pathway to make it easier for sponsors to utilise an assessment from a comparable overseas regulator. Thirdly, restore capacity for the Australian NRA to undertake an expedited assessment of a new medicine in defined circumstances. Each of these options is discussed below.

4.3.1.1  Work-sharing arrangements

According to the TGA, there has been a trend in recent years for some major international pharmaceutical companies to make simultaneous applications to first and second-tier regulators, including the Australian NRA. Where this occurs, work-sharing between the Australian NRA and a comparable overseas NRA has the potential to reduce approval times in both markets. This approach would allow the two NRAs to work simultaneously on different parts of an evaluation report for a new medicine. For example, one regulator could look at the non-clinical modules of the application (e.g. pharmaceutical chemistry and toxicology) while the other regulator could simultaneously examine the clinical module of the application, which contains the clinical trials data. These would then be combined into a joint evaluation report which would be provided to decision makers in both countries.

A form of work-sharing has been occurring in the EU since 1995, when the EMA was established. Under the European model, while the EMA is a centralised licensing authority for most new active substances for all EU and European Economic Area - European Free Trade Association states, the evaluation work is typically shared between two member regulator countries, such as the UK and Germany.

The broader application of work-sharing is being explored internationally, with interest primarily from medium-sized regulators such as Australia, Canada, Brazil, Singapore and Switzerland. Implementation of work-sharing arrangements is complex, requiring a considerable commitment by each party to: gain an appreciation of each other’s legislation, regulatory policy platforms and evaluation processes; and build confidence in each other’s capabilities, including the ability to deliver reports in a timely fashion. Generic medicines have been the initial focus of work-sharing arrangements internationally. This is largely because of the high volume of new generic products globally, which has created an urgent need for more efficient evaluation processes. Work-sharing the assessment of generic medicines also provides an opportunity to establish protocols that provide a  ‘stepping stone’ for evaluation of the more complex and lengthy NCE applications.

The Panel is aware that the TGA has been actively engaged in promoting and participating in work-sharing arrangements internationally. In particular the TGA:

·           Commenced a joint work-sharing initiative with the Canadian NRA - Health Canada’s Health Products and Food Branch (HPFB) - in November 2011. The initiative aims to: enhance regulatory cooperation; reduce duplication of work common to both agencies; increase reliance on work undertaken by each other; and maintain sovereign decision making powers. The first phase of the initiative focused on work-sharing the assessment of generic medicines and demonstrated that cooperation between the TGA and HPFB is possible, realistic and achievable. It also provides a model to expand into other areas of cooperation such as NCEs, and with other comparable overseas NRAs.

·           Is an evaluator under an international pilot project that extends the European decentralised process to four regulators outside the EU: Australia, Canada, Chinese Taipei and Switzerland. Under the pilot, on the request of a generic pharmaceutical company, the EMA will share the assessment reports generated, in real time, with all four non-EU countries.

·           Is represented on the interim Management Committee for the International Coalition of Medicines Regulatory Authorities (ICMRA), and leads the generic medicines programme. The ICMRA, which was established in December 2013, involves 23 of the main global regulatory agencies and, among other things, is developing processes to support work-sharing more globally.

The Panel supports the continuation of efforts to put in place work-sharing arrangements with comparable overseas NRAs and extending such arrangements as soon as possible to the evaluation of new chemical entities.

4.3.1.2  Category 2 application pathway

There are currently two pathways to registration of a product in the ARTG – Category 1 and Category 2. The Category 2 pathway was introduced in 1992 following the Baume Report on the Future of Drug Evaluation in Australia.⁸ In preparing that report, Professor Baume asked much the same question as the Australian Government is asking today by adopting the principle that:

…if a system, service or product has been approved under a trusted international standard or risk assessment, Australian regulators should not impose any additional requirements unless it can be demonstrated that there is good reason to do so.⁹

Namely, ‘why do we need to re-evaluate drug products which have been approved for marketing in overseas countries which have comparable standards of regulation?’¹⁰

For reasons not dissimilar to those that we have outlined in Chapter Three, Professor Baume concluded that Australia needed to maintain its sovereign decision making capacity. However he went on to argue that this did not mean that ‘Australia needed to conduct a

completely new and independent evaluation based on unique data requirements’ and he recommended that there be a ‘simpler and quicker process where drugs have been approved elsewhere.’¹¹ As a result the Category 2 pathway was developed. But since its inception it has been rarely used and, as such, has failed to facilitate more rapid access by Australians to new medicines as envisioned by Professor Baume.

