ANZ LRA Watchdog - June 2024

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Giulia Giunti, PhD¹
¹Regulatory Affairs Manager, BioOra Ltd, New Zealand

AUSTRALIAN AND NEW ZEALAND REGULATORY UPDATES

AOTEAROA – NEW ZEALAND
In May 2024, the New Zealand Government published the 2024 Budget, which outlines the government’s goal and allocates spending and reprioritization of resources, including Health, for the next three budgets [1].

Medsafe
Pharmacovigilance
Medsafe consulted on proposed updates to the Guideline on the Regulation of Therapeutic Products in New Zealand (GRTPNZ): Pharmacovigilance. The Guideline was last updated in 2020, with edition 2.2. The consultation was aimed at sponsors of medicines that are approved for use in New Zealand and organisations involved in pharmacovigilance activities (i.e., on behalf of sponsors) [2]. Following receipt and consideration of 15 submissions, a revised Guideline: GRTPNZ: Pharmacovigilance (Edition 3.0) was published. The revised Guideline comes into effect on 1 July 2024, but sponsors may use it from the date of publication (20 March 2024) [3].

Environmental Protection Authority (EPA)
The EPA has approved an application to release genetically modified cells as part of a clinical trial for a new cancer treatment. The WZTL-002 CAR-T cell product will be used in a phase 2 clinical trial for patients suffering from a type of blood cancer called relapsed large B-cell non-Hodgkin lymphoma [4].

AUSTRALIA
The Australian Government announced the Medical Research Future Fund (MRFF) 3rd 10-year Investment Plan in the 2024–25 Budget. The $6.5 billion investment plan updates and replaces the 2nd 10-year Investment Plan [5].

Therapeutic Goods Administration (TGA)
In February 2024, the TGA announced the launch of a pilot Single Inspection Program, a global approach to GMP inspections, in collaboration with Health Canada and the UK Medicines & Healthcare products Regulatory Agency (MHRA). This pilot aims to establish a coordinated global approach to GMP inspections of foreign manufacturing sites of common interest. The pilot is in the preliminary stages of identifying sites, so there will be no change to the overseas GMP inspection or clearance application processes [6].

In March 2024, the TGA updated the Uniform Recall Procedure for Therapeutic Goods (URPTG). The URPTG is for Australian sponsors who need to undertake actions (recall and non-recall actions) for therapeutic goods in Australia. It outlines the processes to respond efficiently and effectively to problems with therapeutic goods that could pose a risk to public health and safety. It also explains the roles and responsibilities of all stakeholders who are involved in therapeutic good recalls [7].

In May 2024, the TGA published an update to the ‘Guidance for clinical trial investigator sites on what to expect and how to prepare for an inspection’. Clinical trials of medicines, biologicals and medical devices regulated under the Clinical Trial Notification (CTN) or Clinical Trial Approval (CTA) are subject to the Good Clinical Practice (GCP) Inspection Program. TGA GCP inspectors assess whether Australian clinical trial sites are meeting their GCP responsibilities. GCP is an international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials. Compliance with GCP provides assurance that the rights, safety, and well-being of clinical trial participants are protected and that the trial data generated are credible [8].
The TGA is seeking feedback on

a. Proposed changes to the rules for Australian medicine labels for prescription and non-prescription medicines. Consultation closing date is 11/JUL/2024 [9].
b. The updated draft Companion Diagnostics (CDx) Guidance document. The proposed updates aim to provide sponsors and manufacturers of medicines, biologicals and IVD medical devices further clarification regarding the requirements for companion testing. An IVD companion diagnostic (CDx) is an in vitro diagnostic (IVD) medical device which provides information that is essential for the safe and effective use of a corresponding medicine or biological. Consultation closing date is 17/JUN/2024 [10].

INTERNATIONAL REGULATORY UPDATES RELEVANT TO AUSTRALIA & NEW ZEALAND
U.S. Food and Drug Administration (FDA)
In April 2024, the U.S. FDA released the draft guidance for industry Considerations for the Use of Human- and Animal-Derived Materials in the Manufacture of Cellular and Gene Therapy and Tissue-Engineered Medical Products [11]. The guidance discusses several key issues, including transmission of adventitious agents, and material lot-to-lot consistency, identity and qualification considerations, and how to present a material qualification justification within a regulatory submission. In addition, recommendations are provided regarding regulatory submissions related to the use of human- and animal-derived materials. This guidance supplements the 2020 guidance ‘Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)’ and the 2008 ‘Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)’.

In April 2024, the U.S. FDA released the draft guidance for industry Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products [12]. This guidance provides recommendations for determining the appropriate cell safety testing to support an Investigational New Drug Application (IND) or a Biologics License Application (BLA). This guidance supplements the 2020 guidance ‘Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)’ and the 2008 ‘Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)’.

The FDA has approved Beqvez, a Pfizer gene therapy developed for moderate-to-severe hemophilia B. The one-time treatment carries a $3.5 million price tag, the same as a CSL Behring gene therapy already available for treating the inherited bleeding disorder [13, 14].

MHRA
British Pharmacopoeia has published an ‘ATMP guidance for T Cell and NK Cell Characterisation Assays’ [15], which offers a practical set of guidelines to manage risk and develop robust processes.

EMA
In March 2024, The European Medicines Agency (EMA) issued a draft revision of the ‘Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials [16]. This guideline will provide updated guidance on the structure and data requirements for clinical trial applications involving exploratory and confirmatory trials with advanced therapy investigational medicinal products (ATMPs). These ATMPs include gene therapy medicinal products, cell therapy medicinal products, and tissue-engineered products. The guideline covers both non-clinical and clinical aspects of ATMP development in clinical trials. Consultation on the draft closed on 31/MAY/2024.

WATCH THIS SPACE
ISCT Regional Meeting ANZ – 7-9/AUG/2024 Queenstown, New Zealand
The ISCT Australia & New Zealand Regional Executive Committee is excited to welcome you to Queenstown, New Zealand and bring together our network of CGT professionals to address topics and current challenges to drive the field forward and break down barriers to enable greater access to patients [17].

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 [18].

REFERENCES

1. Budget prioritises frontline health services & workers | Beehive.govt.nz

2. Outcome of the consultation on the proposed updates to the Guideline on the Regulation of Therapeutic Products in New Zealand: Pharmacovigilance (medsafe.govt.nz)

3. GRTPNZ Part 8 Pharmacovigilance (medsafe.govt.nz)

4. Next step for cancer treatment trial | EPA

5. MRFF 3rd 10-year Investment Plan (2024–25 to 2033–34) | Australian Government Department of Health and Aged Care

6. Pilot GMP Single Inspection Program | Therapeutic Goods Administration (TGA)

7. Uniform recall procedure for therapeutic goods (URPTG) | Therapeutic Goods Administration (TGA)

8. Good Clinical Practice (GCP) Inspection Program | Therapeutic Goods Administration (TGA)

9. (Updates to Australian medicine labelling rules to support medicine safety - Therapeutic Goods Administration - Citizen Space (tga.gov.au)

10. Companion diagnostics guidance update- public consultation - Therapeutic Goods Administration - Citizen Space (tga.gov.au)

11. Considerations for the Use of Human-and Animal-Derived Materials in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products | FDA