Unintended consequences of the potential phase-out of gamma irradiation

Rationale for phase-out of Co-60

The widespread commercial use of Co-60 means it is often housed in less well-guarded facilities, such as hospitals, that are unlike heavily guarded nuclear facilities⁹. Experience in other countries has demonstrated the potential for mishaps. For example, in 2013, thieves in Mexico stole a truck transporting Co-60. The thieves ultimately abandoned the Co-60, as the material itself did not appear to be the target, and the authorities recovered it¹⁰. Also in 2013, online fashion retailer Asos recalled a batch of metal-studded belts contaminated with Co-60 likely introduced in scrap metal from India or another Asian country¹¹. In both of these cases, it was incidental exposure to Co-60 that posed the greatest public health risk, rather than the potential for a terrorist act. To date, these types of Co-60 mishaps have not been reported in the United States, perhaps because of this country’s stricter regulations. There have been no deaths from exposure to radiation or any history of contaminated groundwater at irradiators in the US. The US Nuclear Regulatory Commission (NRC) has reviewed cases of radiation incidents and has developed strict requirements designed to reduce future risk of incidents (10 CFR (Code of Federal Regulations) Part 36, implemented in 1993.) (https://www.nrc.gov/reading-rm/doc-collections/fact-sheets/commercial-irradiators.html)

Ongoing regulatory changes and additional safety and security requirements have been implemented over the years to further increase and assure maintenance of safe and secure handling, transport and use of high activity radioactive sealed sources. The US NRC promulgated 10 CFR Part 37 in March 2013 with adoption required by US NRC licensees by March 2014 and Agreement State licensees by March 2016. (https://www.nrc.gov/reading-rm/doc-collections/cfr/part037/) Part 37, “Physical Protection of Category 1 and Category 2 Quantities of Radioactive Material”, provides specific detail of control in the following areas:

Desirable properties of Co-60

Co-60 has three main advantages. First, the gamma radiation it produces is versatile. Gamma radiation can deeply penetrate a wide range of low- and high-density materials^1,12,13. Deep penetration is important for sterilizing medical supplies and to reach pathogens deep within the food matrix¹⁴. Because gamma radiation does not require high temperature, it can be used on temperature-sensitive items, products can be irradiated in bulk, and sterilization can take place after final packaging^15,16.

Second, Co-60 is reliable. It has a simple and predictable decay pattern and a relatively long half-life (5.27 years). Treatment with Co-60 is precise and reproducible;^15,17–19 (http://www.world-nuclear.org/information-library/non-power-nuclear-applications/radioisotopes-research/radioisotopes-in-medicine.aspx, http://www.world-nuclear.org/information-library/non-power-nuclear-applications/overview/the-many-uses-of-nuclear-technology.aspx) therefore, instrument calibration standards rely on Co-60 as a “gold standard” yardstick²⁰. Co-60 gamma irradiators are simple to use and control^1,3,12, and because the Co-60 itself generates the radiation, it is energy-efficient¹⁵. These properties minimize operational maintenance requirements¹⁵.

Finally, Co-60 has favorable physical characteristics that make it ill-suited to manipulation that could pose security risks. It cannot start a fission chain reaction, it is non-flammable, and it cannot poison a water supply because it is insoluble. Moreover, because Co-60 is not readily dispersible, it does not emit neutrons or leave residues, or cause other surrounding materials to become radioactive^15,16.

Limitations of Co-60 alternatives

Alternative sterilization technologies include chemical treatment, non-ionizing radiation, and other ionizing radiation sources (Table 1). Chemical treatments pose a series of challenges.^1,21. Ethylene oxide (EO) requires complex equipment, is toxic, and flammable, and poses an explosive hazard. EO can be inconsistent because its use depends on multiple variables—including temperature, time, pressure, vacuum, and concentration—to address differences in the target material’s physical characteristics (e.g., density and porosity), packaging, and humidity^3,12. Peracetic acid-ethanol, although rapid²² and compatible with a wide variety of materials, significantly reduces biomechanical strength, decreases remodeling activity in ligament grafts¹ and does not reduce infection risk²². Heat treatment damages many materials. For example, steam autoclaving damages plastics which comprise many single-use items. Although evidence is limited and it can only treat heat-resistant materials²², microwave treatment has been shown to effectively sterilize some bone allografts¹.

