Introduction

The Therapeutic Goods Administration (TGA) within the Department of Health, collaborates internationally on the regulation of medicines and medical devices. TGA also contributes significantly to strengthening regulatory capabilities in our region.

The TGA International Engagement Strategy 2016-2020 outlined TGA’s priorities for regulatory programs and policies through collaborations with other national regulators and international organisations. Progress against the Strategy was informed by Annual Operations Plans. This report highlights some of the achievements between 2016-2020.

This report highlights TGA’s achievements under its International Engagement Strategy 2016-2020. TGA’s strategic priorities in international engagement over the next four years are outlined in the TGA International Engagement Strategy 2021-2025 which builds upon the abovementioned work. The new strategy continues to highlight TGA’s commitment to building a regulatory framework that is more globally aligned and responsive to the latest regulatory science developments to meet the needs of Australians. The TGA will continue to contribute to regulatory strengthening in our region and provide a leadership role in important international activities.

Goal 1. Contribute to public health and safety through regulation

The TGA committed to support and engage with the World Health Organisation (WHO) and other regulators, work with other regulators in our region to build capacity, and to participate in international regulatory fora to improve public health and safety.

Indo-Pacific Regulatory Strengthening Program

The Indo-Pacific Regulatory Strengthening Program (RSP) was officially launched in October 2018. Through this program, the TGA is leading technical engagement with counterpart National Regulatory Authorities (NRAs) in Cambodia, Indonesia, Myanmar, Lao PDR, Papua New Guinea and Vietnam as well as working with Thailand as a partner country.

The RSP’s goal is to strengthen health security through improved access to high quality, safe and effective products for the diagnosis, treatment, and prevention of infectious disease threats in the Indo-Pacific region. This goal is being delivered through two inter-related components: strengthening the capability of country NRAs to ensure timely access to safe, high quality and effective medical products; and ensuring stakeholder coordination to promote regional collaboration on regulatory practice. Countries in the RSP have varied priorities, experience and expertise. The TGA is implementing customised packages of assistance based on mutually agreed workplans that have been developed from country specific WHO Institutional Development Plans and individual regulator priorities.

A Program Management Unit supported by a TGA Program Manager has been established in Singapore. The Unit facilitates the development of strong collaboration between countries in the region as well as partner organisations.

With the impact of the COVID-19 pandemic, the RSP continued to provide regulatory strengthening support to countries. This support has been expanded to assist national regulators with their regulatory response to the pandemic as well as preparedness for regulation of treatments and/or vaccines as they become available.

Pacific Medicines Testing Program

The Pacific Medicines Testing Program began as a pilot program from September 2017 to June 2021. This joint program between the Department of Foreign Affairs and Trade (DFAT) and the Department of Health (facilitated by the TGA) was established to support quality assurance of medicines across the Pacific region and focused on laboratory testing of medicines for non-communicable diseases and antibiotics. Twelve Pacific Island countries (PICs) participated in the pilot Program including the Federated States of Micronesia, Fiji, Kiribati, Nauru, Palau, Papua New Guinea, the Republic of the Marshall Islands, Samoa, the Solomon Islands, Timor Leste, Tonga, Tuvalu and Vanuatu.

Over the four-year pilot Program, the TGA tested 223 therapeutic goods for participating PICs which supported Pacific Island governments to make decisions about upgrading medical storage facilities, recalling medicines, changing suppliers, and notifying other partner governments about product issues. It has also improved awareness of therapeutic goods safety issues and the broader need for regional therapeutic goods regulation processes. It has supported the development of strong people-to-people links, enhanced regional security, and generated significant good will. The TGA also played an important role as an intermediary between Chief Pharmacists and the WHO in discussions on the development of a sub-regional pharmaceutical regulatory platform.

Due to the success of the pilot Program, DFAT and the TGA have signed an agreement for Phase Two of the program which commenced on 1 July 2021. PMTP Phase Two will run for four years through to 30 June 2025 and the twelve PICs involved in the pilot Program as well as Timor-Leste have been invited to participate. Phase Two of the PMTP will remain focussed on medicines for non-communicable diseases but also has a broadened scope to include testing of therapeutic goods used in response to the COVID−19 pandemic. On request, the TGA may also test therapeutic goods that are suspected to be substandard, or that have been associated with an adverse event, problem or complaint.

