International regulatory news in brief

This post covers international regulatory news in brief. It will be updated on an ad hoc basis.

To ease navigation, tabs have now been added for each region.

Latest updated section(s): EU (Finland), Oceania (Australia)

8 September
UK MHRA update on managing clinical trials during COVID-19

The UK MHRA has updated its guidance on managing clinical trials during the COVID-19 pandemic. Updated comprehensive guidance has been published on remote monitoring for trials.

Source: MHRA website

2 September
UK annual accountability review minutes 2021 – Information on the ILAP pathway

The minutes for the above have been published. On innovation, Dr June Raine (Chief Exec. MHRA)mentioned the success of the Innovative Licensing and Access Pathway (ILAP), whereby the MHRA has recently awarded an ‘Innovation Passport’ for a treatment for sickle cell disease, a rare blood disorder. Dr Raine highlighted that ILAP may be extended to include more products other than medicines.

Source: MHRA website

1 September 2021
Israel joins project Orbis

Israel’s Division of Medical Technologies, Information, and Research has joined the United States Food and Drug Administration (FDA) in its Project Orbis initiative, according to the Israeli Ministry of Health.

Project Orbis is a collaborative initiative of the FDA’s Oncology Center of Excellence (OCE) which allows for concurrent submission and review of oncology drugs among the regulatory agencies of the US, Switzerland, Australia, Canada, Singapore, and, most recently Brazil and the United Kingdom.

For the purpose of obtaining consent to exchanging information, Swissmedic has amended the relevant sections of the forms New authorisation of human medicinal products HMV4 (section 7.9) and Variations and authorisation extensions HMV4 (section 6.10) have been amended accordingly.

The revised guidance document Project Orbis HMV4 is available here.




17 September

Piloting of the EU Regulation on Clinical Trials to end very soon in Finland

Fimea and TUKIJA started in November 2020 the piloting of the new clinical trials assessment process in accordance with the EU Regulation.

Now the project has reached the final stage. The deadline for submission of applications for new clinical trials and substantial modifications in the pilot project is 27 September 2021.

Source: Fimea website

10 September
HPRA consults on proposed clinical trial fees for 2022

The HPRA and NREC are proposing to increase/restructure a number of clinical trial fees to reflect new responsibilities under the new legislation. The HPRA is seeking comments on the proposal for clinical trial fees for 2022.

Start Date of the consultation: 13 September 2021

Closing date of consultation: 8 October 2021

The consultation is available on the HPRA website here. You can send any comments or questions on these proposals by e-mail to

Source: HPRA website

2 September
New version 3 of the national directive available to supplement the European guidelines for the management of clinical trials during the coronavirus pandemic.

A new version of the national directive is available to supplement the European guidelines (v3) for the management of clinical trials during the coronavirus pandemic.

The new version of the directive is the result of a collaboration between the FAMHP, the Clinical Trial College, the Belgian Association of Research Ethics Committees (BAREC), and several research centres. The national directive applies from the moment of its publication and supplements the European guidelines.

These new guidelines should help sponsors of clinical trials manage:
•    clinical trials for the prevention or treatment of COVID-19;
•    clinical trials underway in Belgium.

The national directive also provides answers to frequently asked questions and will be updated depending on how the pandemic further develops.

Source: FAHMP website

European Medicines Agency
ECDC and EMA highlight suggest no urgent need for the administration of booster doses of vaccines to fully vaccinated individuals 

Aaccording to a technical report issued yesterday by the European Centre for Disease Prevention and Control (ECDC), based on current evidence, there is no urgent need for the administration of booster doses of vaccines to fully vaccinated individuals in the general population,. The report also notes that additional doses should already be considered for people with severely weakened immune systems as part of their primary vaccination.

Evidence on vaccine effectiveness and duration of protection shows that all vaccines authorised in the EU/EEA are currently highly protective against COVID-19-related hospitalisation, severe disease and death, while about one out of three adults in the EU/EEA over 18 years is still currently not fully vaccinated. In this situation, the priority now should be to vaccinate all those eligible individuals who have not yet completed their recommended vaccination course.

