News Hub

by
Gerry McKiernan
Increment4
Australia

Gabrielle O'Sullivan PhD MPH (Hons)
Royal Prince Alfred Hospital Institutional Biosafety Committee (RPAH IBC)
Australia

AUSTRALIAN AND NEW ZEALAND REGULATORY UPDATES
AOTEAROA – NEW ZEALAND

Medsafe 
Clinical Trials
On 23 Aug 2024 Medsafe released for consultation changes to the Guideline on the Regulation of Therapeutic Products in New Zealand: Part 11: Clinical trials – regulatory approval and good clinical practice requirements and two new guidance documents which are proposed to be used alongside the Guideline [1]:

• Considerations for First-In-Human (FIH) and Early Phase Clinical Trials; and
•  Clinical Trial Safety Monitoring and Reporting for Investigational Products (Medicines and Medical Devices).

Updates are proposed to:

• Incorporate new or updated legislation and relevant guidance issued in New Zealand and overseas;
• Reflect changes to best practice for the design and conduct of clinical trials (eg, patient involvement in study design); and
• Provide more clarity to those involved in conducting clinical trials on their obligations.

Responses for submission close on 27 Oct 2024.

AUSTRALIA
Medtronic fined $22 million for supply of unapproved goods

In September 2024, the Federal Court of Australia has ordered Medtronic Australasia Pty Ltd (Medtronic) to pay $22 million in penalties for unlawfully supplying 16,267 units of the Infuse Bone Graft Kit between 1 September 2015 and 31 January 2020, the largest ever penalty for unlawful supply of therapeutic goods.

The Court's judgment comes after the Therapeutic Goods Administration (TGA) commenced proceedings against Medtronic in August 2021. The Court has also ordered that Medtronic pay $1 million as a contribution to the TGA’s legal costs.

This penalty is the largest ever imposed for contraventions of the Therapeutic Goods Act 1989.

Australian law generally requires that therapeutic goods are entered in the Australian Register of Therapeutic Goods (ARTG) before they can be lawfully supplied in Australia. While the Infuse Bone Graft Kit was entered in the ARTG for supply with a separately packaged spinal cage (the LT Cage), that entry in the ARTG did not allow the Kit to be supplied without the LT Cage. Medtronic unlawfully supplied the Kit without the LT Cage.

Professor Anthony Lawler, Deputy Secretary of the Department of Health and Aged Care and head of the TGA, said that “this significant penalty serves as a reminder to sponsors and others in the therapeutic goods industry to take their obligations seriously. Medicines and medical devices supplied to Australians must be assessed by the TGA for safety, efficacy, and performance in the exact way they will be supplied to patients. This protects Australians by ensuring they have access to the safest products available.” [2]

TGA Release Strategic Plan
The TGA have released their strategic plan for 2024 – 2025. The strategic plan is focused on four key areas:
Strategic objective 1 - Improve public health outcomes through best practice regulation 
Strategic objective 2 - Build trust by actively engaging with our stakeholders 
Strategic objective 3 - Promote and enforce compliance with regulatory requirements 
Strategic objective 4 - Innovate and continuously improve

The report recognises emerging technologies and innovations in cellular and gene therapies, advances in AI-driven diagnostics and decision support, and the evolution of pharmaceuticals. [3]

TGA Release Medicine Shortages Report
In July 2024, the TGA released its Medicines Shortage Report [4]. Management of Medicines Shortages has been a focus of the TGA since 2019. 
Since 2020, the TGA has improved how shortages are managed, including:

• better use of data to identify supply chain issues and anticipate potential shortages
• better public access to information about shortages
• updated guidance information for sponsors (pharmaceutical companies) to help them report and mitigate shortages
• introduced Serious Scarcity Substitution Instruments
• better coordination with other government departments
• more collaboration with clinical experts for recommendations to help conserve supply for patients with limited alternatives
• more communication with consumers
• strengthened collaboration with stakeholders in the medicine supply chain.
  While the overall number of shortages reported in Australia by medicine sponsors has remained consistent since mandatory reporting commenced, some of these shortages have had a much more significant impact on patients and health professionals than others. Examples of such high-impact shortages include the following:
• When an unexpected increase in off-label prescribing of Ozempic (semaglutide) for weight loss occurred, other GLP-1 agonists Trulicity (dulaglutide) and Mounjaro (tirzepatide) also went into shortage in a spill-over effect.
• Seven antibiotics were concurrently in shortage at one point in 2023, including all oral syrups and suspensions of cefalexin. This was particularly problematic for the paediatric and geriatric populations.
  Complicating these situations, multi-country shortages appear to be increasing, which hampers the ability of sponsors to increase supply or access overseas alternatives.

