The U.S. Food and Drug Administration’s role in improving radiation dose management for medical X-ray imaging devices

Abstract

The U.S. Food and Drug Administration (FDA) has been concerned with minimizing the unnecessary radiation exposure of people for half a century. Manufacturers of medical X-ray imaging devices are important partners in this effort. Medical X-ray imaging devices are regulated by FDA under both its electronic product regulations andits medical device regulations. FDA also publishes guidance documents that represent FDA’s current thinking on a topic and provide a suggested or recommended approach to meet the requirements of a regulation or statute. FDA encourages manufacturers to develop medical devices that conform to voluntary consensus standards. Use of these standards is a central element of FDA’s system to ensure that all medical devices marketed in the U.S. meet safety and effectiveness requirements. FDA staff participate actively in the development and maintenance of these standards, often advancing or introducing new safety and dose management requirements. Use of voluntary consensus standards reduces the amount of time necessary to evaluate a premarket submission and reduces the burden on manufacturers. FDA interacts with industry and other stakeholders through meetings with industry groups, public meetings, public communications, and through the development of voluntary consensus standards. In these interactions, FDA staff introduce new concepts for improving the safety of these devices and provide support for similar initiatives from professional organizations. FDA works with all stakeholders to achieve its mission of protecting and promoting the public health.

Introduction

The U.S. Food and Drug Administration’s (FDA) mission is to protect and promote the public health.¹ FDA has been concerned with minimizing unnecessary radiation exposure of people for more than 50 years, since the passage of the Radiation Control for Health and Safety Act of 1968.^2,3 More recently, FDA’s concerns regarding unnecessary radiation exposure from medical imaging were expressed in a 2010 white paper⁴ and FDA’s activities related to the Bonn Call for Action were described.^5,6 This review describes how FDA regulates medical X-ray imaging devices and works with equipment manufacturers and others to improve radiation dose management and radiation protection in medicine. Manufacturers of medical X-ray imaging devices are important partners in this effort.

FDA OVERSIGHT OF MEDICAL X-RAY IMAGING DEVICES

FDA’s authority over medical imaging devices is derived from specific statutes and their implementing regulations. These regulations are contained in Title 21 of the Code of Federal Regulations (21 CFR), subchapters H (Medical Devices), I (Mammography Quality Standards Act), and J (Radiological Health). Compliance with FDA regulations is mandatory for manufacturers of regulated medical devices and electronic products who wish to sell them in the U.S. FDA also publishes guidance documents that represent FDA’s current thinking on a topic but are not binding on FDA or the public. They are a suggested or recommended approach to meet the requirements of a regulation or statute. An alternative approach to the one suggested or recommended in the guidance document is acceptable if it satisfies the requirements of the applicable statutes and regulations. FDA has published several guidance documents related to medical X-ray imaging devices,^7–12 some of which are discussed in this review. Note that mentions of laws, FDA regulations and guidance documents in this review do not describe the full extent of requirements and recommendations applicable to electronic products and medical devices. Please see the relevant laws, regulations and guidance documents for full details.

FDA encourages but does not require manufacturers to develop medical devices that conform to voluntary consensus standards. A voluntary consensus standard is one developed by an organization that plans, develops, establishes, or coordinates standards using a voluntary consensus standards development process that meets U.S. government requirements.¹³ Use of voluntary consensus standards by manufacturers is a central element of FDA’s system to ensure that all devices marketed in the U.S. meet safety and effectiveness requirements. Their use reduces the amount of time necessary for FDA to evaluate a premarket submission and reduces the burden on manufacturers, who often are required to conform to these standards in order to market their devices in other countries. Of particular importance for medical imaging devices are the standards of the International Electrotechnical Commission (IEC). The IEC is a standards development organization that develops international standards for electrical and electronic devices and systems, including medical X-ray imaging devices.^14,15

FDA maintains a Standards and Conformity Assessment Program (S-CAP) under which FDA can identify (“recognize”) standards as appropriate for manufacturers to declare conformance to in order to meet relevant FDA requirements, including premarket submission requirements.¹³ Under S-CAP, FDA seeks to drive the development, recognition, and appropriate use of voluntary consensus standards for medical devices, radiation-emitting products and emerging technologies.¹⁶ Recognition of international voluntary consensus standards promotes global harmonization of premarket device evaluation.

