Digital mammography systems are on the verge of being downclassified to 510(k) status, but imaging firms say the clinical trial requirements proposed in FDA's draft "special controls" guidance for the systems are costly, unnecessary and overly burdensome.

Full-field digital mammography (FFDM) systems capture full digital x-ray images of the breast, and offer an alternative diagnostic and screening tool to conventional film screen mammography.

FFDM systems may include software, digital image receptors, acquisition workstations and signal analysis programs. Other types of mammographic x-ray producing equipment, such as x-ray generators or breast compression systems, are already regulated as Class II devices requiring only 510(k) clearance before going to market.

Two years after an FDA radiological devices advisory panel unanimously recommended moving the digital systems to the lower-risk category, FDA on May 30 issued a proposed reclassification rule and draft special controls guidance (¹ Also see "FDA Reclassifications In Brief" - Medtech Insight, 2 June, 2008., p. 5).

The advisory panel based its decision on the results of a large clinical trial showing no difference between digital and film mammography in detecting breast cancer in the general population, and a potential benefit for digital mammography in women with dense breasts or women under 50.

The Digital Mammographic Imaging Screening Trial (DMIST) ultimately enrolled nearly 50,000 women and tested four different digital mammography systems.

FDA says it finally understands the devices well enough to develop appropriate special controls to mitigate foreseeable risks.

While other imaging systems have long been regulated as Class II devices, extra care is required with breast mammography, FDA says, because the technology is used to screen the broader population for cancer, not just to diagnose suspected disease.

When digital systems first emerged, "there were a lot of questions of whether or not cancers were going to be missed, or whether there would be more work-up of the patients," Kyle Myers of FDA's Office of Science and Engineering Laboratories said in an interview.

"We make recommendations that all women over 50 get screened," she said. "We're talking about a lot of women every year, and that's why our concern was high."

Once the rule and guidance are finalized, digital mammography systems will be able to enter the market via the less onerous 510(k) pathway versus the PMA process - though they will have to adhere to the special controls outlined in the guidance. Comments on both documents were due by Aug. 28.

Clinical Trial Requirements Come As A Shock

Device firms agree that downclassification is long overdue, but some of the clinical study recommendations in the draft guidance caught companies by surprise.

According to FDA, the main risks identified with FFDM systems are electrical hazards, corrupted or non-diagnostic images, incorrect patient positioning, excessive x-ray exposure, excessive breast compression and infection or skin irritation.

Most risks can be mitigated with electrical safety evaluation, bench or animal testing and product labeling, but in some cases, more robust clinical data will be needed, FDA says.

A 510(k) submission will probably require clinical data if a system has a different indication than the marketed device it is being compared to, or a dissimilar design or technology, the guidance states.

A features analysis, performed by certified radiologists using both digital and film systems, and including stress testing on some of the most challenging patients, may substitute for a larger clinical trial, the guidance says.

But FDA may still recommend "multi-reader, multi-case" studies when the sensitivity and specificity of a new system is in doubt.

These studies "have no role in a 510(k) application given the results included with previous PMA applications for FFDM systems" and the results of DMIST, the Medical Imaging and Technology Alliance (MITA) writes in Aug. 28 comments.

Additional clinical trials were never discussed or recommended by the FDA advisory panel, adds x-ray technology firm Bioptics in Aug. 25 comments.

The American College of Radiology says the guidance could discourage competition and innovation in the industry. Also, the suggested features analysis and clinical studies would unnecessarily expose patients to double doses of radiation to compare digital and film images, ACR argues.

ACR wants FDA to clarify that multi-reader, multi-case studies will be required only for devices that are not substantially equivalent to predicate devices, such as for the three reasons FDA listed: dissimilar indication, design or technology.

The group says the final guidance should eliminate stress testing as part of the features analysis, or at least specify the maximum number of cases needed to meet FDA's expectations. As it stands, the guidance leaves too much to FDA's discretion, said James Thrall, chair of ACR's board of chancellors and chief radiologist at Massachusetts General Hospital.

"We would like to see as many overarching principles be put in place, assuming that they are reasonable, versus having this more open-ended situation," Thrall said in an interview.

FDA says the 510(k) data requirements will depend heavily on the types of detectors used in new systems.

"We expect that if most systems come along looking much like the ones we've already approved, then we wouldn't expect anywhere near the trials we've required to this point," FDA's Myers told "The Gray Sheet."

If a firm came out with a "very new" detector material, that would require more studies, she said. The main questions are: "Are there new technical concerns? Are there new safety concerns?"

Guidance Disadvantages Smaller Firms

At present the digital mammography market is dominated by a few large corporations.

Women's health firm Hologic, maker of the Selenia digital mammography system, controls 55%-60% of the U.S. market, followed by GE Healthcare ( Senographe ), Fujifilm ( Fuji Computed Radiography for Mammography ), and Siemens ( Mammomat ), according to JP Morgan analyst Tycho Peterson.

Downclassification could open up the field to newcomers, but not if the 510(k) process seems burdensome and expensive, said the American College of Radiology's Thrall.

That view is shared by Fischer Medical Technologies, a small firm that purchased Fischer Imaging's remaining x-ray business after the company sold off its mammography assets to Hologic.

In Aug. 28 comments, the company said it may "wish to enter the FFDM screening market in the future," but would be unable to finance clinical studies to definitively prove the medical efficacy of a new device.

"Now that there are four major players, small companies are not going to finance huge studies and compete in that market," Fischer Medical Technologies President Ronald Shores predicted.

Small firms are often the source of new innovations, he said, and there are still advances to be made. Next-generation digital mammography imaging systems in development include three-dimensional breast computed tomography (CT) scans and breast tomosynthesis.

FDA, too, has begun researching this "new wave" of breast imaging technology. Whether the next-gen systems will require 510(k)s or PMAs will depend on the complexity of the technology and what claims companies make, FDA's Myers said.

"The best thing to do is set up a pre-IDE meeting" with FDA, she advised.

- Jessica Bylander (j.bylander@elsevier.com)

Digital Mammography Firms Decry Clinical Trial Provisions In Draft Guidance

More from Archive

More from Medtech Insight