Originally Published MDDI June 2003
Last year's medical device legislation mandates that all medical devices bear the names of their manufacturers. AdvaMed argues that this provision was intended to apply only to reprocessed devices.
James G. Dickinson
Are Illegal Imports OK for Diagnostics? | AdvaMed Writes Ethics Code for Dealing with Doctors |FDA Worries about Bone Cement Labeling | Gynecare Intergel Withdrawn from Market | New Guidance on Natural Rubber Latex | FDA Explains Electronic Labeling Rule
Must all medical devices bear the name of their original maker? In comments made to FDA in March, industry group AdvaMed answered with an emphatic no.
The problem stems from last year's medical device law. According to section 301 of the Medical Device User Fee and Modernization Act (MDUFMA), any device that does not identify its manufacturer will be deemed misbranded. AdvaMed contends that the rule should apply only to single-use devices that have been reprocessed. The original intent of section 301, AdvaMed wrote, “was to avoid confusion on the part of end-users by providing information about the original manufacturer” of the reprocessed single-use product. But the language was later broadened “to include all device products, thus creating unforeseen difficulties for regulated persons and the agency.”
The law allows FDA to exempt devices from this provision. AdvaMed gave a number of reasons why many devices should be exempt:
• Many medical devices are too small to include a manufacturer's name, abbreviation, or symbol.
• The geometry of some devices (e.g., small bone screws) does not afford sufficient space to fit a name, abbreviation, or symbol.
• Name placement may affect device safety and efficacy by imparting stress risers (surface discontinuities where imposed stress can be relieved) to the device.
• The surface properties of some devices (e.g., meshes, sponges, and nasal packing materials) may not allow for legible name, abbreviation, or symbol display.
While the provision allows such markings to be included on product attachments, the group notes that, in many cases, an attachment to a medical device may interfere with use, rendering the product unsafe or ineffective.
AdvaMed also stressed the importance of understanding exactly what constitutes a “manufacturer.” The group recommended that “FDA define the term ‘manufacturer' broadly.” The goal should be to “ensure that end-users are able to accurately identify the person who placed a device into interstate commerce and took responsibility for it.”
This section of the law will become effective in April 2004. AdvaMed said it would be impossible for companies to comply. First, according to AdvaMed, each device type will need to be assessed “to determine the most cost-effective approach for adding the manufacturer's name.” Second, biocompatibility and functionality testing may be needed to ensure that adding the name will not affect device safety or performance. Third, companies will need more time to add extra steps in the manufacturing process to ensure products are properly labeled. Finally, more time will be required “to exhaust current inventory that is not branded with the manufacturer's name.” For these reasons, AdvaMed asked FDA to grant manufacturers “at least a 12-month extension beyond the current deadline.”
The costs to be incurred by industry from the MDUFMA provision are not fully known, said AdvaMed. The group recommends that manufacturers evaluate how this requirement will affect their own costs.
Are Illegal Imports OK for Diagnostics?
FDA has mounted a high-profile enforcement campaign against commercialized imports of low-price Canadian prescription drugs to U.S. consumers. But, according to one company, it is turning a blind eye to comparable trafficking in Canadian diagnostics.
In 1997, FDA stopped Michigan importer Troy Biologicals Inc. from selling Canadian-made Bayer Multistix reagent strips. So concerned was FDA, says Troy CEO Robert Ricketts, that its Office of Criminal Investigations raided his facility with 10 armed agents. The agency impounded his inventory and secured a settlement agreement ordering disposal of all imported strips that were still outside the country.
The issue, he says, was the Canadian labeling that came with the strips. The Canadian label shows both U.S. and Canadian calibrations. The FDA-approved U.S. labeling shows only U.S. calibrations. The difference could confuse users, FDA held.
The settlement agreement left Ricketts saddled with huge legal expenses. Then it was followed by warnings from FDA officials that resuming imports would be at Ricketts's own risk. This so intimidated him, he says, that he has been afraid to do so. As a result, Troy has forgone nearly half a million dollars in estimated revenues. (The reagents business, legal and illegal, has been estimated at $1 billion annually.)
Since the settlement agreement, however, up to 10 competitors have continued to import and ship the same Canadian products without FDA interference, Ricketts says. For seven years, he has filed trade complaints and provided explicit documentation of his competitors' activities to FDA. Yet the agency has taken no action.
As recently as last March, Ricketts says, FDA's Steven Gutman told him that after passage of the FDA Modernization Act in 1997, “I doubt that we would have taken the same position” against his competitors as the agency took against Troy. Gutman is director of the CDRH Office of In Vitro Diagnostic Device Evaluation and Safety. Ricketts says Gutman added that he had looked at all the documentation Ricketts had sent him, but said that his hands were tied.
Gutman, who Ricketts said had been the most helpful FDA person he had yet dealt with, told me he could not comment on Ricketts's allegations. I also asked FDA senior associate commissioner for policy and planning William K. Hubbard about the apparent disparity between the agency's policies for commercialized imports of unapproved Canadian drugs and diagnostics. He said he was not familiar with the issue but would ask his deputy, Tom McGinnis, to “look into it and advise the press office of the facts.” It was Hubbard who formulated the current policy against commercialized imports of foreign prescription drugs for U.S. consumers.
In due course, FDA's press office issued this statement:
Overall we cannot comment on this matter since it is something the agency is currently looking into. However, we would like to put the statements attributed to Dr. Gutman in the proper context. In his conversation with Dr. Ricketts, Dr. Gutman's quote (“I doubt we would have taken the same position”) was based on Dr. Ricketts's assertion that there was no public health risk involved in this matter. Dr. Gutman himself never stated that he shared this assertion.