Regulation of medical X-ray imaging devices as electronic products

The Radiation Control for Health and Safety Act of 1968, subsequently incorporated into sections 531 through 542 of the Food, Drug and Cosmetic Act (FD&C Act), gave FDA the authority to set federal radiation standards, to monitor compliance, and to conduct research.¹⁷ Radiation exposure from medical X-ray imaging devices was one of the initial areas addressed under the law. An early advance was the development by FDA engineers of automatic collimators for positive beam limitation in radiographic systems, to limit field size to the area of the film.³

At present, much of FDA’s efforts under this portion of the FD&C Act are related to regulation of electronic products. In brief, electronic products contain or are part of an electronic circuit and emit (or without adequate shielding or other controls would emit) electronic product radiation. Electronic product radiation includes any ionizing or non-ionizing electromagnetic or particulate radiation and any sonic, infrasonic, or ultrasonic wave emitted from an electronic product as the result of the operation of an electronic circuit in that product (21 CFR 1000.3(k)). Medical X-ray imaging devices are therefore regulated as electronic products. Certain electronic products are required to meet specific performance standards. Among these are diagnostic X-ray systems and their major components, including radiographic, fluoroscopic, and CT systems.¹⁸ These performance standards are in addition to the regulatory requirements that must be met by medical devices.

Regulation of medical X-ray imaging devices as medical devices

FDA also regulates medical X-ray imaging devices and their manufacturers under its medical device regulations and the 1976 Medical Device Amendments and subsequent amendments to the FD&C Act.^19,20 With the exception of mammography,²¹ FDA does not regulate users of these devices—users are regulated by the individual states. Medical devices are classified as Class I, Class II, or Class III based on the device’s intended use and indications for use and the degree of risk the device poses to patients and users.²² The lowest risk devices are Class I; the highest risk devices are Class III. Class I devices (e.g. bandages, hospital beds) use well understood or simple technology, and their safety and effectiveness are well established. Class II devices are more complex and present moderate risk. Most medical X-ray imaging devices are regulated as Class II devices. Some Class I, most Class II, and all Class III medical devices are subject to premarket review. There are three different premarket review processes for medical devices. Before marketing a Class II device in the U.S., the manufacturer must demonstrate to FDA, through a premarket submission (the 510(k) process), that the device to be marketed is as safe and effective as an existing, legally marketed device (“substantially equivalent”).²³ The De Novo review process applies to low or moderate risk products that are not substantially equivalent to any identifiable predicate device²⁴; for the De Novo premarket process manufacturers must demonstrate that they understand all the probable risks and benefits, explain the measures needed to effectively mitigate the risks, and demonstrate that device safety and effectiveness can be assured through the application of general controls or general and special controls.²⁵

Class III devices are complex and present the highest risk (e.g. life sustaining or life supporting) or represent new technology. They are reviewed through the Premarket Approval (PMA) process. Unlike the 510(k) process, which is comparative, PMA review requires that manufacturers independently demonstrate safety and effectiveness.²⁶ Class III devices may be down classified to Class II when sufficient information becomes available to establish regulations (Special Controls) that reasonably assure safety and effectiveness.^25,27

Finally, under the Mammography Quality Standards Act (MQSA), FDA regulates the practice of mammography.²¹ FDA has regulations (21 CFR 900) regarding mammography personnel, quality control, record keeping, and medical audit, including image quality requirements and a maximum average glandular dose per exposure (21 CFR 900.12(e)(5)).^11,28

Interactions with industry

International Electrotechnical Commission

Certain IEC standards are particularly relevant to medical X-ray imaging devices. FDA radiological health staff participate actively in developing and maintaining these standards as members and convenors of IEC committees. Meetings of these committees give FDA staff the opportunity to interact with industry members, other regulatory agencies, and clinical stakeholders on an informal, non-regulatory basis. FDA staff participate in the development of IEC standards for the safety and essential performance of radiography, fluoroscopy, interventional fluoroscopy, CT, dental imaging, and mammography systems, among others. In these committees, FDA often advances or introduces new safety and radiation dose management requirements that then become part of IEC standards. Some of these are described below.