Alternative ionizing radiation sources have both advantages and drawbacks. Like gamma radiation, e-beam can sterilize health care products on a commercial scale¹ and is currently used in many large facilities. E-beam delivers radiation rapidly and can be scaled³. However, because the radiation is machine-generated, rather than a material by-product (as is the case with Co-60-generated gamma radiation), the equipment is complex and costly to install and operate. Nor is e-beam radiation as predictable or uniform as Co-60 gamma radiation¹. Finally, e-beam radiation does not penetrate materials as well as gamma radiation. X-ray radiation achieves penetration comparable to that achieved by gamma rays³. However, similar to equipment used to generate e-beam, x-ray generating equipment is complex, expensive and less reliable than Co-60, with very few such sterilization units operating globally^3,13,17,23. (http://www.world-nuclear.org/information-library/non-power-nuclear-applications/overview/the-many-uses-of-nuclear-technology.aspx, http://www.iaea.org/inis/collection/NCLCollectionStore/_Public/29/057/29057259.pdf)

Sterilization of single-use medical supplies

Current estimates indicate that the sterilization industry is divided between EO (50%), gamma (40.5%), e-beam (4.5%) and other (including x-ray) (5%), and there are 200 healthcare facilities worldwide with commercial gamma sterilization capability²³. Co-60 is the most widely used form of radiation for sterilizing single-use medical products¹⁶, as heat sterilization is often damaging, and alternative methods might not achieve sufficient penetration^17,23. (http://www.world-nuclear.org/information-library/non-power-nuclear-applications/overview/the-many-uses-of-nuclear-technology.aspx) Single-use medical products were used in over 52 million surgical procedures in the US in 2011, with 45% of single-use products sterilized using Co-60^23,24.

Curtailing radioisotope sterilization would make availability of some single-use products uncertain, hence potentially jeopardizing millions of surgical procedures yearly. At the very least, products for which the effectiveness of alternative sterilization technologies has not been established would have to undergo significant and both time and cost intensive testing^25,26. In the case of products for which adequate sterilization proved infeasible, single-use medical products could become unavailable going forward. Predicting the impact of this disruption on health is difficult. We do not know how many technologies would be affected, for how long, or the adequacy of substitute or redesigned products. However, with the possibility that millions of surgeries could be affected, it is clear that curtailing use of radioisotope materials for single-use medical supply sterilization could be highly disruptive.

Tissue allograft sterilization

More than 2 million allografts each year support more than 1 million annual tissue transplants². Used in reconstructive surgery for musculoskeletal injuries, allografts avoid the major complications associated with use of autogenic materials¹. In addition, allograft skin and amniotic membrane have unique properties that make them irreplaceable and indispensable in the treatment of serious burn injuries¹. The risk of transmitting infectious disease from donor to recipient necessitates sterilization.

Sterilization alternatives for tissue allografts (ethylene oxide, peracetic acid-ethanol, thermo-disinfection), microwave, electron beam) lack the same demonstrated effectiveness as gamma radiation^1,21. Studies have identified insufficient penetration as a key limitation of alternative sterilization technologies¹. Although some evidence indicates that microwave sterilization is effective for bone allografts²⁸, evidence supporting microwave sterilization in general, and its use for other tissues is limited compared to the evidence for gamma radiation.

Even if more extensive evidence were available, a phase-out of radioisotope sterilization could trigger FDA regulatory testing requirements²¹ and delay replacement of existing sterilization technologies, potentially affecting the supply of tissue allografts.

Gamma knife surgery

Gamma Knife is a stereotactic radiosurgery technique that relies on Co-60⁶. Approximately 70,000 Gamma Knife surgeries take place worldwide each year, with nearly 1 million surgeries having been conducted from 1991–2013. (https://gammaknife.com/downloads/Facts%20in%20short_1028438.01.pdf) While alternatives exist, the Gamma Knife technique, described in Table 2, is the most established, well-researched and validated form of radiosurgery. (http://nyulangone.org/locations/center-for-advanced-radiosurgery/gamma-knife-radiosurgery)

Gamma Knife is specifically indicated for brain surgeries. Radiosurgery using Co-60 is non-invasive and accurate to 0.15mm. Because it can target small areas, Gamma Knife can be used more extensively than competing technologies that deliver larger tissue doses of radiation because they cannot be as finely focused^29,30. The more precise targeting achieved by Gamma Knife also causes less damage to healthy tissue, speeding recovery and minimizing side effects³¹. In a prospective cohort study in which physicians assigned and treated patients with either gamma knife radiosurgery or whole brain radiotherapy (follow-up of 1200 days, or 3.3 years), the mortality rate was lower for Gamma Knife patients (74.4% vs. 97.1%), and the median survival time greater (9.5 months for Gamma Knife versus 8.3 months for whole brain radiotherapy patients)³². With approximately 70,000 gamma knife surgeries each year⁶ and 1.2 added months (9.5-8.3) gained per surgery, eliminating Gamma Knife could potentially cost 7,000 life-years annually. Curtailing Co-60, which the Gamma Knife depends on, would eliminate the only demonstrated treatment for certain tumor types.

