When Radioisotopes go BOOM! Pharma Packaging Will Face a New Challenge

The global radiopharmaceutical market is expected to increase by $6.28 billion from 2024 to 2028, according to technology and research advisor Technavio. Cyclotrons, machines that use electromagnetic fields to produce radioisotopes for radiopharmaceuticals used to diagnose and treat disease, are helping to drive that growth.

New research and application areas for these novel isotopes will lead to huge upside growth in radiopharmaceuticals, according to Meixiang 'Max' Yu, PhD, scientific director of the Cyclotron Radiopharmaceutical Core at the Houston Methodist Research Institute.

The highly regulated clinical Positron Emission Tomography (PET) radiopharmaceutical manufacturing facility Yu directs has successfully delivered over 30,000 clinical doses for 16 different PET radiopharmaceuticals to clinical patients. These are for diagnostic purposes, especially in oncology, and include fluorine 18 (F18) FDG glucose metabolism imaging for cancer imaging, Gallium-68 (Ga68) PSMA for prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer, and Ga68 Netspot for somatostatin receptor-positive neuroendocrine tumor imaging, according to Yu.

“In our Translational Imaging Center, over 70% of the clinical trial studies are neurodegenerative diseases, including the F18 MK6240 for neurofibrillary tau and [carbon-11] C11 PIB a-beta amyloid in Alzheimer’s disease,” he said.

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These isotopes can be labeled to tracers for high-quality 3D PET imaging of organs and cells. And cyclotrons can produce some PET tracers in higher amounts and more rapidly than generators can, according to Yu.

Packaging requirements

Today’s most prevalent cyclotron-produced radioisotopes have short half-lives, losing their radioactivity within a few hours. The goals with packaging should be to assure not only safe, efficient, and accurate administration of the medicine but also to protect the nearby environment from unnecessary exposure and minimize contamination risk, Yu said.

“Our product is packaged in syringes with accurate decay corrected dose, and then distributed and transported using lead-shielded pigs, to provide protection from radiation exposure,” he said.

For safe handling, Yu points to “time, distance, shielding.”

Cyclotron-produced radiopharmaceuticals must be handled as quickly as safely possible, he said.

Packaging basics

Radiopharmaceuticals, including those produced using cyclotron-produced isotopes, are radioactive in nature. The energy associated with the radiation is different for different radioisotopes. Positron-emitting isotopes (PET drugs) produce 511 KeV gamma radiation through positron annihilation, which is considered high energy, according to the FDA.

“In general, for an injectable radioactive drug, the immediate container closure is similar to any other injectable drug product (e.g., a USP type I glass vial or a syringe). Particular attention is paid to assure container closure integrity to preserve sterility and to prevent leakage of radioactivity from the vial causing radioactive contamination,” an FDA spokesperson wrote in an email to Packaging Digest. 

The outer packaging consists of a radiation shielding material, such as lead, tungsten, etc., while the thickness of shielding depends on the isotope and radiopharmaceutical being packaged, according to the FDA.

The shielded vial may be packaged in a sealed tin can, which can be packaged in an outer carton for shipping. The Nuclear Regulatory Commission (NRC) and Department of Transportation (DOT) regulate the transport of radioactive materials, with DOT (49 CFR) covering all aspects of transportation, including packaging, shipper and carrier responsibilities, documentation, and all levels of radioactive material from exempt quantities to very high levels. NRC regulations (10 CFR 71) are primarily concerned with special packaging requirements for higher-level quantities.

Similar to typical radiopharmaceuticals

Packaging for cyclotron-produced radiopharmaceuticals is similar to that of typical radiopharmaceuticals. That’s because packaging for a radioactive drug is designed based on the type and the amount of radiation that it emits and not necessarily based on the method of production.

Radiopharmaceuticals designed for radiotherapy utilize an alpha-emitting isotope or a beta-emitting isotope.

“For an alpha-emitting product, the major concern is leakage and internal contamination of the exposed worker. Most of the alpha emitting radiation may be stopped by the vial, and secondary packaging, and heavy lead or tungsten shielding may not be needed. Other aspects will be similar to the gamma-emitting products,” the spokesperson wrote.

Health, safety, &environmental considerations

The concern with radiopharmaceuticals is external radiation exposure. Leakage poses the risk of internal exposure—including through ingestion.

These radiopharmaceuticals, however, do not tend to pose an environmental problem.

“The mass of materials associated with radioactive drugs is generally in the sub-microgram range and the radioactivity decays out over a short period of time. The resulting daughter product is also in correspondingly small sub-microgram amounts,” the spokesperson wrote.

Syringe and glass vial materials are generally disposed of along with other pharmaceutical products. The outer shielding material is generally recycled--in most cases is sent back to the radiopharmaceutical producer for reuse. The tin can be recycled or disposed of, and the outer container material is generally made of cardboard, which can be recycled, according to the spokesperson.

“Prior to recycling or disposal, all packaging materials are tested to assure that there is no residual radioactivity,” the spokesperson wrote.