The current Category 2 pathway presents a number of barriers to its use. Firstly, it requires the provision of two un-redacted overseas assessment reports, which can be difficult for sponsors to obtain, especially from the FDA.

Secondly, the assessment reports must be from NRAs of countries specified in the Regulations, namely the US FDA, Health Canada, UK’s Medicines and Healthcare Products Regulatory Agency (MHRA), Sweden’s Medical Products Agency and the Dutch Medicines Evaluation Board. With the establishment of the EMA in 1995, the number of evaluations by the three European regulators has declined significantly. This effectively leaves, in most instances, only two agencies from which the two assessment reports can be obtained, one of whom (the FDA) does not generally release un-redacted reports. Thirdly,

One common question asked in Australia about drug evaluation is ‘Why do we need to re-invent the wheel?’ That is to say, why do we need to re-evaluate drug products which have been approved for marketing in overseas countries which have comparable standards of regulation?

Professor Peter Baume (1991)

application under the Category 2 pathway is restricted to medicines which have the same formulation, directions for use and indications as approved in those two countries.

Given the above, the Panel considers it would be appropriate to replace the existing Category 2 application pathway with a new Pathway Two that provides for:

·           a sponsor to request registration utilising one un-redacted de novo evaluation report from a comparable overseas NRA;

·           the establishment of a more practicable list of comparable overseas NRAs whose assessment reports may be relied upon; and

·           use of an overseas assessment report in circumstances where the medicine the sponsor is seeking to register in the ARTG is highly similar, but not identical, to the product approved by the overseas regulator.

The Panel’s proposed approach to implementation of Pathway Two is discussed in section

4.3.3 below.

4.3.1.3 Expedited approval

Across the globe, regulators of therapeutic products are facing increasing consumer demand for early access to novel therapies. In Australia, such advocacy often focuses on subsidised

access through the Pharmaceutical Benefits Scheme. However, the timeframes for TGA approval of such therapies and the lack of an expedited route of approval for medicines that are used to treat serious or life-threatening conditions which represent a major advancement in treatment or are used to treat conditions where there is significant unmet clinical need, have also been a subject of concern. Within this context, the capacity of the regulatory system to appropriately balance the benefits to consumers of having early access to promising new treatments with the risks of accessing therapies, the safety and efficacy of which are still being established, is becoming increasingly important.

As a result of Business Process Reforms implemented by the TGA in 2010, Australia no longer has the capacity to undertake expedited approvals of promising new medicines. In this regard Australia is out of step with comparable overseas NRAs, such as the FDA, EMA or Health Canada, all of whom have capacity to undertake expedited approval in some circumstances. Benchmarking data from the Centre for Innovation in Regulatory Science (CIRS)¹² indicates that expedited approvals represented between 10 and 39 per cent of all approvals of NCEs by overseas NRAsⁱⁱⁱ in 2013 and reduced median approval timeframes by between 123 and 318 days.

The two major regulators, the FDA and the EMA, have taken different approaches to expedited approval. The FDA has implemented four accelerated approval schemes, each of which has its own eligibility criteria and provides for varying intensities of FDA engagement and guidance. Capacity to undertake rolling reviews of data dossiers, which allows the sponsor to submit portions of a marketing application before submitting the complete application, and earlier approval of medicines based on a surrogate endpoint, are features of some of the schemes. As illustrated in Figure 7, two of these schemes – Fast Track and Breakthrough Therapy – seek to both facilitate product development as well as expedite product registration.

The FDA makes the decision whether to accept applications for these four schemes or alternatively to refer the sponsor back to the standard approval process. The fees payable by the sponsor for fast track approvals reflect the additional FDA effort involved in the schemes. The approval rate is about 50 per cent. While the regulatory consideration phase is accelerated under the four schemes, the main reported advantage to industry is assistance with design and facilitation of clinical trials.

