In Australia, radiopharmaceutical manufacturing facilities must comply with ARPANSA (Australian Radiation Protection and Nuclear Safety Agency) safety regulations and TGA (Therapeutic Goods Administration) Good Manufacturing Practice (GMP) requirements.

• ARPANSA regulations ensure that facilities incorporate radiation shielding, exposure control, and environmental safety to protect workers and the public. Facilities must follow ALARA principles (As Low As Reasonably Achievable) for radiation exposure.

• TGA GMP standards, aligned with PIC/S (Pharmaceutical Inspection Co-operation Scheme) guidelines, mandate that radiopharmaceuticals are produced in controlled environments, including ISO 14644 cleanroom classifications.

• National standards like AS/NZS 2982 (Laboratory Design) and ANSTO guidelines provide additional benchmarks for compliance.

To operate, facilities must meet both radiation safety codes (ARPANSA, state radiation regulators) and pharmaceutical GMP (TGA, PIC/S, ISO 14644) to ensure the highest levels of safety, sterility, and product quality.

Radiopharmaceutical production follows strict international regulations:

• FDA (United States): 21 CFR Part 212 applies to PET drug manufacturing, enforcing sterility and quality controls under cGMP (Current Good Manufacturing Practices).

• EMA (Europe): EudraLex Volume 4, Annex 3 mandates that radiopharmaceuticals meet EU GMP standards, with strict control over sterility and radioactive contamination.

• IAEA (International Atomic Energy Agency): Publishes global safety and GMP guidelines for radiopharmaceutical facilities, used as a reference in emerging regulatory frameworks.

Most global facilities align with FDA, EMA, PIC/S GMP, and IAEA recommendations to ensure compliance across multiple regulatory jurisdictions.

Radiopharmaceutical facilities require specialized layouts to ensure radiation safety, sterility, and workflow efficiency. Key best practices include:

✔ Zoned Facility Layout: Separate hot (radioactive) and cold (non-radioactive) areas to prevent cross-contamination. Maintain a unidirectional material and personnel flow.
✔ Radiation Containment & Shielding: Use hot labs, lead-lined walls, and tungsten shielding to protect workers.
✔ HEPA Ventilation & Negative Pressure: Install filtered HVAC systems with directional airflow, ensuring radioactive containment and cleanroom sterility.
✔ Automation & Remote Handling: Reduce radiation exposure using robotic arms, automated synthesis units, and remote-controlled dose dispensers.
✔ Decontaminable Surfaces: Construct with seamless, chemical-resistant materials for easy sterilization and radiation safety.
✔ Integrated Radiation Monitoring: Install real-time radiation detectors and hand-foot contamination monitors at entry/exit points.

A well-designed facility minimizes radiation risks, ensures GMP compliance, and maximizes efficiency in drug production.

Radiopharmaceutical production involves sterile injectables, requiring highly controlled cleanroom environments.

• Grade A / ISO Class 5: Used for final product dispensing and aseptic filtration, typically inside a hot cell isolator.

• Grade B / ISO Class 7: Background area for Grade A environments, ensuring controlled air cleanliness and sterility.

• Grade C / ISO Class 8: Used for preparation and formulation areas before final aseptic processing.

• Grade D / ISO Class 9: General production zones requiring controlled environmental monitoring.

Environmental controls include HEPA filtration, cascading airlocks, positive pressure for sterility, and negative pressure inside hot cells to contain radiation.

Radiation shielding is essential to protect staff and ensure regulatory compliance. Facilities use:

✔ Lead or Tungsten-Lined Hot Cells: Shielded workstations with glove ports for handling radioactive materials.
✔ High-Density Concrete Vaults: Used for cyclotron rooms to contain neutron and gamma radiation.
✔ Radiation Maze Entrances & Shielded Walls: Designed to minimize radiation leakage into public areas.
✔ Lead-Glass Viewing Windows & Interlocks: Prevent accidental exposure while allowing observation of high-radiation processes.

Radiation safety designs are validated by health physicists before facility approval.

Key equipment includes:

• Cyclotron – Particle accelerator for producing radioisotopes, housed in a shielded vault.

• Hot Cells – Lead-lined enclosures where radiopharmaceuticals are synthesized and dispensed.

• Automated Synthesis Modules – Robotic systems for precise radiopharmaceutical formulation.

• Dose Calibrators – Used to measure radioactivity in patient doses before shipment.

• Radiation Monitoring Systems – Real-time detection of contamination or leakage.

This specialized infrastructure ensures safety, sterility, and compliance in radiopharmaceutical production.

Facilities must complete two key approval processes:

1. ARPANSA / State Radiation Licensing: Submit radiation safety plans, shielding designs, and risk assessmentsfor regulatory approval. Pre-operation, a radiation survey ensures compliance.

2. TGA GMP Licensing: Implement quality management systems (QMS), cleanroom validation, and process qualification to meet PIC/S GMP standards. Facilities undergo TGA audits before approval.

Both licenses require regular compliance audits to maintain operational status.

International compliance involves:

✔ FDA (U.S.) GMP Certification: Requires 21 CFR Part 212 compliance, aseptic process validation, and radiation safety protocols.
✔ EMA (EU) GMP Authorization: Follows EudraLex Vol. 4, Annex 3 for radiopharmaceuticals, with stringent sterility and product validation.
✔ IAEA Safety Standards: Global reference for best practices in radioactive material handling and facility design.

Most multinational facilities follow FDA, EMA, and IAEA standards to ensure global market acceptance.

Yes, modular facilities offer faster deployment, flexibility, and compliance advantages:

• Pre-Fabricated Cleanrooms & Shielded Hot Labs – Delivered as turnkey GMP-compliant units.

• Scalability & Cost Efficiency – Allows quick capacity expansion without full facility reconstruction.

• Portability & Mobile Solutions – Enables temporary or remote radiopharmacy setups.

Modular radiopharmaceutical facilities are gaining traction due to their reduced construction time and regulatory adaptability.

Automation and AI-driven solutions enhance efficiency, safety, and regulatory compliance:

✔ Robotic Dose Dispensing – Reduces manual handling and radiation exposure.
✔ SCADA & Process Control Systems – Real-time monitoring of HVAC, hot cells, and radiation safety.
✔ Digital Batch Records (LIMS) – Automates compliance tracking and documentation.
✔ AI & Predictive Analytics – Detects equipment failures before they impact production.

These Pharma 4.0 advancements improve productivity, traceability, and regulatory compliance.