Contrast Media Supply Shortage: How and What Now?

As the world, particularly the imaging community, is aware, disruptions in a pharmaceutical supply chain have impacted the global availability, and shortage of, iohexol iodinated contrast media (ICM), a common agent used in a multitude of CT and X-ray exams.

Getty Images

The theme “Everyday progress” seems appropriate for the imaging community in 2022. What a year it’s been. Supply disruptions which began when COVID-19 appeared on the world scene have severely impacted the way imaging is being managed, how exams are conducted, and how the industry looks to future modifications to work with the harsh realities that emerge from supply and demand issues looming large.

As the world, particularly the imaging community, is aware, disruptions in a pharmaceutical supply chain have impacted the global availability, and shortage of, iohexol iodinated contrast media (ICM), a common agent used in a multitude of CT and X-ray exams.

As is always the case in medicine, finding solutions is a top priority. Such has been the case under these unprecedented and consequential months. As we attempt to fully summarize here, with a nod to all engaged in this work, much has been accomplished. Here, we endeavor to offer a historical timeline, placing a spotlight on the research which has been conducted and reported on to provide long-lasting solutions.

Tackling this gargantuan imaging issue are a collection of what can best be termed “conservation strategists,” comprised of industry societies, radiology leaders at top institutions, along with their management and tech staffs, working collaboratively with government agencies and the four manufacturers whose product is in high demand daily.

Meanwhile, the work of developing strategies goes on, as does our coverage.

Supply Chain Status

It was in an April 19 letter to consumers that GE Healthcare announced it would limit order of its Omnipaque iohexol iodinated contrast media (ICM) for radiologic examinations. This was due to the shutdown of a plant in Shanghai which was closed under the Chinese government’s strict zero-COVID rules, which were imposed over a 2-month period. The factory reopened the first week of June. The company has reported it has also expanded production capacity at its manufacturing site in Cork, Ireland.

The latest publicly available update from GE Healthcare, issued July 15, stated:

“GE Healthcare’s Shanghai facility continues to operate at full capacity, and we expect some ongoing reduced availability of iodinated contrast media as we continue to restabilize global supply. We continue to keep our customers informed so they can plan accordingly.”

The company noted that its products, with a broad portfolio that stems across X-ray/CT, MRI and ultrasound modalities, are used in more than 100 million procedures globally every year, the equivalent to three patients being injected every second. It contends that the global demand for X-ray contrast media products has increased by more than 20% in the last three years, adding that it has strategically planned ways to help secure our supply of products.

On May 18, the company issued a letter to customers from Kevin O’Neill, President and CEO, Pharmaceutical Diagnostics GE Healthcare. In it, the company reported: “We are continuing to experience temporary supply issues for our iodinated contrast media products as a result of having to close our Shanghai fill and finish manufacturing facility for several weeks due to local COVID-19 policies. This is a fluid situation that we are working through daily, and our team is keeping impacted customers informed so they can plan accordingly.”

Supply and Demand

Estimates, as referenced in a June 9, 2022 JAMA article by Matthew Davenport, MD, et al show that approximately 54.4 million diagnostic imaging examinations using contrast are conducted annually in the US, including nearly all angiography and 48% of the 91.4 million computed tomography (CT) scans performed in 2019.

It remains the case that only four companies supply contrast media to the United States. Throughout the 2-month lockdown which resulted in supply disruptions, other manufacturers were unable to rapidly scale up ICM production to meet the demand created by the reduction.

Slow and steady progress is being made

We’ve been watching and reporting on developments, and continue to dig deeper into what’s next. Following the events, updates, studies and statements of all pertinent companies, medical societies and imaging industry leaders, ITN’s editorial team has coordinated a timeline of the most important events and updates provided from April through August, 2022.

Like the rest of our imaging community, Wainscot Media and its ITN and DAIC editorial team continues to vigilantly monitor this situation. As such, we welcome input from leaders and researchers devoted to working toward viable solutions, and always encourage communication with our team.

Recent Developments

• ARRS’ Journal of Roentgenology (AJR), on August 3, published EHR Interventions for Contrast Media Shortage Impact CT Utilization. The objective was to assess the impact of EHR order entry-based interventions, implemented as part of a health system’s response to the global contrast media shortage, on contrast-enhanced CT utilization. The open-access article (August, 2022) reported results exhibiting that electronic health record (EHR) order entry-based interventions implemented in response to the global iodinated contrast media shortage significantly reduced contrast-enhanced CT utilization within a large health system (primary author Daniel Glazer, MD, Brigham & Women’s Hospital, at Mass Gen – Harvard, Boston).