In contrast, the EMA is conducting a pilot project on adaptive licensing, which it defines as:

…a prospectively planned, adaptive approach to bringing drugs to market. Starting from an authorised indication (most likely a ‘niche’ indication) for a given drug, through iterative phases of evidence gathering and progressive licensing adaptions concerning both the authorised indication and the potential further therapeutic uses of the drug concerned [adaptive licensing] seeks to maximize the positive impact of

iii Based on 2013 approval data from the FDA, EMA, Health Canada, Swissmedic and Japan’s PDMA.

new drugs on public health by balancing timely access for patients with the need to provide adequate evolving information on benefits and harms.¹³

Figure 7: FDA expedited development and approval schemes

Adaptive licensing utilises different evidentiary requirements, for example, Conditional Marketing Authorisation, based on the results of Phase 2 rather than full Phase 3 trials. This approach recognises the need for ongoing reassessment of the risk-benefit balance throughout the lifecycle of the medicine as experience is obtained with a patient  population. It is anticipated that commercial use of the medicine after conditional approval would commence in a small group of patients with a narrowly-defined indication and potentially be expanded as clinical experience with the medicine grows.

The EMA can also undertake an ‘accelerated assessment’ of a new medicine in certain circumstances, which reduces the assessment timeframe from 210 to 150 days.¹⁴

In its Review of Medicines and Medical Devices Regulation Discussion Paper, the Panel sought input from stakeholders on whether there was a need in Australia for expedited approval and, if so, what such a programme should look like. There was a high level of support for the development of an expedited approval pathway(s) from both industry and consumers, with submissions noting that earlier access to new medicines can have a  positive impact on patient care and patient outcomes.

Expedited approval programmes are offered by all of the major overseas NRAs and there is strong support from industry, professional and consumer stakeholders for the Australian NRA to have capacity to offer such programmes. As such, the Panel recommends that the registration pathways for new medicines include capacity to offer expedited approval. The features of such a pathway are discussed in section 4.3.4 below.

4.3.2  Pre-market assessment of generic medicines and biosimilars

Generic medicines

A generic product is a medicine that, in comparison to the originator (sometimes referred to as innovator) product:

•          has the same quantitative composition of therapeutically active substances, being substances of similar quality to those in the originator product; and

•          has the same pharmaceutical form as the originator product; and

•          is bioequivalent to an originator product, or considered to be therapeutically equivalent in the case of topical products; and

•          has the same safety and efficacy properties.¹⁵

The NRA will accept applications to register generic products in the ARTG without further safety and efficacy data where the proposed indications and dosage regimen are the same as those of the originator product and where the safety and efficacy data provided with the originator product are not ‘protected’ (section 25A of the Therapeutic Goods Act 1989 refers).¹⁶ As such, new generic medicines are generally only required to be assessed for quality and for bioequivalence to the original reference product. In respect to bioequivalence, the generic medicine must generally be shown to be bioequivalent to the corresponding strength of a leading brand (normally the originator product) as marketed in

Australia. However, in some circumstances, the NRA may accept bioequivalence studies carried out using samples of the originator product obtained from outside Australia, provided the sponsor can support this with evidence that the formulation of this product is the same as the formulation marketed in Australia.

The volume of applications to register new generic medicines in the ARTG far outweighs those for NCEs. That is, in the 12 months from 1 April 2013 to 31 March 2014, the TGA received 1,257 applications for new generic products, compared to 123 applications for NCEs.¹⁷ Given these volumes, any efficiencies that can be identified in the pre-market assessment process for generic medicines have the potential to be of substantial benefit to industry consumers.

The Panel notes that countries often do not have the same patent expiry and/or data exclusivity provisions for originator medicines and, as such, a generic medicine manufacturer may be able to apply for marketing approval of a generic product at different times in different markets. Australia may, therefore, be the first market for a generic medicine or it may be a subsequent market. Given this, the Panel is of the view that there should be two pathways to registration of a new generic medicine in the ARTG:

1.                  Pathway One, which would provide for de novo assessment of the data dossier for the generic medicine by the Australian NRA with or without work-sharing with a comparable overseas regulator. As noted in section 4.3.1.1, work-sharing arrangements between regulators, particularly for the assessment of new generic medicines, are being pursued internationally and this option may be worthwhile pursuing where submissions for marketing approval are lodged simultaneously with the Australian NRA and a comparable overseas NRA.