Medical Imaging & Technology Alliance

In the U.S., the principal group that represents manufacturers of medical X-ray imaging devices is the Medical Imaging & Technology Alliance (MITA), a division of the National Electrical Manufacturers Association (NEMA). NEMA is also a U.S. standards development organization. FDA radiological health staff typically meet with one or more individual MITA modality sections and groups (e.g. X-ray section, interventional X-ray group, CT section, computed radiography/digital radiography group) at least twice a year to discuss matters of mutual interest. At these meetings, FDA staff often introduce new concepts for improving safety of these devices and provide support for similar initiatives from professional organizations such as the American Association of Physicists in Medicine (AAPM) and the American College of Radiology (ACR). For example, FDA worked with MITA to improve education of CT technologists by manufacturers and supported ACR’s Dose Index Registry by encouraging manufacturers to provide radiation dose structured report (RDSR) capability in radiography systems. As another example, after extensive discussion with MITA, FDA published a guidance document that clarified the meanings of fluoroscopic irradiation time and last-image-hold in FDA’s performance standards (21 CFR 1020.30 and 12 CFR 1020.32).⁸ These clarifications were subsequently incorporated into the IEC standards for safety and essential performance for radiography and fluoroscopy²⁹ and for interventional fluoroscopy.³⁰

FDA has worked with, and encouraged, MITA to develop certain X-ray standards related to CT and interventional fluoroscopy.^31–33 Since development of NEMA standards, which are U.S. national standards, is often more rapid than revision of international standards, FDA often works with MITA to develop a NEMA standard first, and then advances the NEMA standard for inclusion into an updated international standard.

Use of IEC standards in lieu of FDA’s performance standards

FDA has determined that for certain medical X-ray imaging devices, conformance to certain IEC standards would provide, at a minimum, the same level of protection of the public health and safety from electronic radiation as certain electronic product performance standards.⁷ These devices include certain radiographic, fluoroscopic, mammographic, dental, and CT equipment. In 2019, FDA published a guidance document that announced that, for these devices, conformance to certain IEC standards would be deemed to meet certain FDA performance standards requirements.⁷ As part of the development of this guidance document, FDA worked with industry to ensure that end users would not need access to IEC standards in order to be able to test these medical X-ray imaging devices adequately.

An additional way that consensus standards can be used is in FDA-required compliance testing for certain performance characteristics. This testing is specified in the performance standards for diagnostic X-ray equipment, but FDA has identified methods in recognized IEC voluntary consensus standards that may be used for assessment of image quality and radiation dose in lieu of methods specified in the performance standards.³⁴

Specific imaging modalities and issues

Radiography and fluoroscopy

The first performance standards were introduced in 1972. They addressed diagnostic X-ray systems and their major components, including tube housing assemblies, X-ray controls, high-voltage generators, and beam-limiting devices in radiographic and fluoroscopic systems.³⁵ Among other requirements were the provision to users of adequate instructions for any radiological safety procedures and precautions necessary because of unique features of the equipment, a schedule of the maintenance necessary to keep the equipment in compliance with the performance standards, and requirements for X-ray field limitation, visual beam-on indicators, and the accuracy, reproducibility and linearity of technique factors. For fluoroscopic equipment, the 1972 performance standards included entrance exposure rate limits and requirements for a primary protective barrier, minimum source-to-skin distance, and a fluoroscopic timer. The most recent substantive revision of the performance standard for diagnostic X-ray systems, in 2005,¹⁸ increased the required minimum half-value layer values for new radiographic and fluoroscopic equipment. For fluoroscopic equipment, it also required last-image-hold capability, display of cumulative air kerma and air kerma rate to the operator, and amended the X-ray field limitation and alignment requirements to promote the addition of features designed to reduce the amount of radiation falling outside the visible area of the image receptor, thereby preventing unnecessary patient exposure. Most of these requirements were subsequently incorporated into the relevant IEC standards.

