Scaling Clinical Operations for One of Australia's First NAM-Enabled First-in-Human Trials

1. Introduction

Preclinical drug development is changing. New Approach Methodologies (NAMs) are increasingly replacing traditional animal testing as the foundation for predicting human safety and efficacy. These methodologies include in-vitro human-based systems, in-silico computational modelling, and microphysiological platforms such as organ-on-chip technologies.¹

This transformation received significant legislative support in December 2022, when President Biden signed the FDA Modernization Act 2.0 into law. This landmark legislation explicitly authorised the use of non-animal alternatives, including cell-based assays and computer models, to support Investigational New Drug (IND) applications, effectively removing the blanket mandate for animal testing that had been in place since 1938.^2,3

In April 2025, the FDA released a comprehensive roadmap outlining its strategic approach to reducing animal testing in preclinical safety studies. The roadmap identifies monoclonal antibodies as the initial focus, with plans to expand to other biologics and eventually new chemical entities. The document envisions a future where "no conventional animal testing will be required for mAb safety, and eventually all drugs/therapeutics."⁴

1.1 Global Regulatory Alignment

The FDA's initiative has catalysed similar movements internationally. Australia and Europe have demonstrated considerable openness to NAMs adoption, in some cases advancing faster than US counterparts.⁵ Human Research Ethics Committees (HRECs) play a critical role in this transition, as they are responsible for evaluating the scientific validity and ethical acceptability of trial protocols incorporating novel methodologies.

In Australia, Bellberry Limited, one of the nation's leading private HRECs, has emerged as a champion for responsible NAMs adoption. On 30 November 2024, Bellberry and the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) hosted an introductory workshop in Melbourne examining how Australia can support the responsible use of NAMs to reduce reliance on animal models, improve translational outcomes, and facilitate the transition into first-in-human trials.⁶

This work has continued to gain momentum. At AusBiotech 2025 in Melbourne (October 2025), Bellberry presented further case studies demonstrating the practical application of NAMs in Australian clinical trials, including the trial described in this case study.⁷

1.2 Australia's Value Proposition

Australia offers compelling advantages for international biotechnology companies seeking to conduct early-phase clinical trials:

Streamlined Regulatory Framework: Australia's Clinical Trial Notification (CTN) scheme provides a rapid pathway to trial initiation without requiring an IND submission. Under the CTN scheme, the Therapeutic Goods Administration (TGA) is notified of a clinical trial after HREC approval, rather than evaluating preclinical data packages as required by the FDA. This typically enables trial commencement within 6–8 weeks of submission.^8,9

Internationally Accepted Data: Clinical research data generated in Australia is accepted by the FDA and European Medicines Agency (EMA), enabling seamless continuation of development programs across jurisdictions. Australian trials adhere to ICH-GCP guidelines and are subject to TGA inspection, ensuring data quality meets international standards.¹⁰

R&D Tax Incentive: The Australian Government's Research and Development Tax Incentive program provides eligible companies with a refundable tax offset of up to 43.5% on qualifying R&D expenditure, including clinical trial costs. For companies with aggregated turnover below AUD $20 million, this represents a direct cash refund. This is a significant advantage for early-stage biotechnology companies operating at a loss.^11,12

World-Class Infrastructure: Australia maintains internationally recognised research facilities, experienced investigators, and access to diverse patient populations, supported by a robust healthcare system and stable intellectual property protections.¹⁰

2. Case Study

This case study describes clinical operations undertaken independently of this consultancy. The author was employed directly by the sponsor, a US-based biotechnology company operating a vertically integrated business model. The author led the establishment of Australian clinical operations from inception through trial execution.

The program involved one of Australia's first First-in-Human clinical trials for a half-life extended monoclonal antibody targeting an autoimmune indication. The preclinical development package incorporated NAMs including in-silico pharmacokinetic and immunogenicity modelling, advanced in-vitro assays, and organ-on-chip technologies.

2.1 Operational Scope

The author's responsibilities encompassed the full spectrum of clinical trial operations, including:

Regulatory Strategy: Coordination of TGA submissions, HREC applications, and site-specific governance approvals. Navigation of drug importation requirements and establishment of compliant supply chains for investigational product.

Site Activation: Establishment of an owned clinical trial site, including procurement and calibration of medical and laboratory equipment, development of standard operating procedures, and training of clinical staff.

Vendor Network Development: Identification and qualification of local vendors for pathology services, safety assays, clinical assays (pharmacokinetics, pharmacodynamics, anti-drug antibodies, biomarkers), and participant recruitment.

Trial Execution: Coordination with healthcare professionals for trial conduct, participant screening and enrolment, sample collection and processing, safety monitoring, and data management through to study close-out.

Business Operations: Project management, budget development and tracking, contract negotiation with service providers, and ongoing stakeholder communication with US-based leadership.

2.2 Key Outcomes

The program achieved site activation within six months of project initiation. This covered regulatory approvals, site establishment, vendor qualification, and readiness for first participant dosing. This timeline demonstrates the efficiency achievable through Australia's streamlined regulatory environment when combined with experienced operational leadership.

3. Discussion

The successful execution of this NAM-enabled FIH trial required solutions to challenges spanning regulatory strategy, vendor network development, and site operational readiness. The learnings from this experience inform the consultancy services offered by Scalable Trials.

Australia's regulatory framework, combined with the R&D Tax Incentive and internationally recognised data quality, positions the country as an attractive destination for international sponsors seeking to advance early-phase clinical programs. The growing adoption of NAMs by HRECs such as Bellberry further enhances this value proposition, enabling sponsors to leverage human-relevant preclinical data packages in their regulatory submissions.

For biotechnology companies considering Australian clinical trials, experienced operational leadership can significantly compress timelines and reduce risk. The complexity of establishing local infrastructure, from regulatory navigation to vendor qualification to site activation, benefits from personnel with direct, hands-on experience in the Australian clinical trials ecosystem.