2.                  Pathway Two, which would provide for the sponsor of a new generic medicine to apply for registration of the medicine in the ARTG utilising one un-redacted de novo evaluation report from a comparable overseas regulator. The Australian sponsor would, however, also need to establish that the reference product used by the comparable overseas regulator when assessing bioequivalence was identical to, or interchangeable with, the Australian reference product.

The Panel’s proposed approach to the implementation of Pathway Two is discussed in section 4.3.3 below.

In respect of Pathway One, the Panel notes that the statutory timeframe for assessment of a data dossier for registration of a generic medicine in the ARTG is the same as that for an NCE, namely 255 working days. This is despite the fact that the assessment of a new generic medicine is generally less complex than that required for an NCE, as the safety and efficacy of the active ingredient has already been assessed and its use has been established in clinical practice. The Panel was advised that the TGA has been working with the Generic Medicines Industry Association to examine options to reduce the target timeframe for

assessment of new generic medicines to 180 days. The Panel supports this reduced assessment timeframe and would encourage its implementation as soon as possible.

Biosimilars

A biosimilar, or similar biological medicinal product, is a version of an already registered biological medicine that has a demonstrable similarity in physicochemical, biological and immunological characteristics, efficacy and safety, based on comprehensive comparability studies.¹⁸ Unlike generic medicines which have the same active ingredient as the reference product, biosimilars are complex heterogeneous mixtures of isoforms of the desired substance, meaning that evaluation of biosimilars cannot occur in the same way as evaluation of generic medicines. Instead, comprehensive comparability studies are required to generate evidence substantiating the similar nature in terms of quality, safety and efficacy of the biosimilar to the reference product.

Biosimilars are relatively new products and the approach to assessing them for market is  still evolving. For example, the FDA only approved the first biosimilar product for the US market on 6 March 2015.¹⁹ The EMA has had a longer history with biosimilars, having approved 19 products, with the earliest approvals occurring in 2007.²⁰ Australia has adopted a number of the EMA’s guidelines for assessment of biosimilars, as well as an ICH guideline on the assessment of comparability. The Panel is of the view that the Australian NRA should continue to pursue harmonisation of its regulatory requirements for biosimilars with those applying internationally.

While the volume of applications for biosimilars will be smaller than that for generic medicines, applications for marketing would be expected to occur at different times in different markets to coincide with the expiry of patents and/or data exclusivity periods for the originator products. As such, dual pathways for the registration of biosimilars in the ARTG would appear to be appropriate. These should reflect those described above for generic medicines, except in the case of Pathway Two, the sponsor would need to establish that the reference product used by the comparable overseas regulator when assessing the biosimilar and the Australian reference product were the same.

4.3.3  Implementation of Pathway Two

The successful implementation of Pathway Two for the registration of new chemical  entities, generic medicines, and biosimilars in the ARTG is dependent on a number of factors:

1.                  The identification of overseas NRAs that the Australian government and Australian consumers feel confident will conduct evaluations of medicines in a manner that is comparable to those conducted by the Australian NRA. This is essential to ensure that there is no diminution of safety standards for the Australian public;

2.                  The availability of un-redacted evaluation reports written in English from these overseas NRAs;

3.                  The implementation of enhanced post-market monitoring of medicines; and

4.                  Implementation of the pathway in a way that minimises regulatory costs and regulatory effort by product sponsors, without undermining public health protections.

4.3.3.1  Recognition of comparable overseas NRAs

If Australia is to base decisions about market access for medicines on an assessment made by an overseas NRA, then it is essential that Australia has confidence in the quality of such assessments. In short, the assessment must be conducted with a level of skill, expertise and rigour that is equal, or superior, to those undertaken by the Australian NRA.

Submissions to the Review provided a number of options for identifying comparable overseas NRAs. Some proposed the establishment of a list (as occurs under section 19A of the Act, which provides for the Secretary to specify ‘trusted’ countries for the purpose of

accessing medicines that are in short supply). Most commonly cited for inclusion on such a list were the two major regulators, the FDA and the EMA.