WHO Collaborating Centres

The TGA Laboratories successfully gained redesignation for the WHO Collaborating Centres for Drug Quality Assurance and for Quality Assurance of Vaccines and other Biologicals in 2018 for the period 2019-2022. The TGA will continue to:

• contribute to strengthening regulatory capacity of authorities in the Western Pacific Region and other regions through the regional alliance frameworks associated with vaccines & biological medicines
• in collaboration with WHO, provide training of laboratory personnel in the validation and application of analytical procedures in the quality assurance of medicines and support countries where there is no direct access to local laboratory services
• provide input to the development of WHO’s international measurement standards and reference reagents for vaccines and biologicals.

Regulator capacity development

The TGA provided training programs for several national regulators, including from Saudi Arabia, Botswana and Sri Lanka. 

The training for the Saudi Food & Drug Authority included the TGA’s medicines regulatory framework, assessment of biological medicines, cell and tissue therapies, pre-clinical safety assessment and post-market monitoring.

A delegation from the Botswana Medicines Regulatory Authority (BMRA) visited the TGA to benchmark the BMRA’s own complementary health products regulatory framework against the TGA's, and to understand the TGA’s regulations for medicinal cannabis.

The complementary medicines training program for the Sri Lanka National Medicines Regulatory Authority included regulation, quality requirements and standards, the listing process, borderline products and the role of adverse event reporting and advertising.

Participation and leadership in international regulatory organisations

The TGA regularly participates and contributes to major international forums for development of regulatory guidelines and harmonisation, including as Vice-Chair of ICMRA and as a member and Chair of a range of programs, such as the vaccines pharmacovigilance program.

The topics covered for medicines and devices included work-sharing for market authorisations, products under investigation, shortages, manufacturing quality guidelines, pharmacovigilance systems, and counterfeit drugs and fraudulent claims.

The forums include:

• The International Coalition of Medicines Regulatory Authorities (ICMRA)
• The Australia-Canada-Singapore-Switzerland-United Kingdom Consortium (Access)
• The World Health Organisation (WHO)
• International Medical Device Regulators Forum (IMDRF)
• Medical Device Single Audit Program (MDSAP)
• The International Council for the Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)
• International Pharmaceutical Regulators Programme (IPRP)
• Pharmaceutical Inspections Cooperation Scheme (PIC/S).

Goal 2. Work with others to improve the regulatory system

The TGA’s commitment during the 2016-2020 period was to increase flexibility in pre-market assessment and market authorisation by operationalising work-sharing of medicines under Access and medical devices through MDSAP. The development of a more comprehensive post-market monitoring scheme for medicines and medical devices was another aim.

Medical Device Single Audit Program

TGA continues to support expansion of the MDSAP through active involvement in the Regulatory Authority Council (RAC) and Subject Matter Expert (SME) Group. TGA representatives participate in the MDSAP RAC. Through the RAC, the TGA has:

• contributed to the expansion of the MDSAP Affiliate member program. Affiliate members now include regulators from Argentina (ANMAT), South Korea (KFDA) and Singapore (HSA). In addition, the UK MHRA has been accepted as an Official Observer, joining the EU and WHO
• maintained the Auditing Organisation assessment and recognition program through the pandemic, including processing applications from new Auditing Organisations
• provided guidance to the Auditing Organisations on the use of remote audits and other interim audit methods to maintain oversight and certification to medical device manufacturers during the pandemic and associated travel restrictions
• determined options to transition from the Pan American Health Organisation hosted MDSAP Regulatory Exchange Program system to an alternative Regulatory Authority hosted system
• we have contributed to the development and improvement of International Medical Device Regulator Forum (IMDRF) guidance documents.

Staff participated in a virtual MDSAP Forum in December 2020. The TGA provided an update on regulatory changes and contributed to training sessions to improve the quality of audit reports and nonconformity reporting.

Project Orbis

The TGA, in collaboration with Health Canada, Singapore’s Health Sciences Authority, Swissmedic, the UK’s MHRA and Brazil’s ANVISA, worked with the US FDA through this program for concurrent submission and review of oncology drugs.

The Project Orbis work-sharing evaluations approved 13 products by December 2020, and there are 20 Orbis collaboration applications in the pipeline at May 2021. The collaborations used the framework established by the FDA’s Oncology Center of Excellence for the accelerated approval of oncology drugs, including:

• Lenvatinib in combination with Pembrolizumab for the treatment of patients with an advanced endometrial carcinoma. Endometrial cancer is a disease in which cancer cells form in the tissues of the inner lining of the uterus. Endometrial cancer is the most common cancer of the female genital tract
• Acalabrutinib for the treatment of chronic lymphocytic leukaemia and small lymphocytic leukaemia.