FDA draws attention to important safety issues through public communications, such as public health advisories and information for physicians and other health professionals. An example of a safety issue, and the effect of FDA public communications, is radiation-induced skin injuries from interventional fluoroscopy. In the early 1990s, reports of these injuries began to appear in the medical literature.³⁶ In October 1992, ACR and FDA sponsored a workshop on fluoroscopy safety and related issues.³⁷ One of the outcomes of that workshop was a focus on equipment issues, including the inability to monitor patient radiation dose and a lack of dose metrics other than fluoroscopy time. Because of these reports, FDA published a 1994 Public Health Advisory warning physicians and hospitals of the occurrence of these injuries,³⁸ a 1995 recommendation to record patient radiation doses on the medical record,³⁹ and a 1996 paper on these injuries.⁴⁰ These led to widespread recognition of the problem in the U.S., and were at least partially responsible for the subsequent development of international guidance on how to avoid these injuries,⁴¹ the first IEC standard on safety and essential performance for interventional fluoroscopy systems,⁴² and the first attempts at providing a real-time skin dose map during interventional fluoroscopy procedures.⁴³

More recently, FDA worked closely with Image Gently and AAPM members to develop new items for inclusion in amendments to the current IEC standards for safety and essential performance for radiography and fluoroscopy²⁹ and for interventional fluoroscopy.³⁰ Image Gently had worked with MITA to develop questions for consideration in the design of fluoroscopy equipment.⁴⁴ FDA approached Image Gently with a request for recommendations for inclusion in IEC standards, with the goal of improving dose management and enhancing safety in pediatric radiography and fluoroscopy. Image Gently provided specific recommendations. At the same time, FDA consulted AAPM members with extensive experience with these modalities for additional recommendations to enhance safety, improve dose management for both adults and children, and aid medical physics experts in quality assurance and system evaluation. FDA evaluated the suitability of these recommendations for inclusion in IEC standards and introduced them during the IEC discussions of revisions for these standards.

The final published standards for both radiographic and fluoroscopic systems incorporated these FDA-introduced items. These were: provision to the purchaser of instructions and acceptance criteria for manufacturer-recommended quality control procedures and tests to be performed by the facility; provision for facility access to and export of electronic documentation of examination protocols; a requirement for systems with automatic intensity control to have a quality control mode; a recommendation that the system create an RDSR DICOM object, populate the relevant elements of the RDSR, and be able to export it; for systems without automatic exposure capability, at least three patient size choices selectable by the operator for adult patients, and if the intended use includes pediatric patients, at least three patient sizes selectable for pediatric patients; for fluoroscopy equipment, a recommendation to be able to store 10 sec or 300 images of fluoroscopic imaging, whichever is less, and a requirement to display fluoroscopic pulse rate and pulse width for systems where these are adjustable.

FDA-introduced items specific to interventional fluoroscopy systems included: establishment and definition of an emergency fluoroscopy mode of operation; a maximum time of 10 min to recover from a recoverable system failure, with a recommendation of less than 1 min to recover those functions necessary to operate in emergency fluoroscopy mode; a minimum pulse rate no greater than four pulses/sec if the fluoroscopy pulse rate is selectable; a requirement for the unit of display for kerma–area product to be configurable by the facility; and a requirement for the location of the collimator edges to be displayed graphically on the last-image-hold image when the collimator is adjusted but fluoroscopy is not active. In cooperation with AAPM members, FDA developed and actively supported a recommendation that a dose map should be displayed, that a skin dose map is preferred, and that a dose map cannot be called a skin dose map unless the dose quantity measured and displayed is skin dose.