Other stakeholders considered that the selection of comparable overseas NRAs should be based on an assessment against a transparent set of criteria. This would provide for consistent assessment of overseas NRAs over time and provide a rationale for adding or removing countries from the list should their circumstances change. Within this context stakeholders considered that a range of factors should be taken into consideration including: the regulatory history of the NRA; the demographics and health system performance of the country; the volume of assessments of new chemical entities undertaken by the NRA; the process for review, including engagement of consumers during the assessment process; and adoption of international standards.

The Panel was attracted to a criteria-based approach to the selection of comparable overseas NRAs as it is a more transparent option. Transparency in this regard is important, as Australian health care consumers must have

confidence that public health and safety will not be undermined if the Australian NRA utilises assessment reports from comparable overseas NRAs. Being able to see the criteria against which NRAs are assessed may help to provide such reassurance. It also provides the opportunity to

The selection of comparable overseas regulators should be based on an assessment against a transparent set of criteria.

differentiate comparable overseas NRAs for different types of medicines. For example, some stakeholders argued that the FDA might not be an appropriate ‘comparable overseas NRA’ for the purposes of biosimilars at this time because of its limited experience with these products. Transparent criteria against which overseas NRAs are assessed for the purpose of Pathway Two applications should be developed in consultation with consumers, health professionals and industry.

4.3.3.2  Availability of un-redacted evaluation reports

Access to un-redacted evaluation reports is critical so that the Australian NRA can obtain a full picture of the efficacy, safety and quality of the medicine. This will inform the delegate’s decision to register/not register and also provide the basis of advice to the sponsor, prescribers and the Australian public about the decision. It is also essential in terms of post-market monitoring going forward, including risk management.

It is proposed that it would be the responsibility of the applicant to provide the Australian NRA with the full un-redacted evaluation report(s) prepared by the overseas NRA. As such, to utilise Pathway Two the Australian sponsor would need to be the same commercial/legal entity as the sponsor in the overseas jurisdiction or have a significant contractual arrangement with the overseas sponsor, in order to obtain access to the report.

If it proves difficult for sponsors to access un-redacted evaluation reports from overseas NRAs, the Australian Government might consider pursuing access through diplomatic channels. For example, via the development of Memoranda of Understanding (MOU) with relevant countries that provide for the exchange of un-redacted evaluation reports in circumstances where this is agreed by the sponsor. Such negotiations would need to consider how the un-redacted evaluation report was to be used, noting that the Australian NRA would seek to utilise aspects of the report in its Australian Public Assessment Report (AusPAR) for the medicine. AusPARs are published for all NCEs and it is required to provide detail on efficacy, safety and quality issues so that health care professionals and consumers can take these into account when using particular new medicines for individual patients.

4.3.3.3  Enhanced post-market monitoring of medicines

The lifecycle of a medicine has traditionally been divided by regulators into two stages: pre-market and post-market. During the pre-market stage, access to the medicine is generally limited to patients who are allocated to the treatment arm of a clinical trial. Once the medicine is registered this changes abruptly, as access is expanded ‘from a relatively

small number of highly selected trial subjects to millions of real-world patients who might not fit treatment eligibility requirements as specified on the label.’²¹ This poses challenges for regulators charged with protecting public health and safety. As noted by Iedema et. al.:

The risk of a drug in ‘real world’ use is often underestimated in clinical trials, as they are often designed to demonstrate efficacy rather than test safety. The trials generally study a highly selected patient group – with a long list of exclusions designed to mitigate risk – and the patients are intensively followed in a manner not typically feasible in routine practice. The true risk of a drug is generally unclear until there is considerable postmarketing experience.²²

As such, clinical trials provide information about many of the possible adverse effects of a medicine, but they do not detect all possible adverse effects because they generally do not:

·           Continue for long enough to detect adverse events that may develop over a long period of time.

·           Include enough patients to detect adverse events that occur with low incidence.