Access Consortium

The Access Consortium is a collaborative initiative between five national regulatory authorities, including Australia's TGA, Health Canada, Singapore's Health Sciences Authority, the Swiss Agency for Therapeutic Products (Swissmedic) and was joined by the UK’s Medicines and Healthcare Products Regulatory Agency in October 2020.

The purpose of the consortium is to build synergies and share knowledge amongst the regulatory authorities thereby enhancing efficiency of regulatory systems. Each regulator maintains independent decision-making. Market authorisation or refusal of market authorisation by one regulator will not affect the decision or the timing of the decision by the other participating regulators.

Highlights of the Access Consortium include:

• The Access New Active Substance Work-Sharing Initiative successfully approved eight new medicines. These include new medicines for targeted treatments for a range of cancers, including types of prostrate, blood, ovarian and breast cancers, and for certain heart conditions with weakened heart muscles which make it difficult for the heart to pump blood throughout the bod
• The Access Generics Work-Sharing Program has to date approved three generic medicines, including Everolimus-Teva, Posaconazole Sandoz and Fulvestrant Sandoz
• The Access Complementary Health Products Working Group (CHPWG) developed joint guidance for the safety evaluation of ingredients for use in complementary health products. The CHPWG also shared safety information and conducted numerous joint safety assessments and peer reviews of ingredient safety assessments of mutual interest during this period and developed a joint efficacy evaluation template and guidance for complementary health products. The work of the CHPWG enabled the TGA to publish a list of recognised comparable overseas bodies (COB) for complementary medicines with the goal of reducing duplicating evaluations and to shorten evaluation timeframes.

Post market monitoring activities

The TGA participates in the ongoing information sharing of pharmacovigilance activities with international regulators to strengthen TGA’s regulatory intelligence with respect to all medicines, particularly provisionally approved medicines and biological medicines. International engagement includes regular contact with FDA (USA), Health Canada (Canada), HSA (Singapore), Medsafe (NZ), SwissMedic (Switzerland) and MHRA (UK) as well as the International Society of Pharmacovigilance and the WHO Representatives of National Pharmacovigilance Centres.

From 2016-2020, TGA has published 420 safety alerts and four safety reviews on its website. To minimise the harm caused by opioid prescription medicines to Australians each year, several regulatory changes were introduced. The changes reflect over four years of work and will ensure the safe and effective prescribing and use of opioids while maintaining access for patients who need them.

The TGA has been collaborating both nationally and internationally on COVID-19 vaccination pharmacovigilance strategies. Several safety investigations have been completed and regulatory actions undertaken.

Monitoring of medicines shortages

The TGA engaged with international regulatory counterparts to identify and understand the drivers behind medicine shortages. TGA participates in the Global Regulatory Drug Shortage Working Group meetings. More recently, these meetings included a particular focus on management of shortages relating to COVID drugs of concern with the pandemic.

The TGA contributed to the US FDA's Reflection paper, ‘Improving Patient Access to Needed Medicines – What More Could Regulator’s Do?’ which was presented at ICMRA's Rome Summit in October 2019. This was to gain a better understanding of the factors contributing to medicine shortages.

The TGA continues to engage with international counterparts on a regular basis to harmonise the global approach to the issue of nitrosamine impurities in medicines through the Nitrosamine International Strategic Working Group.

Improvements for manufacture of medicines

The TGA participates in the Pharmaceutical Inspection Co-operation Scheme (PIC/S) for the development and implementation of harmonised GMP standards and quality systems for the manufacture of medicinal products.

The TGA actively participates in PIC/S working groups. Guidance developed on improving Good Manufacturing Practice (GMP) for medicines has included:

• Development of guidelines for data management and integrity, with training materials in development
• Publication on the classification of deficiencies
• New guidance on Authorised Person and Batch release for Good Manufacturing Distribution Practice
• input for the Inspector Training Curriculum Program on Active Pharmaceutical Ingredients
• Input for the ICH working group on Continuous Manufacturing of drug substances and drug products
• aide memoire on minimal manipulated human tissue and cells.

Goal 3. Participate in information sharing frameworks with international counterparts

The TGA continued engagement with international regulators and relevant organisations, participated in work sharing, utilised reliance mechanisms for medicines and medical devices, and leveraged off alerts and pharmacovigilance data from overseas regulators. International best practice and alignment with European medical devices regulation underpinned the TGA’s regulatory approach.