To complement vaccination efforts, it is also crucial to continue applying measures such as physical distancing, hand and respiratory hygiene, and using face masks where needed, in particular in high-risk settings such as long-term care facilities or hospital wards with patients at risk of severe COVID-19.

Source: European Medicines Agency

6 September
Malaysia publishes two new pharmacovigilance guidelines

Malaysia has published the following two pharmacovigilance guidelines:

Malaysian Guidelines on Good Pharmacovigilance Practices (GVP) for Product Registration Holders

This guideline, which is intended for Product Registration Holders, outlines the requirements and procedures of Good Pharmacovigilance Practices (GVP) activities including but not limited to the submission of ADR and adverse event following immunisation (AEFI) reports, and the submission of information regarding product safety to the DCA. This guideline has also included one (1) new part (Part 6) related to Pharmacovigilance System Master File.

The chapter on “Submission of ADR Reports by Healthcare Professionals” has been taken out and issued as a separate guidance.

Adverse Drug Reaction (ADR) / Adverse Event Following Immunisation (AEFI) Reporting Manual for Healthcare Providers

This manual outlines the requirements and procedures of reporting for ADR as well as reporting and investigation of AEFI. It has also included the new causality assessment for AEFI.

20 September
TGA publishes guidance on software for use with COVID-19 rapid antigen self-tests

The TGA has published guidance TGA publishes guidance on software for use with COVID-19 rapid antigen self-tests.

Software regulated by the TGA

According to the guidance, if your software analyses or enables interpretation of the test sample or results in any way (whether by the user or another person), it is regulated as a medical device and must be included in the ARTG. Software that analyses/interprets results from COVID-19 rapid antigen self-tests would be regulated as a Class 3 in vitro diagnostic (IVD) medical device analysis software and require separate inclusion in the ARTG.

Software that allows a user to combine their test result with other symptoms to provide an
indication or likelihood of having COVID would also be regulated as an IVD medical device.

Software not regulated by the TGA

Software that is used simply for registration, recording of results and tracking, or for
generation or update of a digital health record, is not considered a medical device and so would not be regulated by the TGA.

Software that solely enables uploading of results to a database for the purpose of facilitating contact tracing or follow-up testing would not be regulated by the TGA.

Source: TGA website

17 September
Outcome of Proposed improvements to the Therapeutic Goods Advertising Code

Between Friday 7 May 2021 and Friday 18 June 2021, the TGA conducted a public consultation to seek feedback on options to improve the Therapeutic Goods Advertising Code (No.2) 2018 (the Code).

Here, you can view the responses to the consultation.

In response to this feedback, The TGA has decided to re-write the Code using a simplified structure and plainer language. They will also ensure the guidance on the Code is more accessible and user-friendly.

Source: TGA website

15 September 2021
Conformity assessment certificates, changes to requirements for certain medical devices

On 23 July 2021 the Government repealed Regulation 4.1 and amended Regulation 5.3 of the Therapeutic Goods (Medical Devices) Regulations 2020.

This means that:

  • since 28 July 2021, medical devices that contain medicines or materials of animal, microbial, recombinant or human origin; and Class 4 in vitro diagnostic (IVD) medical devices no longer require mandatory TGA conformity assessment certification.
  • now, sponsors can provide conformity assessment documents issued by notified bodies designated by a member state of the European Union to support an application for inclusion in the ARTG.

Note that Australia has some different regulatory requirements to Europe e.g. biologicals and therefore, the amendment to Regulation 5.3 provides for the TGA to audit applications to ensure the information provided meets the Australian regulatory requirements. This ensures that safety and performance is demonstrated prior to approving the device for supply in Australia.

Changes to application audit requirements for medical devices

Due to the changes detailed above, selecting applications for audit allows the TGA to review compliance with Australian-specific regulatory requirements, including ensuring safety and performance can be demonstrated, while also recognising the enhanced standards contained in these EU regulations.