• Bracco Diagnostics Inc., a U.S. subsidiary of Bracco Imaging S.p.A., released an announcement on August 2, 2022, that the U.S. Food and Drug Administration (FDA) granted import discretion of Iomeron (iomeprol injection) into the U.S. to address the ongoing iodinated contrast media shortage, according to a news release issued July 27, 2022, from its Milian, Italy headquarters. Statement summary: “Iomeron (iomeprol injection) is currently registered in over 50 countries in Europe and Asia, it is not approved for use in the United States. The product will be temporarily available in the U.S. market starting at the end of August 2022. It is manufactured at two Bracco locations: BIPSO GmbH, Singen (Germany), and Patheon Italia S.p.A., Ferentino (Italy).”

• Research Letter published June 9 in JAMA: “Comparison of Strategies to Conserve Iodinated Intravascular Contrast Media for Computed Tomography During a Shortage” Matthew Davenport, MD, et al.

• RSNA Special Report, May 25, in Journal Radiology: Cardiothoracic Imaging, titled: “What the Baby Formula and Medical Contrast Material Shortages Have in Common: Insights and Recommendations for Managing the Iodinated Contrast Media Shortage” by Lakshmi Ananthakrishnan, et al.

Timeline

To offer perspective on the collaborative nature of the contrast media shortage problem-solving, this timeline covers significant events from April through August, 2022, with important updates and recommendations. Collectively, the current consensus appears to be focused on long-term conservation strategies.

APRIL:

China COVID-19 lockdown results in shutdown of GE Healthcare plant in Shanghai. The “zero-COVID” policy lasted two months, ending on May 30.

April 19: In a letter to consumers, GE Healthcare announces it would be limiting orders of iohexol. The facility has since reopened with production output currently at 50% and expected to increase. GE Healthcare also expanded production capacity at its manufacturing site in Cork, Ireland.

MAY

May 9: FDA adds GE Healthcare’s Omnipaque and Visipaque contrast media to its drug shortage list. An update from the American College of Radiology (ACR) to the medical community offered recommendations for providers in managing the shortage and supply disruptions. Since that statement, the ACR has continued to offer a range of resources to help practices continue to provide necessary care during this trying time.

May 13: ACR issues statement, including an updated ACR Contrast Manual.

The ACR Committee on Drugs and Contrast Media recommended considerations for facilities. An excerpt of the communication follows:

“The ACR Committee on Drugs and Contrast Media, within the ACR Commission on Quality and Safety, is aware of the current global shortage of iodinated contrast media. The statement offers recommendations on how providers may address this emergency locally. The recommendations are not exhaustive or prescriptive. They are intended as a resource for imaging providers and their institutions to continue to provide high-quality patient care during times of shortage of contrast media. Providers and administrative leaders are encouraged to incorporate sound clinical judgment in all decisions affecting patient care. The ACR recognizes that this is a rapidly evolving situation. Guidance may be revised as circumstances continue to change.”

May 13: The American Society of Health System Pharmacists (ASHP) issues Fact Sheet. It summarizes the status of the current acute shortage of iohexol, and provides an outline of potential actions for organizations to consider in managing the shortage.

The American Society of Nuclear Cardiology (ASNC) issues an Alert in response to GE Healthcare’s update. The statement recommends consideration of SPECT or PET as alternatives for CTA patients.

May 18: ARRS’ American Journal of Roentgenology (AJR) publishes “Best Practices for Iodinated Contrast Media Shortage.”

May 18: GE issues letter to customers from Kevin O’Neill, President and CEO, Pharmaceutical Diagnostics GE Healthcare.

May 19: Special Report published in RSNA Journal: Radiology, “Short-, Mid-, and Long-term Strategies to Manage the Shortage of Iohexol,” by lead author Thomas M. Grist, MD, FACR, Univ. of Wisonsin, et al. It provided consensus recommendations for dealing with the shortage of ICM in the near term, and discussed long-term issues and potential solutions to supply chain problems.

In a follow-up, Grist and Bruce G. Haffty, MD, 2022 President of RSNA, published, “Current shortage is a wake-up call to adapt the radiology supply chain.”

“It is too easy for us to take for granted the readily available supply of something that is so important to our patients and our radiologic practices until it’s gone,” noted Grist, adding, “We need to commit to changing the supply chain so that a single event in a faraway country does not put us in this predicament again. We owe it to our patients who trust us with their lives and well-being every day of the year.

“We are facing issues similar to those we faced in the early days of the COVID-19 pandemic, caused by a limited supply of an important pharmaceutical, critical to our ability to care for our patients,” Grist continued. “One important difference, however, is that our hospitals and health systems are more adept at establishing incident command centers to implement rapid responses to the challenges we face and communicating those changes to our patients and referring physicians.”