The TGA, using Health’s Qualtrics platform, contributed to the ICMRA Pharmacovigilance Increasing Adverse Events Reporting sub-group to develop the ‘Increasing Adverse Event Reporting (IAER) subproject: Survey report’ which compiles data from 11 ICMRA members.

The TGA surveyed members of the ICMRA Vaccines Pharmacovigilance Working Group to establish what each jurisdiction was planning in the vaccine Adverse Drug Reaction (ADR) communications area.

Active Pharmaceutical Ingredients manufacturers

The TGA participated in information sharing with international regulators to facilitate GMP inspection reliance. Cooperation with Health Canada continues to build on collaborative arrangements for GMP inspections for Active Pharmaceutical Ingredients (API) manufacturers. In addition, TGA participates in monthly meetings as part of the participation in the PIC/S Programme to rationalise international GMP Inspections of API manufacturers with Canada, Denmark, France, Ireland, Italy, Japan, UK, USA, European Medicines Agency (EMA), and the WHO.

Medical Device Reforms

The TGA made progress towards the establishment of a Unique Device Identification (UDI) database to enhance Australia's ability to trace medical devices and strengthen post-market medical device adverse event system. This included:

• working with the IMDRF WG on Adverse Event Terminology to progress harmonisation of terms relating to the event type, evaluation, patient injury and device component, and implemented into TGA’s adverse event database the six published annexes.

The TGA’s active participation in a range of IMDRF Working groups has led to increased convergence. This includes:

• Through its role with the IMDRF WG on medical device cybersecurity, TGA was the first regulatory jurisdiction to release cybersecurity guidance on total product life cycle
• Participation in the IMDRF pilot to trial the Table of Contents submission format will provide a harmonised international electronic submission structure to reduce regional divergence, reduce burden on industry, and increase efficiency of assessment bodies
• TGA published a guideline on Optimizing standards for regulatory use following a project with the IMDRF WG on how regulatory authorities recognise and use ISO and IEC standards
• Participation in the IMDRF Personalized medical devices working group to develop guidance that establishes definitions and regulatory pathways for regulatory authorities to consider in the regulation of medical devices that are intended for individual patients. TGA chaired this group throughout 2019-20 and progressed the draft guidance to publication
• Australia was the first jurisdiction to implement new regulations for personalised medical devices into law.

International collaborations to facilitate access to COVID-19 products

The TGA was a central part of Australia’s national and international response to the COVID-19 pandemic outbreak.

The TGA participated in early regulatory collaboration with other national regulators and international organisations such as the WHO and ICMRA. It also worked with sponsors and industry for faster assessment of vaccine candidates which included rolling reviews of data as they became available, and regulatory approval for vaccine supplies and local vaccine manufacture. National monitoring for COVID-19 infection was supported by priority testing, approval and compliance monitoring for diagnostic tests, medical devices such as ventilators, and personal protective equipment.

The TGA’s regulatory support for countries in the Indo-Pacific region and more widely extended to assistance with their national COVID-19 approval and vaccine safety programs. 

As a member of the Access Consortium of five national regulators and its Access Complementary Health Products Working Group, the TGA shared regulatory information on hand sanitisers to assist in responding to the increased demand during the pandemic.

In March 2020, ICMRA pivoted its work to support development and review of COVID-19 therapeutics and vaccines. Teleconferences have been regularly held to discuss medicines under investigation, regulatory authorisations, medicines shortages, quality matters, pharmacovigilance systems and counterfeit drugs and fraudulent claims. Workshops have been held on vaccines, clinical trial endpoints, and real-world evidence and observational studies.

TGA - Human Official Control Authority Batch Release Network Agreement

A Memorandum of Understanding (MoU) between the TGA and the Human Official Control Authority Batch Release Network was established on 19 November 2020. This Network includes more than 30 countries and is an important forum for the confidential exchange of quality and technical information on batches of vaccines and human biological medicines. This agreement reduces duplication of effort and recognition of batch release outcomes.

Signing of the MoU will facilitate collaboration with other Control Laboratories, an important step for the development of testing methods associated with COVID and other vaccines.

Faecal Microbial Transplant products

The TGA engaged with international experts from the USA, Europe and the UK to develop new policies and regulations for FMT products in 2020. The TGA established guidelines for the safe procedure of transferring faecal bacteria and other microbes from a healthy individual into another individual as a stool transplant. It can be more effective than antibiotics for several bacterial diseases and infections of the gut.