·           Include all of the different types of people who might eventually use the medicine and who might be more susceptible to some adverse events, such as older people, children, pregnant women, or people with comorbidities.²³

As such, it is important for effective post-market monitoring to occur in order to identify possible issues with safety or efficacy that may emerge when the medicine is used in a real world setting. A consistent theme in the Panel’s discussions with stakeholders and in submissions to the Review was that any change in oversight of pre-market assessments by the Australian NRA should be counter-balanced by enhanced post-market monitoring so that emerging problems are detected and addressed promptly. This was considered to be even more important where medicines are approved under expedited approval processes that may rely on more limited clinical data than is traditionally required.

The Panel concurs with this view. The pre-market assessment of medicines for safety, quality and efficacy is essential to protect public health and safety. It would be remiss to make significant changes to the process for such assessments without putting in place safeguards to monitor and detect any adverse outcomes that may result. As such, the Panel recommends that the introduction of Pathways Two and Three go hand-in-hand with enhanced post-market monitoring. As enhanced post-market monitoring is applicable  across both the medicines and medical devices frameworks, it is discussed in detail in Chapter Seven.

4.3.3.4  Implementation Strategy

If properly designed and implemented, Pathway Two may be an attractive option, particularly for smaller pharmaceutical companies who have limited capacity to develop, submit and service applications for registration to multiple markets at the same time. As

outlined in Chapter Three, a study by the CIRS of 146 new chemical entities that were launched between 2005 and 2010 found that while ‘top’ companies often lodge simultaneous applications with a number of regulators, ‘non-top’ companies staged the rollout of their product into different markets.^iv The CIRS concluded that this was because ‘companies with large R & D budgets are more likely to have the resources to undertake the submission of dossiers and to support their review in multiple jurisdictions’.²⁴

The analysis found that of the 146 new chemical entities launched between 2005 and 2010, only around half (53 per cent) were registered in Australia by 31 December 2012. This represented 80 per cent of the medicines developed by ‘top companies’ and only 32 per cent of those developed by non-top companies. Designing Pathway Two in a manner that provides for more timely assessment, and is both less costly and less resource intensive for sponsors, may encourage these smaller manufacturers to bring their products to the Australian market more quickly.

New Chemical Entities

The Panel proposes that, in order to utilise Pathway Two for a new chemical entity the product sponsor would be required to submit to the Australian NRA:

1.  A full application in CTD format including Module 1 of the CTD describing the administrative information and prescribing information (for example, the proposed product information and labelling) for Australia. Modules 2 to 5 would reflect those submitted to the overseas NRA, reducing the need to produce a different set of documents for the Australian market.

2.  An un-redacted copy of all evaluation reports, in English, completed by the comparable overseas NRA.

3.  Certification/evidence that:

A.  The medicine is identical to the one approved by the trusted overseas regulator (i.e. same dosage form, strength, formulation and indications); and

B.  The medicine will be manufactured by the same manufacturer as the medicine approved by the overseas regulator or, if not, that it will be manufactured at a  plant that has received applicable GMP certification from the Australian NRA (or from a comparable overseas NRA with whom the Australian NRA has co- recognition); and

C.  The manufacturing process to produce the medicine will be identical to that assessed by the comparable overseas regulator for the overseas product; and

D. 

iv ‘Top’ companies were defined as those with a research and development spend of greater than $US 3 billion in 2010.

4.  Details of the outcomes of the application in all jurisdictions where it has been submitted (this is a current requirement).

5.  Appropriate certifications and/or authentication of reports, and acknowledgement of penalties for providing false or misleading information.

Evaluation by the NRA

The Australian NRA would evaluate the application in an abbreviated manner to:

1.        Verify that the certifications outlined at 3A to 3D above are correct.

2.        Ensure that the medicine is fit for the Australian population and conditions, taking into account factors such as demographics, climatic conditions, disease epidemiology, and clinical practice.

3.        Verify that the post-market risk management tools proposed for the medicine in Australia are appropriate considering Australia’s specific clinical environment.

4.        Ensure proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

Based on the overseas evaluation report and the above assessment, the Australian NRA would make a decision whether or not to recommend the registration of the medicine in the ARTG. If registered, the NRA would regulate the medicine in the same way as any other medicine, e.g. the sponsor would still need to seek approval from the Australian NRA for later variations to the medicine. The Panel believes that this abbreviated assessment should generally be achievable within 60 working days, once complete and correct documentation is received from the sponsor.