May 25: RSNA Special Report published in journal Radiology: Cardiothoracic Imaging, “What the Baby Formula and Medical Contrast Material Shortages Have in Common: Insights and Recommendations for Managing the Iodinated Contrast Media Shortage,” published by Lakshmi Ananthakrishnan, MD, et al. The authors described efforts at a large, academic safety-net county health system to conserve iodinated contrast media by optimizing contrast use in the CT department and changing ordering patterns of referring providers.

The recommendations stemmed from the authors’ work at Parkland Health, the safety net hospital serving Dallas County, Texas. The authors describe strategies implemented to optimize use of ICM in the radiology department, with a focus on CT services, and the methodology of the health system–wide response to limit use of contrast-enhanced CT (CECT) across a broad range of service lines.

JUNE

June 2: GE Healthcare issues a statement that it expected production capacity from its Shanghai facility to be close to 100% starting June 6, following the easing of local COVID-19 restrictions. It noted this would enable GE to restabilize its global supply of iodinated contrast media. GE stated that it will continue to work with impacted customers to help them plan several weeks ahead as supply progressively recovers. The facility has since reopened.

June 9: JAMA Research Letter publishes “Comparison of Strategies to Conserve Iodinated Intravascular Contrast Media for Computed Tomography During a Shortage,” by Matthew Davenport, MD, University of Michigan, et al.

As summarized in a University of Michigan Health Lab update, Davenport and a team of researchers modeled several ways to conserve contrast media. They found that a combination of methods could reduce contrast media use for CT scans by approximately 80% if a moderate reduction in diagnostic accuracy could be tolerated. The analysis of weight-based dosing and changing CT settings led researchers to examine what would happen if a system switched from fixed doses of contrast media to selecting the dose of contrast media based on the weight of each individual patient.

The team found that for a model of 1 million CT scans, moving to weight-based dosing could reduce contrast media use by 12%.

The second method they examined was changing the settings on the CT scanner, allowing the machine to better detect smaller amounts of contrast media. This adjustment, Davenport notes, works best for smaller patients.

“This strategy does not work well for larger patients due to increased image noise,” he said. “But in smaller patients, those who weigh under 80 kilograms, the contrast media dose can be reduced by up to 40%.”

June 14: GE Healthcare releases statement announcing Shanghai facility is operating at full capacity, which followed updates issued by the company on May 18, May 23, June 2, June 14 and July 15.

June: Bayer issues Letter to Health Providers noting, in part: “Bayer has engaged with the United States Food and Drug Administration to import and distribute a limited quantity of Ultravist (iopromide) stock which was originally intended and labeled for foreign markets. This imported stock is manufactured at the same site (Bayer AG, Berlin, Germany) that manufactures the Ultravist (iopromide) intended for the US market; however, it is not labeled with current FDA-approved labeling.”

JULY

July 14: FDA Notice of Important Prescribing Information published to include Bayer Healthcare Provider Letter sent to its customers July 14 regarding Ultravist, “Bayer Iodinated Contrast Shortage and Bayer’s Response.”

July 15: GE Healthcare statement, this the last published as of this writing August 25, 2022: “GE Healthcare’s Shanghai facility continues to operate at full capacity, and we expect some ongoing reduced availability of iodinated contrast media as we continue to restabilize global supply. We continue to keep our customers informed so they can plan accordingly.”

July 18: Fresenius Kabi on generic contrast media — Fresenius Kabi announced it will introduce a portfolio of generic contrast media agents in the United States, starting immediately with the launch of Iodixanol Injection, USP, a product the U.S. Food and Drug Administration (FDA) lists as being in shortage nationwide.

AUGUST

August 2: Bracco issues update, “FDA Grants Import Discretion of Bracco’s Iodinated Contrast Medium Iomeron (iomeprol injection) to Address Supply Shortages.”

August 3: ARRS’ Journal of Roentgeneology (AJR) publishes “EHR Interventions for Contrast Media Shortage Impact CT Utilization,” authored by Daniel I. Glazer, MD, Brigham & Women’s Hospital, Mass Gen, Harvard, et al. The paper detailed results of a study exhibiting how electronic health record (EHR) order entry-based interventions implemented in response to the global iodinated contrast media shortage significantly reduced contrast-enhanced CT utilization within a large health system.

The authors’ conclusion and clinical impact were reported as follows:

EHR order entry-based interventions implemented in response to the global contrast media shortage significantly reduced contrast-enhanced CT utilization within a large health system.

The findings indicate the ability to rapidly achieve changes in ordering clinician behavior and subsequent clinical practice using system-wide EHR changes.

Meeting the Challenge

With a global clarion call to those both on the front lines and behind the scenes of the contrast media shortage, the radiology community has proven its collective grit. Learning from peers whose conservation strategies provide long-term solutions, while laser focused on delivering high quality imaging to patients, continue to be top priorities. As research and new conservation methods continue, a sense of community and collaboration in dealing with the contrast media supply chain issue has showcased the value and the vision of the industry at its best.