Slowed innovation

A ban on radioisotope sterilization technologies could also slow medical innovation. Modifications to sterilization modalities could involve costly redesign and require additional validation for the sterilization process, the sterilization product itself, and its packaging²³. First, altering the sterilization method constitutes a major change to new drug applications (NDA) and abbreviated new drug applications (ANDA), requiring FDA approval prior to distribution of drug products²⁶. The added effort could divert resources away from development of new technologies. Alternative sterilization methods may require new 510(k) or premarket applications (PMA). For 510(k) applications, the FDA determines whether the device is at least as safe and effective as a legally marketed device (“substantial equivalence”)^5,8. Although the process is supposed to take no more than 90 days, one sterilization company noted that the full FDA clearance process lasts 9 months. (http://www.revoxsterilization.com/sites/default/files/Revox_OsteoArticle.pdf) The FDA believes that novel sterilization technologies “carry a substantial risk of inadequate sterility assurance if not conducted properly”. (https://www.fda.gov/downloads/MedicalDevices/.../ucm109897.pdf) Therefore, recent guidance indicates that in the context of a novel sterilization process, FDA intends to inspect manufacturing facilities before clearing a 510(k). (https://www.fda.gov/downloads/MedicalDevices/.../ucm109897.pdf) PMA applications or supplements require up to 180 days of review time, depending on the product’s regulatory classification, design, and other required changes⁵.

Second, because these reviews will divert FDA’s resources, FDA’s approval of other new technologies will likely slow. The FDA already has a backlog of products awaiting approval. Further slowing the overburdened approval system could delay patient access to life-saving therapies³³. (https://www.cato.org/publications/commentary/fda-can-be-dangerous-health)

Third, a Co-60 phase-out will raise manufacturing costs. It costs on average $31 million to bring a low-to-moderate 510(k) product from concept to market, with approximately three-quarters of the cost related to FDA-dependent or related activities. Costs for PMAs are $94 million, with $75 million related to the FDA process³⁴. By raising costs, a Co-60 phase-out could disincentivize future innovation.

Finally, Co-60 sterilization facilities are often located near medical device manufacturers or distribution hubs. Phasing out of these facilities would reduce the attendant supply chain efficiencies, potentially increasing consumer prices, delaying product availability, and reducing supply.

Food products

The US food supply relies heavily on gamma radiation. Co-60 is used for food preservation, shelf-life extension, and reduction of food-borne illness for domestic and international food products, including microbial disinfection of spices. (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm279485.htm) Most spices sold in the US are grown overseas in developing countries, where pollution and water issues can contaminate food shipped to this country. (http://www.washingtonpost.com/wp-dyn/content/article/2010/03/13/AR2010031301111.html) Irradiation is also used as a quarantine treatment for fresh horticultural commodities, and as a substitute for fumigants in Asian countries and the US⁷. (https://uw-food-irradiation.engr.wisc.edu/Process.html)

Phasing-out Co-60 will likely affect US and global food supply chains as alternatives are established. Alternatives to Co-60 have characteristics that limit their ability to treat all food products requiring irradiation. Because gamma irradiation can completely penetrate a product, it can deactivate both surface pathogens and those found within the food matrix (see Table 3)¹⁴. With almost a quarter of the world’s food irradiation units located in the US³⁵, switching to alternatives to Co-60 irradiation may cause some disruption to the global food supply system. There is potential for impacts to food prices, supply, and access, depending on how quickly the global food irradiation system would be able to respond to a US phase-out.

Decommissioning costs

Like food products, consumer goods prices will likely increase in response to a Co-60 phase-out, as decommissioning current Co-60 facilities will be costly. In February 1999, a decommissioning project commenced for a gamma irradiation facility at the Brookhaven National Laboratory (BNL), located on Long Island, New York³⁶. The decommissioning process was involved, taking over a year to conduct three main phases: 1) preparation of the facility; 2) packaging and shipment of irradiation sources for disposal; 3) disposal/discharge of pool water (used for cooling) and dismantling. Ultimately, all 24,000 curies of cobalt-60 were removed.

Building replacement facilities is also resource-intensive, with food irradiation facilities estimated to cost between $3-5 million, (https://uw-food-irradiation.engr.wisc.edu/Process.html) and the equipment alone required for an electron accelerator for medical device sterilization estimated to cost between $1 and $2 million³⁷. There is little publicly available information on the full spectrum of cost for Co-60 facilities, including facilities large enough for medical sterilization, but conservatively, they likely cost several million dollars. Consumer products, medical products, and food products that involve Co-60 for sterilization would all be affected by the cost of decommissioning and construction of new facilities for replacement sterilization.