CT

In the early 1980s, it became apparent that a dose descriptor was needed to permit evaluation of the radiation dose impact of different scanning techniques and different CT scanners. In 1981, FDA physicists developed a method, the CT dose index (CTDI), for describing the absorbed dose delivered by CT scanners.⁴⁵ CTDI became the predominant method for measuring radiation dose from a CT system; a revised version is still in use today.⁴⁶ CTDI was subsequently incorporated into FDA’s performance standard for CT (21 CFR 1020.33(c)(2)) and the IEC standard for the safety and essential performance of CT.^47,48

The 1972 performance standards for radiography and fluoroscopy were not accompanied by a performance standard for CT, as the first CT scanner in the U.S. was not installed until 1973.⁴⁹ FDA’s performance standard for CT equipment was introduced in 1985. This standard listed the required technical and safety information that manufacturers must provide to end users. This included specification of values for CTDI and the radiation dose profile, as measured with the CT dosimetry phantom; a separate section of the user manual with quality assurance instructions, display prior to initiation of the scan of CT conditions of operation to be used during a scan, and the capability to terminate the X-ray exposure automatically in the event of equipment failure affecting data collection. Manufacturers were also required to provide the end user with instructions on terminating the X-ray exposure at any time during a CT scan.

The NEMA CT Dose Check standard was an outgrowth of the lessons learned during FDA’s investigation of the anomalously high radiation exposures during certain CT brain perfusion studies that were first reported in 2009. In a November 2010 letter to MITA,⁴⁷ FDA proposed several ideas to decrease the possibility of unintended high exposure; one of these was a “pop-up notification at threshold for deterministic injury.”⁵⁰ MITA responded rapidly and issued the CT Dose Check standard in 2010.⁵¹ The pop-up notification suggested by the FDA became the Dose Alert in this NEMA standard. All of the major manufacturers of CT scanners now include Dose Check on their new CT scanners and provide software upgrades for many of their older CT scanners. The previous and current IEC standards for safety and essential performance of CT scanners require that CT scanners support Dose Check.

Manufacturers continue to develop CT features to reduce radiation dose. FDA works with them and other stakeholders in this effort. One example is the collaborative effort between FDA and MITA to evaluate CT iterative reconstruction.⁵² Another is AAPM’s Alliance for Quality Computed Tomography.⁵³ FDA is a member of this AAPM workgroup that has published multiple CT protocols,⁵³ CT Dose Education presentations, and an updated CT lexicon. It has also provided contributions to the NEMA standard on CT user information³³ and recommendations on how to use the NEMA CT Dose Check standard.⁵¹

Dental imaging

Dental handheld and cone-beam CT (CBCT) equipment have become increasingly popular, have been the subject of concerns and inquiries from dentists and state regulators, and have resulted in FDA safety notices and other public communications for patients and dentists.^54,55 FDA analyzed the existing IEC standards for dental X-ray imaging devices and identified important aspects of the safety and performance of dental CBCT and handheld X-ray equipment that are not addressed by current IEC standards or FDA’s electronic product performance standards. To address this gap, FDA collaborated with stakeholders, including dental device manufacturers, AAPM, the Conference of Radiation Control Program Directors (CRCPD), and dental radiologists, to revise the IEC standards for the basic safety and essential performance of dental intra oral equipment⁵⁶ and panoramic, cephalometric and CBCT equipment.⁵⁷ FDA has also been involved in developing a new IEC standard for acceptance and constancy testing of dental CBCT equipment (61223-3-7, based in part on FDA’s work with the National Council on Radiation Protection and Measurements (NCRP) on Report No. 177, the update to NCRP Report No. 145.⁵⁸

The next editions of the IEC standards for intra oral and extra oral dental X-ray equipment will include provisions to provide the purchaser with a device-specific phantom or software for manufacturer-recommended quality control procedures. The revised IEC standard for extraoral equipment will include provisions for CBCT systems to create RDSRs. This will simplify collection of patient dose data to help ensure that all patients, and especially pediatric patients, are imaged safely. The next edition of the IEC standard for dental intra oral equipment will include provisions to prevent unauthorized initiation of radiation from handheld dental X-ray equipment and will require manufacturers to provide accessories for positioning the image receptor and restriction of the irradiated area. FDA also made several recommendations specific to dental handheld equipment that will be part of the next edition, including radiation leakage limits, tests to check leakage radiation and means to protect the operator from stray radiation.

