Radiopharmaceuticals sit at an unusual crossroads. They are medicines, but they are also radioactive materials with short half-lives, tightly constrained logistics, and specialist clinical governance. Over the past eighteen months, regulators in Europe, the UK and the United States have signalled a clear intention to modernise oversight in ways that better reflect the development, manufacturing, distribution and administration of radiopharmaceuticals. The most consequential developments cluster around three themes: manufacturing standards and lifecycle control, clinical development expectations, and system-level resilience of radioisotope supply.
This article summarises the latest regulatory and governance movements and what they may mean for developers, manufacturers, hospitals and sponsors planning clinical trials.
Europe: A Push to Update the Core GMP Framework for Radiopharmaceuticals
One of the most significant recent moves in Europe is the decision to revisit the specialised Good Manufacturing Practice (GMP) annexe that addresses radiopharmaceuticals. In December 2025, the European Medicines Agency (EMA) and PIC/S opened a public consultation on a concept paper to revise GMP Annex 3, “Manufacture of Radiopharmaceuticals”. This is the backbone reference that guides EU-aligned inspectors and manufacturers in their approach to radiopharmaceutical production and quality systems.
The importance of this consultation lies not only in its existence but in what it signals. Annex 3 has long needed clearer alignment with modern practice, particularly where radiopharmaceutical manufacturing intersects with radiation protection requirements, the realities of rapid batch release, and the complexity of multi-site supply chains. The concept paper identifies updates that should help unify expectations across routine manufacturing, importation, distribution arrangements, and recall preparedness, while also clarifying quality control and certification considerations specific to time-sensitive products.
The proposed timetable also matters for planning. The consultation window closes in mid-February 2026, but the broader work programme is staged over several years, with drafting and further consultation anticipated later. For organisations investing in new capacity or reconfiguring supply networks, the direction of travel is clear even if the final text is some way off: EU regulators want an annexe that better reflects contemporary radiopharmaceutical science and operational constraints.
Europe: Sharper Focus on Clinical Evaluation for Therapeutic Radiopharmaceuticals
Alongside GMP modernisation, the EMA has been developing the foundations for clearer clinical evaluation expectations for therapeutic radiopharmaceuticals, especially in oncology. A concept paper published in October 2024 set out the rationale for future guidance on how evidence should be generated and assessed for therapeutic radiopharmaceuticals, while also clarifying how pharmaceutical and radiation-protection legislation interact during development.
This matters because therapeutic radiopharmaceuticals often sit between conventional drug development and radiation dose considerations, which can create uncertainty in trial design, dose selection rationale, and endpoint strategy. Regulators are increasingly attentive to demonstrating a robust benefit–risk profile that properly accounts for radiobiology, dosimetry approaches, and the practicalities of repeat dosing or combination regimens. While the concept paper is not a full guideline, it is an early indicator of a more structured regulatory posture. Sponsors developing novel targeted radioligand therapies should anticipate more consistent questioning on dose justification, radiation risk management, and the evidence needed to support claims across therapeutic areas.
Europe: Lifecycle Change Control Becomes More Structured
Radiopharmaceutical manufacturing is operationally dynamic. Sites change, raw materials fluctuate, analytical methods evolve, and distribution chains may need to be redesigned quickly to protect patient access. In that context, the EU’s revised approach to post-approval change management is highly relevant.
From 1 January 2025, the revised EU “variations” framework has been in force, supported by updated European Commission guidelines published in 2025. Although this reform is not radiopharmaceutical-specific, it influences how efficiently marketing authorisation holders can make changes without jeopardising compliance or continuity of supply. The practical implications are most acute where products have single points of failure: a key starting material, a radionuclide supply route, a critical piece of production equipment, or a specialist testing method.
For companies with mature portfolios, this development is as much governance as it is regulation. It strengthens the case for systematic comparability planning, proactive engagement with authorities when major changes are foreseeable, and internal decision-making structures that prioritise supply continuity alongside regulatory compliance. For newer entrants, it reinforces the need to build lifecycle strategies early rather than treating variations as a post-launch administrative burden.
The UK: Updated Clinical Governance Through ARSAC Guidance
In the UK, radiopharmaceutical governance is shaped not only by medicines regulation but by the approval and licensing environment for the clinical administration of radioactive substances. The Administration of Radioactive Substances Advisory Committee (ARSAC) remains central to this system, and its Notes for Guidance were updated in 2025.
While the details are technical, the wider importance is straightforward: ARSAC guidance influences how organisations demonstrate competence, oversight and safe practice in the administration of radiopharmaceuticals and use of sealed sources. It affects how responsibilities are defined across clinicians, medical physics teams, radiopharmacy staff and organisational leadership. For healthcare providers, changes in guidance can trigger updates to local procedures, training documentation, audit readiness and governance reporting. For industry partners supplying products into NHS environments, it shapes the operational reality of how a product is delivered, handled and administered, including what supporting information services may need to provide to sites.
