Radiopharmaceutical Support for Disease Applications

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Radiopharmaceuticals, including targeted diagnostics and therapeutics (theranostics), hold significant promise for specific diseases, particularly certain cancers and neurological conditions. Recognizing the unique convergence of challenges in this field, Regal Intel provides specialized, non-profit guidance to innovators developing these complex therapies for rare disease patient populations. Our support covers tailored regulatory strategies integrating orphan pathways (IND, NDA/MAA), critical radiation safety considerations for vulnerable patients and personnel, addressing complex CMC hurdles (radionuclide handling, short half-lives, GMP compliance), designing appropriate clinical trials incorporating dosimetry for rare populations, establishing specific pharmacovigilance systems, ensuring comprehensive radiation safety training, and managing intricate logistics for potentially dispersed patients. Our mission is to help navigate these combined complexities to accelerate access to potentially life-changing radiopharmaceutical treatments for rare diseases.

Navigating the regulatory landscape requires mastering both pharmaceutical/biologic regulations and distinct radiation safety requirements (e.g., FDA & NRC in the US; EMA & national competent authorities under Euratom Treaty in the EU). We provide comprehensive regulatory strategy development tailored for disease radiopharmaceuticals, integrating requirements for Orphan Drug Designation, expedited pathways, and pediatric plans where applicable. Our services include:

• Strategic planning and preparation for regulatory interactions (e.g., Pre-IND, Pre-NDA/MAA meetings).
• Expert compilation and submission of dossiers (IND, NDA/MAA, etc.) in eCTD format, addressing both drug/biologic and radiopharmaceutical-specific data (CMC, preclinical, clinical, dosimetry).
• Ensuring radiation dosimetry calculations and safety assessments meet stringent regulatory and ethical standards for rare disease populations.
• Compliance review for specific labeling and packaging guidelines for radiopharmaceuticals.

The manufacturing of radiopharmaceuticals for rare diseases involves unique challenges, often compounded by smaller batch sizes or the need for specialized manufacturing partners. Regal Intel provides expert consulting on:

• Establishing and maintaining GMP compliance specifically for radiopharmaceutical production.
• Guidance on compliant radionuclide sourcing, safe handling, and waste management.
• Developing and validating robust analytical methods for quality control, addressing challenges like short half-lives.
• Designing appropriate stability studies and determining shelf-life for these unique products.
• Consulting on facility design, environmental controls, and implementation of effective radiation protection measures.

Clinical trials require specialized expertise to ensure patient safety and gather meaningful data, particularly, for example, in rare disease populations. Regal Intel assists with:

• Designing clinical trial protocols that incorporate appropriate radiation safety measures, patient-specific dosimetry calculations (including pediatric considerations), and endpoints.
• Strategies for patient monitoring, emphasizing safety in potentially vulnerable populations throughout the trial.
• Managing adverse event reporting tailored to the unique safety profile of radiopharmaceuticals.
• Handling and statistically analyzing specialized imaging and dosimetry data from radiopharmaceutical trials, addressing challenges of small sample sizes.

Ongoing safety monitoring is critical, given the novel nature of many radiopharmaceuticals and their use, for example, in specific rare disease populations, often following expedited approvals. Regal Intel provides:

• Development of tailored pharmacovigilance systems capturing unique adverse events and long-term safety data.
• Efficient global adverse event reporting and signal detection suitable for potentially sparse datasets.
• Development and implementation of Risk Management Plans (RMPs) or REMS specific to radiopharmaceutical risks.
• Support for designing and executing post-market clinical follow-up studies often required for these therapies.

Ensuring radiation safety for personnel, patients, and caregivers is paramount. Regal Intel offers:

• Customized radiation safety training programs for personnel involved in manufacturing, handling, administration, and clinical research.
• Development and implementation of comprehensive Radiation Protection Programs compliant with regulatory requirements.
• Guidance on ALARA (As Low As Reasonably Achievable) principles implementation to optimize protection.
• Conducting facility audits and compliance assessments to verify adherence to radiation safety standards.

The delivery of radiopharmaceuticals, especially those with short half-lives, requires meticulous planning, particularly when reaching potentially geographically dispersed rare disease patients or specialized treatment centers. Regal Intel provides guidance on:

• Optimizing "just-in-time" supply chain management for time-sensitive products.
• Ensuring safe and compliant transportation, handling, and storage of radioactive materials.
• Managing cold chain requirements where applicable to maintain product integrity.