Where a medicine does not meet all of the requirements outlined in 3A to 3D above, this should not preclude it from utilising Pathway Two, but the extent of evaluation that would need to be conducted, and thus the time taken, by the Australian NRA in these circumstances would be greater. For example, where the product is identical but the sponsor is seeking registration for a different indication, the Australian NRA could rely on relevant material, for example pre-clinical, manufacturing, and release specification data, but could undertake its own assessment of clinical efficacy. In these circumstances a longer assessment timeframe would be necessary, depending on the extent of evaluation required by the Australian NRA. An indicative algorithm for the proposed application pathways for non-expedited assessment of new chemical entities is at Figure 8.

Recommendation Six

The Panel recommends that in circumstances where a sponsor seeks registration of a new chemical entity in Australia via Pathway Two and has submitted all necessary materials, including an un-redacted evaluation report from a comparable overseas NRA, to the Australian NRA:

1.         The Australian NRA makes a recommendation regarding registration of the new chemical entity once it has satisfied itself that:

A.  The new chemical entity is identical in dosage form, strength, formulation and indications; and

B.  The new chemical entity will be manufactured at a plant that has received GMP certification from the Australian NRA (or from a comparable overseas NRA with whom the Australian NRA has co-recognition); and

C.  The manufacturing process to produce the new chemical entity will be identical to that assessed by the comparable overseas NRA for the overseas product; and

D.  There are no specific issues regarding applicability of the submitted data to the Australian context that need to be examined; and

E.  Proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

2.         Where the new chemical entity seeking registration in Australia does not meet conditions 1A to 1D above, the Australian NRA undertakes an assessment of the extent to which the differences have the potential to impact the quality, safety or efficacy of the product.

A.  If the differences are assessed to have minimal impact on product quality, safety or efficacy, the Australian NRA should satisfy itself that the proposed product labelling, Product Information, and Consumer Medicine Information is appropriate and consistent with Australian requirements before making a recommendation regarding registration of the new chemical entity in the ARTG.

B.  Where differences between the new chemical entity seeking registration in Australia and that approved by the comparable overseas NRA have the potential to impact product quality, safety or efficacy, before making a recommendation regarding registration of the new chemical entity in the ARTG, the Australian NRA should:

I.   Undertake an assessment of the application for registration to the extent necessary to satisfy itself that any potential impact of the differences on quality, safety or efficacy have been addressed and/or taken into consideration in assessing risk and benefit; and

II.   Assess whether the proposed product labelling, Product Information, and Consumer Medicine Information are appropriate and consistent with Australian requirements.

Figure 8: Non-expedited application pathways to registration of a new chemical entity

Generics and Biosimilars

As outlined in section 4.3.2, Pathway Two should also be available for registration of new generic medicines and biosimilars in the ARTG. The Panel proposes that, in order to utilise Pathway Two for a generic medicine or biosimilar, the product sponsor would be required to submit to the Australian NRA:

1.  A full application in CTD format including Module 1 of the CTD describing the administrative information and prescribing information (for example, the proposed product information and labelling) for Australia. Modules 2 to 5 would reflect those submitted to the overseas NRA, reducing the need to produce a different set of documents for the Australian market.

2.  An un-redacted copy of all evaluation reports completed by the comparable overseas NRA.

3.  Certification/evidence that:

A.      The generic medicine or biosimilar is identical in dosage form, strength and formulation to the product approved by the comparable overseas NRA; and

B.      The generic medicine or biosimilar will be manufactured at a plant that has received GMP certification from the Australian NRA (or from a comparable overseas regulator with whom the Australian authority has co-recognition); and

C.      The manufacturing process to produce the generic medicine or biosimilar will be identical to that assessed by the comparable overseas NRA for the overseas product; and

D.     If the product is a generic medicine – the reference product used by the comparable overseas NRA when assessing bioequivalence was identical to, or interchangeable with, the Australian reference product; or

E.      If the product is a biosimilar – the overseas product and the Australian reference product were the same.

4.  Details of the outcomes of the application in all jurisdictions where it has been submitted.

5.  Appropriate certifications and/or authentication of reports, and acknowledgement of penalties for providing false or misleading information.