With regards to the “my hands are tied” quote, Dr. Gutman was merely pointing out that the matter was before the entire agency—again, he did not state that he shared Dr. Ricketts's conclusions.
AdvaMed Writes Ethics Code for Dealing with Doctors
Following the lead of its main drug industry counterpart, the leading device industry trade group is adopting a new “Code of Ethics on Interactions with Health Care Professionals.” The code was approved by AdvaMed on March 20. It will provide manufacturers “a road map for proper interactions with their partners in the healthcare community,” said AdvaMed president Pamela Bailey.
To allow time for training, the code will not become effective until after September 1. Additional information and communication packages will be available from AdvaMed shortly.
FDA Worries about Bone Cement Labeling
Current bone cement labeling does not address its use in treating spinal compression fractures, nor does it address possible complications associated with this use. So wrote FDA's CDRH in an April 1 update to its bone cement public health notification.
Over the past decade, the center reported, several complications have been reported in medical literature and to FDA following the use of polymethyl methacrylate (acrylic) bone cements to treat spinal compression fractures. Complications include serious injuries and deaths. Those relating specifically to bone cement leakage include soft tissue damage and nerve root pain and compression. Other reported complications include pulmonary embolism, respiratory and cardiac failure, abdominal intrusions/ileus, and death.
Each of these complication types, CDRH said, has been reported in conjunction with bone cement use in both vertebroplasty and kyphoplasty procedures. These two different techniques employ the cement to treat spinal compression fractures. There is not enough information, the center said, to establish overall complication rates for either procedure. Likewise, the data are insufficient to distinguish the types and incidence of complications associated with bone cement use in each procedure type.
Guidance on bone cement use in treating spinal compression fractures is offered in the literature and by professional groups. Subjects addressed include patient selection, treatment techniques, potential complications, and patient monitoring. In the absence of labeling on the topic, CDRH urges physicians to consult these sources.
To read CDRH's update, visit www.fda.gov/cdrh/safety/bonecement.html.
Gynecare Intergel Withdrawn from Market
Gynecare has suspended global marketing and sales of Lifecore Biomedical's ferric hyaluronan adhesion prevention product, Gynecare Intergel. It is withdrawing the product from the market to assess adverse-event information obtained from postmarketing experience with the device. Approved for open gynecologic surgery, Intergel was the first product to go before FDA's new dispute resolution panel.
Lifecore said the assessment will include a review of technical issues, surgical techniques, and circumstances associated with the postmarketing events, including reports involving off-label use. “There were two deaths,” according to Lifecore spokesman Jim Bracke, “but they were not attributed to the product. They were attributed to bulb perforations. Otherwise, it's pretty much just the general gamut of pain and inflammation.” Bracke said there are more events that will be assessed, but felt it was “not appropriate” to reveal them.
Since the product's launch in August of 1998 until this past February, the company said, the worldwide complaint rate has been at 0.29% of units sold. Intergel's contribution to these events is unknown, however. The company said the product will return to the market after the review is completed and appropriate action is taken.
New Guidance on Natural Rubber Latex
A new compliance guidance will help makers of medical products that contain natural rubber latex, most of whom are small businesses. It is entitled User Labeling for Devices That Contain Natural Rubber (21 CFR 801.437); Small Entity Compliance Guide.
According to the guidance, FDA had noted an increase in reported deaths associated with sensitivity to natural latex proteins in medical devices. The agency said its initial focus involved deaths following barium enema procedures that were associated with anaphylactic reactions to the natural rubber latex cuff used on barium enema catheter tips.
To reduce the risks associated with sensitivity, FDA developed a regulation requiring that labeling give information to people sensitive to natural latex proteins. This rule was published in a September 1997 Federal Register notice and codified in Title 21 of the Code of Federal Regulations (21 CFR 801.437). It became effective a year later.
The FDA guidance identifies labeling statements for use on medical devices and device packaging when they contain natural rubber that contacts humans. The wording required depends on the product. For devices that contain natural rubber latex that contacts humans, the statement should read, “Caution: This Product Contains Natural Rubber Latex Which May Cause Allergic Reactions.” For devices that contain dry natural rubber that contacts humans, it should read, “This Product Contains Dry Natural Rubber.” Similar wording is required for packaging. The guidance also notes that no product containing natural rubber should be labeled hypoallergenic. To read the guidance, visit www.fda.gov/cdrh/comp/guidance/1212.html.
FDA Explains Electronic Labeling Rule
A new Blue Book memorandum explains to CDRH staff how to implement the electronic labeling provisions of MDUFMA (Sec. 206). The memo was issued by Daniel Schultz, director of the Office of Device Evaluation (ODE), and Steven Gutman, director of the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD). In it, they say distributors of prescription devices who intend them to be used only within a healthcare facility may provide the labeling solely in electronic form. However, they must allow users to request labeling in paper form and promptly provide it without additional cost.
This change in requirements will have direct and indirect consequences that will immediately affect ODE and OIVD, Schultz and Gutman wrote.
First, scientific reviewers may prefer to access and review electronic labeling for certain devices when given the opportunity to do so. Device companies should continue to provide paper labeling in all premarket submissions. Sometimes, however, submissions can also include or reference electronic labeling that is intended to be provided to purchasers.
Second, many devices can be configured to connect directly with personal computers and the Internet. To some extent, however, “FDA labeling expectations” may have discouraged this trend. The change in law, the directors wrote, may result in an increase in such designs.
To read the memorandum, visit www.fda.gov/cdrh/mdufma/bluebook/g03-1.html.
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