Pediatric imaging

FDA seeks public and professional input for policy and guidance development through public meetings and workshops. Two such public meetings, Device Improvements to Reduce Unnecessary Radiation Exposure from Medical Imaging (March 30–31, 2010)^59,60 and Device Improvements for Pediatric X-ray Imaging (July 16, 2012),⁶¹ were held to solicit feedback from all stakeholders on how FDA could best address radiation safety issues in X-ray imaging modalities. Some specific recommendations received, such as making pediatric protocols and pediatric control settings and dose information available, and providing targeted instructions and educational materials emphasizing pediatric dose reduction, were eventually incorporated into the November 28, 2017 guidance document, Pediatric Information for X-ray Imaging Device Premarket Notifications.⁹ This document offers a framework for how manufacturers can consider radiation safety for patients of all sizes and ages, including pediatric patients, as part of the device risk assessment that encompasses the design, testing, and labeling of their device. As a result of the efforts of FDA and other stakeholders, the latest IEC CT standard includes Size Specific Dose Estimates (SSDE) to ensure that dose is better represented for patients of all sizes.⁶²

The NEXT program

FDA collaborates with CRCPD, an organization comprised of state radiological health regulators and professionals, to perform periodic surveys of U.S. clinical facilities that perform a selected diagnostic X-ray procedure. This partnership is called the Nationwide Evaluation of X-ray Trends (NEXT) Program.⁶³ Since its initiation in 1972, the NEXT program has surveyed a broad spectrum of diagnostic X-ray procedures. Each survey gathers a broad array of data regarding the clinical practice of X-ray imaging at approximately 250–350 randomly identified facilities.

FDA has collaborated with device manufacturers and clinicians to train state radiological health regulators to gather survey data at participating clinical sites. For example, for the 2008 cardiac catheterization survey, Siemens provided classroom instruction during the NEXT training courses. For the 2018–2019 survey of chiropractic sites, the American Chiropractic Association and American Chiropractic College of Radiology provided a letter of support encouraging invited sites to participate in the survey. The program has received clinical support from AAPM, NCRP, and radiologists who have served as resource individuals and provided advice during training, survey data collection and assimilation.

The NEXT program captures the state of diagnostic clinical X-ray practice. These survey data provide a solid foundation that supports regulatory and outreach-based efforts by FDA and other organizations. As an example, a primary tool for reducing the exposure of the general public to ionizing radiation is the use of Diagnostic Reference Level (DRL) values for various X-ray modalities.⁶⁴ NEXT data have been used extensively in the U.S. to support the derivation of such values.^58,65,66 NEXT data were also used in the development of an International Code of Practice published by the IAEA International Atomic Energy Agency in 2007.⁶⁷ These reports address important clinical aspects of medical X-ray imaging. In addition, NEXT survey findings are used by many state radiological health programs to further support their own public health efforts to reduce patient exposure during diagnostic X-ray procedures. Many state programs have used past NEXT survey findings to recommend state-level values for X-ray exposure limits similar to DRLs.⁶⁸

Other FDA activities in radiation protection

FDA staff serve as members of scientific committees, task groups, and working parties of the NCRP, the International Commission on Radiological Protection, the International Atomic Energy Agency, the World Health Organization, and the U.S. Interagency Steering Committee on Radiation Standards (www.iscors.org), among others, and have contributed to multiple publications related to radiation protection in medicine. FDA has also provided funding for activities such as Image Gently’s fluoroscopy modules, which provide information on how to image pediatric patients more safely, and NCRP Report No. 177 on radiation protection in dentistry.^58,69

Conclusion

FDA regulates medical X-ray imaging systems both as medical devices and as electronic products. In addition to these regulatory efforts, FDA works with manufacturers and other stakeholders to protect and promote the public health. This work includes developing guidance documents, assisting in maintaining and updating national and international voluntary consensus standards, holding public meetings and publishing safety notices, public health advisories, and other public communications. These efforts began 50 years ago and continue today.