The UK: A New Regulatory Framework for Point-of-Care and Modular Manufacture
A more structural UK development is the emergence of a dedicated framework for decentralised and point-of-care manufacture, which is directly relevant to radiopharmaceuticals and other short-lived medicines. The UK regulator has published a series of materials describing modular manufacture and point-of-care models, including governance concepts such as “hub and spoke” arrangements and the role of a “control site”.
For radiopharmaceuticals, the potential impact is substantial. Many products are prepared in hospital radiopharmacies or in close proximity to clinical settings because transport time degrades usable activity. Clearer regulatory pathways for decentralised models can reduce ambiguity around who holds what responsibilities, how quality oversight is maintained across multiple sites, and how batch release, deviation management and pharmacovigilance responsibilities are allocated.
In governance terms, this is about making systems safer while acknowledging real-world constraints. A well-designed decentralised model can improve access and resilience, but only if responsibility, oversight, and documentation are unambiguous. Organisations considering expansion into hospital-based production, satellite preparation sites, or multi-site clinical trial supply should treat this framework as a prompt to revisit quality agreements, oversight structures and inspectorate expectations.
The UK: Clinical Trials Regulation Reform With a Firm Start Date
The UK has also confirmed a major regulatory shift for clinical trials, with new regulations scheduled to take effect on 28 April 2026 after an implementation period. Radiopharmaceutical clinical trials, particularly those involving therapeutic agents, can be among the more complex CTIMPs to run because they combine conventional clinical trial governance with radiation-related safety considerations and specialist site readiness requirements.
The practical meaning for sponsors is that trial planning in 2026 will need to account for a changing approvals environment, evolving safety reporting expectations and updated procedural requirements. The safest approach is to assume that trial documentation, internal SOPs, vendor oversight arrangements, and site support packages will need to be refreshed, especially if a programme spans the transition period.
The United States: FDA Emphasis on Dosage Optimisation for Oncology Therapeutic Radiopharmaceuticals
In the United States, the FDA published a draft guidance in August 2025 focused on dosage optimisation during clinical development for oncology therapeutic radiopharmaceuticals. This is a clear signal that regulators want stronger evidence and clearer logic around the selection of administered activities, schedule optimisation, and how dose choices will translate into meaningful clinical benefit.
For sponsors, this affects more than the dose-escalation phase. It influences how early-phase endpoints are chosen, how dosimetry or exposure-response analysis may be incorporated, and how the overall development programme is justified from a benefit–risk standpoint. It also has downstream implications for labelling discussions, post-marketing commitments, and real-world use patterns. The governance message is that “standard dosing by convention” is less likely to satisfy regulators when optimised dosing can be justified through well-designed development.
Supply Resilience as Governance: Radioisotopes Move Higher on the Policy Agenda
A final thread running through these developments is the security of supply. Medical radioisotope availability has increasingly been treated as a strategic resilience issue rather than merely a procurement challenge. European institutions have taken steps to strengthen supply security and build capacity, and broader international analysis has continued to document fragility in the supply ecosystem and the impact of outages.
For radiopharmaceutical stakeholders, this translates into a more explicit expectation of resilience planning. Manufacturers may be asked about contingency supply routes, redundancy for critical inputs and the robustness of distribution networks. Healthcare systems may strengthen governance around prioritisation during shortages, communication pathways and alternative diagnostic or therapeutic pathways. Sponsors designing trials may need to build mitigations for isotope disruption into risk management plans and feasibility assessments.
What This Means in Practice
Taken together, these developments point to a more mature regulatory environment that is catching up with how radiopharmaceuticals are actually made and used. Europe is moving towards updated GMP expectations and clearer clinical development frameworks, while also tightening the structure around post-approval change control. The UK is strengthening clinical governance and creating more explicit pathways for decentralised production, alongside imminent reforms to clinical trials. The US is sharpening expectations around dose optimisation in oncology therapeutic radiopharmaceutical development.
The direction is consistent: regulators want clarity of responsibility, stronger evidence packages, and systems that protect patients while supporting access. For industry and healthcare providers, the near-term priority is governance readiness: quality systems that can accommodate change, clinical programmes that anticipate evolving expectations, and supply models that do not rely on optimistic assumptions.
Disclaimer
This article is provided for general informational purposes only and reflects publicly available regulatory and policy developments at the time of writing. It does not constitute legal, regulatory, clinical, or professional advice and should not be relied upon as a substitute for consultation with competent regulatory authorities or qualified professional advisers. Regulatory requirements and interpretations may evolve, vary by jurisdiction, and depend on specific product, organisational, or clinical circumstances. Readers are responsible for ensuring compliance with applicable laws, regulations, and guidance relevant to their activities.
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