TGA request for consultation on the regulation of Artificial Intelligence
On 12 Sept 2024 the TGA released for consultation its consultation paper ‘Clarifying and strengthening the regulation of Artificial Intelligence (AI)’. The Therapeutic Goods Act is within scope of the review. [5]

The Australian Government has provided $39.9 million over 5 years for the development of policy and capability across government to support the safe and responsible adoption and use of AI technology.  This consultation paper seeks feedback on proposals identified for mitigating risks and leveraging opportunities associated with the use of AI models.

The proposed consultation has identified 10 guardrails for the use around the use AI. Responses close 13 Oct 2024.

TIWGG PIC/S Annex 2A Adoption
At the TGA Industry Working Group for GMP (TIWGG), the TGA confirmed that they are reviewing PIC/S Annex 2A – ‘Manufacture of advanced therapy medicinal products for human use’ to replace the current Australian code of good manufacturing practice for ‘human blood and blood components, human tissues and human cellular therapy products’. The TGA have indicated that the adoption of PIC/S Annex 2A may only apply to higher risk biologicals e.g. Class III and Class IV. Industry will be consulted on the adoption of Annex 2A and this adoption is expected to occur in 2025.

The TGA have also indicated that Therapeutic Goods Order No. 94 (Standard for Haematopoietic Progenitor Cells derived from Cord Blood) 2017 has commenced internal review. The current TGO 094 refers to NetCord-FACT International Standards for ‘Cord Blood Collection, Banking, and Release for Administration’, Sixth Edition while the current edition of FACT is Version 7. The TGA acknowledged that this creates complexities for sites that hold a TGA manufacturing licence in addition to being FACT accredited. 

TGA adopts ICH Guideline M10
TGA has adopted ICH guideline M10 on bioanalytical method validation and study sample analysis. This guideline provides guides on validation of bioanalytical assays to be used for clinical trial sample analysis. [6]

Australian Gene Technology Regulatory Scheme 
The Australian Department of Health and Aged Care is consulting on proposed amendments to the Gene Technology Act 2000 to update the Gene Technology Regulatory Scheme and make sure it remains fit for purpose [7]. The consultation closes on 8 November 2024. Proposed changes include (among other things) the addition of a permit pathway as an alternative to the licence pathway in certain cases, and rules in addition to regulations. [7] 

Australian Health Technology Assessment (HTA) Policy and Methods Review 
The HTA Policy and Methods Review Committee has concluded its review on 4 May 2024 and handed its final report to the Australian Government on 10 September 2024. The recommendations will have a profound effect on access to new and emerging treatments. For example, it recommends the establishment of a bridging fund for eligible therapies of high added therapeutic value that address high unmet therapeutic need, and improvements to the involvement of those impacted by HTAs in the assessment process. [8]   

INTERNATIONAL REGULATORY UPDATES RELEVANT TO AUSTRALIA & NEW ZEALAND
U.S. Food and Drug Administration (FDA) 
The FDA has approved AMTAGVI (lifileucel) by Iovance Biotherapeutics, a one-time T cell therapy treatment for people with previously treated melanoma that has spread or cannot be removed by surgery. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). [9]

The FDA has approved CARVYKTI by Janssen Biotech for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. [10]

WATCH THIS SPACE

TGA GMP forum – 19-20/NOV/2024 Melbourne, Australia
The Therapeutic Goods Administration’s GMP Forum 2024 is the ultimate platform for professionals looking to stay ahead of the curve in Good Manufacturing Practice. With a commitment to excellence, this event is designed to provide attendees with the latest information and best practices in GMP.  The Forum will cover the latest advances in the PIC/S Guide to GMP as well as snapshots of current industry-wide trends and issues from the regulators perspective [11].

REFERENCES

1. https://consult.health.govt.nz/medsafe/clinical-trials-guideline-updates/
2. https://www.tga.gov.au/news/media-releases/medtronic-australasia-pty-ltd-ordered-pay-22-million-largest-ever-penalty-unlawful-supply-therapeutic-goods
3. https://www.tga.gov.au/resources/publication/publications/tga-business-plan-2024-25
4. https://www.tga.gov.au/resources/publication/publications/medicine-shortages-report-2024
5. https://www.tga.gov.au/resources/consultation/consultation-clarifying-and-strengthening-regulation-artificial-intelligence-ai
6. https://www.tga.gov.au/resources/resource/international-scientific-guidelines/ich-guideline-m10-bioanalytical-method-validation-and-study-sample-analysis
7. https://consultations.health.gov.au/best-practice-regulation/amendments-to-the-gene-technology-act-200/
8. https://www.health.gov.au/our-work/hta-review
9. https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/amtagvi
10. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/carvykti
11. GMP Forum 2024 (eventsair.com)