Getting your Cell Therapy Product Approved in Australia Webinar Summary

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Zlatibor Velickovic, PhD, ANZ Regional Vice President
Facility Director, Cell & Tissue Therapies WA
Royal Perth Hospital, Perth WA

The International Society for Cell & Gene Therapy (ISCT) Regional Executive Committee for Australia and New Zealand (ANZ) organised an ISCT member-exclusive webinar titled "Getting Your Cell Therapy Product Approved in Australia—Some Dos and Don'ts." The webinar featured valuable insights from Australia's regulatory body, the Therapeutic Goods Administration (TGA), regarding the pathway for bringing cell therapy products to the market.

The webinar was hosted by A/Prof Zlatibor Velickovic, who is the ISCT ANZ Regional Vice President and Director of Cell and Tissue Therapies WA at the Royal Perth Hospital, along with Ms Jessica Sue, who serves as the ISCT ANZ Regional ESP Subcommittee Co-Chair and Quality Manager at the Sydney Cord Blood Bank. They extended a warm welcome to the speakers from the TGA, namely:

Dr Matt Adams, Senior Evaluator at the Biological Science Section at the Scientific Evaluation Branch,
Dr Tony Gill, Director of the Blood, Biologicals and Infectious Diseases Unit, and
Dr Glenn Smith, Director of the Biological Science Section at the Scientific Evaluation Branch.

Dr Adams provided an overview of the TGA. We learned that TGA is the federal government organisation responsible for overseeing the quality, safety, and efficacy of therapeutic goods in Australia, including medicines, medical devices, and biologicals such as cell therapies. The regulation of cell therapies depends on how the cells are modified. Products containing human cells or tissues derived ex vivo are classified as biologicals. On the other hand, those involving in vivo genetic modification, such as AAV vectors, are classified as medicines.

To market therapies in Australia, they must be registered on the Australian Register of Therapeutic Goods (ARTG). Several essential aspects must be addressed for a cell therapy seeking ARTG registration for commercial supply. These include obtaining Good Manufacturing Practice (GMP) licenses and certifications for all manufacturing sites involved and across the entire supply chain. Preparing a quality dossier is central the submission process. It should provide details on the control and testing of starting materials, such as demonstrating compliance with the required donor standards for allogeneic products. The dossier must also describe the final product's manufacturing process, analytical procedures, characterisation data, and labelling strategy. We learned that product characterisation is critical and includes defining the product's identity, purity, potency, and impurities. Extensive data from multiple clinical batches should justify the release testing criteria and provide a reference point for future variations.

From a non-clinical perspective, Dr Gill emphasised that pharmacology and toxicology studies are vital to establishing efficacy, determining safe starting doses, and identifying target organs and toxic effects. Justifying the choice of relevant animal models is essential. Conventional toxicity studies may only partially capture potential risks for some novel products, such as cell therapies. The limited clinical data for advanced therapies poses challenges in evaluating efficacy and safety.

There are concerns about accurately assessing off-target effects or secondary malignancies. As such, the TGA relies on risk management plans with post-marketing vigilance and follow-up commitments by sponsors. Establishing and maintaining patient registries is one good example. The presentation underscored the TGA's adoption of international guidelines and its evolving experience regulating this rapidly advancing field of cell-based therapeutics. An overarching theme was the importance of early interaction with the regulator and a strategic, scientifically justified approach tailored to individual products.

The webinar Q&A covered regulatory aspects related to cell therapy products from the audience's perspective. Clarity was provided on some cell therapy regulatory requirements, acknowledging that many specifics depend on the specific product and would require the TGA to evaluate each case individually.

Some key points made during the Q&A:

For allogeneic cell therapy products, the donor must meet the requirements of TGO 108 regarding donor selection, testing, and management. Other regulatory requirements, such as those around labelling (TGO 107) and product information (TGO 109), also apply. Validation of batch consistency across different donors is important for allogeneic products.
For clinical trials using a closed, automated manufacturing platform, it was unclear if reduced environmental control requirements (e.g. Class C/D instead of A/B) could be justified, as GMP principles still need to be followed for the manufacturing facility.
A GMP manufacturing license is not required for first-in-human clinical trials, but GMP principles must still be adhered to. However, a GMP-licensed facility is necessary for using the product beyond the first-in-human trial.
Regarding potency assays, each batch would need a validated potency assay as a release criterion, measuring the intended biological activity rather than just detecting the presence of the product. Single-cell RNA sequencing could potentially be used for purity/impurity characterisation if properly validated.
For overseas clinical trial applications, trials in Australia would still require notification/approval and ethics review at Australian sites. The TGA conducts GCP inspections examining GMP compliance for investigational products.
Viral vector manufacturing for delivering cell therapies follows medicines GMP regulations, while the introduction of cells makes it a biological product under the cell/tissue GMP code. mRNA manufacturing likely falls under the medicine regulations.

Overall, the webinar provided a comprehensive roadmap for sponsors navigating the complexities of bringing cell therapies through development and achieving marketing authorisation in Australia. Companies and organisations can facilitate an efficient and successful regulatory evaluation process by proactively addressing quality, non-clinical, clinical, and manufacturing requirements.

The webinar was well-attended live, and the recording is available on the ISCT website for ISCT members who have missed the live presentation.

We look forward to further updates from the TGA at the ISCT ANZ 2024 meeting, which will be held from 7 to 9 August in Queenstown, New Zealand. Everyone is welcome.