Selecting applications for audit allows the TGA to review compliance with Australian-specific regulatory requirements, including ensuring safety and performance can be demonstrated, while also recognising the enhanced standards contained in these EU regulations (i.e. Medical Devices Regulation (EU) 2017/745 and In Vitro Diagnostics Regulation (EU) 2017/746))

For devices supported by older certificates issued under several earlier EU Directives, the TGA will conduct in-depth audits for all those applications that rely on conformity assessment documents issued under the following EU Directives:

  • 93/42/EC (Medical devices)
  • 90/385/EEC (Active implantable medical devices)
  • 98/79/EC (In vitro diagnostic medical devices)

This is in line with the way the TGA undertakes a risk-based assessments of applications for other high-risk medical devices.

Source: TGA website

13 September
The claim ‘TGA approved’ must not be used in advertising

The TGA states that inclusion of a therapeutic good in the ARTG is not an endorsement of that good .

  • Advertisers must not use terms such as ‘TGA approved’ or ‘TGA registered’ in therapeutic goods advertising, including on labels or packaging.
  • The use of a TGA logo or Commonwealth Coat of Arms is also prohibited.
  • However, advertisers can include details of the product’s ARTG number (and this number is mandatory on medicine labels and packaging). For certain medicines, a ‘TGA assessed claim’ can also be used in advertising.

Source: TGA website

10 September
TGA Highlights and achievements report: international engagement strategy 2016-2020:

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.

From the report, it seems that the TGA with approximately 750 employees, punches well above its weight for achievements. The report is useful for anyone who is unaware of/wants to familiarise themselves with the full breadth of international activities and collaborations that the TGA engages in. Information on a small number of these is provided below:

  • Indo-Pacific Regulatory Strengthening Program (Launched in 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.
  • 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. As a result, the TGA will continue various activities including contributing to the strengthening of regulatory capacity of authorities in the Western Pacific Region and other regions through the regional alliance frameworks associated with vaccines & biological medicines.
  • 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
  • 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.
  • 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 body
    • The Access Generics Work-Sharing Program has to date approved three generic medicines, including Everolimus-Teva, Posaconazole Sandoz and Fulvestrant Sandoz

Source: TGA Website

7 September
FDA launches novel excipient review pilot program

The Center for Drug Evaluation and Research (CDER) has launched the voluntary Novel Excipient Review Pilot Program which is intended to allow excipient manufacturers to obtain FDA review of certain novel excipients prior to their use in drug formulations. This Pilot Program will foster development of excipients that may be useful in scenarios in which excipient manufacturers and drug developers have cited difficulty in using existing excipients.

The Pilot Program will initially be available for novel excipients that

  1. have not been previously used in FDA-approved drug products, and
  2. do not have an established use in food. 

It will consist of two stages. The first stage is an initial proposal stage for excipient manufacturers to provide a high-level overview of their novel excipient. CDER intends to accept approximately four initial proposals but will consider accepting more proposals as resources allow. Excipient manufacturers whose initial proposals are accepted would then enter the second stage, during which they would provide a full data package consisting of toxicology and quality data. 

Source: FDA website

1 September
FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions

Based on a completed U.S. Food and Drug Administration (FDA) review of a large randomised safety clinical trial, the FDA has concluded that there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR (tofacitinib). This trial compared Xeljanz with another type of medicine used to treat arthritis called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The trial’s final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz. A prior Drug Safety Communication based upon earlier results from this trial, reported an increased risk of blood clots and death only seen at the higher dose.

FDA are requiring new and updated warnings for two other arthritis medicines in the same drug class as Xeljanz, called Janus kinase (JAK) inhibitors, Olumiant (baricitinib) and Rinvoq (upadacitinib). Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action withXeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.

Two other JAK inhibitors, Jakafi (ruxolitinib) and Inrebic (fedratinib), are not indicated for the treatment of arthritis and other inflammatory conditions and so are not a part of the updates being required to the prescribing information for Xeljanz, Xeljanz XR, Olumiant, and Rinvoq. Jakafi and Inrebic are used to treat blood disorders and require different updates to their prescribing information. If FDA becomes aware of any additional safety information or data that warrants updates to the prescribing information for these medicines, they may take further action and will alert the public.

Further information associated with this update is available here.

Source: FDA website

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