The Australian NRA would evaluate the application in an abbreviated manner to:

1.                  Verify that the certifications/evidence outlined at 3A to 3D above are correct (if the product is a generic) or that the certifications/evidence outlined at 3A to 3C and 3E are correct (if the product is a biosimilar).

2.                  Ensure proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

Based on the overseas evaluation report and the above assessment, the Australian NRA would make a recommendation whether or not to register the medicine in the ARTG. If registered, the NRA would regulate the medicine in the same way as any other medicine,

e.g.    the sponsor would still need to seek approval from the Australian NRA for later variations to the medicine. The Panel believes that this abbreviated assessment should generally be achievable within 60 working days, once complete and correct documentation is received from the sponsor.

Where a generic medicine or biosimilar does not meet all of the requirements outlined in 3A to D (generic) or 3A to C and 3E (biosimilar), this should not preclude it from utilising Pathway Two, but the extent of evaluation that would need to be conducted by the Australian NRA, and thus the time taken, in these circumstances would be greater. An indicative algorithm for the proposed Pathway Two for generic medicines and biosimilars is at Figure 9.

Recommendation Seven

The Panel recommends that in circumstances where a sponsor seeks registration of a generic medicine or biosimilar in Australia via Pathway Two and has submitted all necessary materials, including an un-redacted evaluation report from a comparable overseas NRA, to the Australian NRA:

1.         The Australian NRA makes a recommendation regarding registration of the generic medicine or biosimilar once it has satisfied itself that:

A.                 The generic medicine or biosimilar is identical in dosage form, strength, and formulation to the product approved by the comparable overseas NRA; and

B.                 The generic medicine or biosimilar will be manufactured at a plant that has received GMP certification from the Australian NRA (or from a comparable overseas NRA with whom the Australian authority has co-recognition); and

C.                 The manufacturing process to produce the generic medicine or biosimilar will  be identical to that assessed by the comparable overseas NRA for the overseas product; and

D.                If the product is a generic medicine - the reference product used by the comparable overseas NRA when assessing bioequivalence was identical to, or interchangeable with, the Australian reference product; or

E.                  If the product is a biosimilar - the overseas reference product and the Australian reference product were the same; and

F.                   Proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

2.         Where the generic medicine seeking registration in Australia does not meet conditions 1A to 1D above, the Australian NRA undertakes an assessment of the extent to which the differences have the potential to impact the quality, safety or efficacy of the product.

A.                 If the differences are assessed to have minimal impact on product quality, safety or efficacy, the Australian NRA should satisfy itself that the proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements before making a recommendation regarding registration of the generic medicine in the ARTG.

B.                 Where differences between the generic medicine seeking registration in Australia and that approved by the comparable overseas NRA have the  potential to impact product quality, safety or efficacy, before making a recommendation regarding registration of the generic medicine in the ARTG, the Australian NRA should:

I.                              Undertake an assessment of the application for registration to the extent necessary to satisfy itself that any potential impact of the differences on quality, safety or efficacy have been addressed; and

II.                               Assess whether the proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

3.         Where the biosimilar seeking registration in Australia does not meet conditions 1A to 1C and 1E above, the Australian NRA undertakes an assessment of the extent to which the differences have the potential to impact the quality, safety or efficacy of the product.

A.                 If the differences are assessed to have minimal impact on product quality, safety or efficacy, the Australian NRA should satisfy itself that the proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements before making a recommendation regarding registration of the biosimilar in the ARTG.

B.                 Where differences between the biosimilar seeking registration in Australia and that approved by the comparable overseas NRA have the potential to impact product quality, safety or efficacy, before making a recommendation regarding registration of the biosimilar in the ARTG, the Australian NRA should:

I.                              Undertake an assessment of the application for registration to the extent necessary to satisfy itself that any potential impact of the differences on quality, safety or efficacy have been addressed; and

II.                               Assess whether the proposed product labelling, Product Information and Consumer Medicine Information are appropriate and consistent with Australian requirements.

Figure 9: Application pathways for registration of a generic medicine or biosimilar