Originally Published MDDI November 2003WASHINGTON WRAP-UP Don’t bother mentioning in your 510(k) application a device use other than the intended one. You’ll offend CDRH.James G. Dickinson

James G. Dickinson

November 1, 2003

12 Min Read
How Not to Expand Your 510(k)

Originally Published MDDI November 2003


Don't bother mentioning in your 510(k) application a device use other than the intended one. You'll offend CDRH.

James G. Dickinson

Orthofix to Pay $1.7 Million to Feds | Balloon Catheter Maker Cited by FDA | Boston Scientific Warned about Clinical Trials | Mentor Released from Consent Decree | New X-ray Information Guidance by FDA | FDA Rejects Imaging Diagnostic's PMA  | CDRH Explains Its Faster-Reviews Goals| Wright Medical Cited for ‘Documentation'

Referencing in a 510(k) appendix a device use that is different from the intended one will not expand FDA clearance to cover that second use. This was the message CDRH compliance director Tim Ulatowski sent Philips Medical Systems in an August 8 warning letter just posted to FDA's Web site.

He called the company's use of this technique to make cardiac-perfusion claims for its Intera CV magnetic resonance devices “false and misleading.” Philips's 510(k)s actually covered “use as diagnostic devices that produce transverse, sagittal, coronal, oblique cross-sectional images; [and] spectroscopic images and/or spectra; based upon H and P metabolites and that display the internal structure of the head, body, or extremities” only.

Philips's indications expansion drew CDRH's attention from claims the company made on its Web site, on a link from its home page, and in a commercial brochure entitled “Cardiovascular MR: The Intera Advantage.” 

Ulatowski reminded Philips that it had been under written notice since April 4, 2001, that FDA did not clear its devices for cardiac perfusion. This reminder also addressed a reference in an appendix to one of the company's 510(k)s that “[t]he Cardiac Perfusion Package enables multi-slice first pass cardiac perfusion studies for assessment of cardiac perfusion in rest and stress situations.” Ulatowski said this reference does not mean that the agency cleared the devices for that use.

Warning that the unapproved claims “misbranded” the devices in FDA's view, Ulatowski urged the company to “take prompt action to correct these violations.”

Orthofix to Pay $1.7 Million to Feds

Orthofix International (Huntersville, SC), a provider of medical devices for the orthopedic and trauma markets, has agreed to pay $1.7 million to resolve a two-year federal investigation of its billings to federal and state healthcare programs.

The investigation centered on payments TriCare (formerly CHAMPUS) made to Orthofix for bone-growth stimulators prescribed by physicians to cervical-spine-surgery patients. TriCare is a federal health insurance plan that covers many active-duty and retired servicemen and women and their families.

Although FDA approved the Orthofix bone-growth stimulator products for use on the lower back more than 10 years ago, the company says that because of the products' success when used in the lower back, surgeons commonly prescribe the stimulators off-label to promote healing following surgery on the neck and cervical portion of the spine. However, TriCare does not permit coverage for off-label uses of medical devices, even when a treating physician certifies that the device is an important factor in the success of the spinal surgery. 

Orthofix CEO Charles Federico said company attorneys disagreed with the federal government's interpretation of TriCare coverage for off-label uses of an FDA-approved device, but decided to settle the matter to avoid costs of protracted litigation and to maintain the company's good relationships with government health programs.

Orthofix did not admit any wrongdoing in connection with the settlement, which covers the years 1995 through 2002. The Department of Justice also closed concurrent investigations of the company's billings to Medicare, Medicaid, and other federal health programs without taking further action.

Federico says the company is expanding its line of bone-growth stimulation devices to include a device specifically designed for treatment of the cervical spine. It is seeking FDA approval for its Cervical-Stim Cervical Fusion System. Data from a concluded investigational device evaluation clinical trial will be presented in the fourth and final module of the PMA application for the product, due to be submitted by the end of this month.

Balloon Catheter Maker Cited by FDA

Stafford, TX–based Life-Tech Inc.'s alleged inadequate complaint-handling system and corrective and preventive action (CAPA) procedures provoked FDA to issue a four-page warning letter. A month-long FDA inspection in May and June documented that the company had not thoroughly investigated complaints or collected the information required for reporting adverse events under the medical device reporting regulation, the letter said.

For example, the FDA letter said that Life-Tech had received “a number of complaints alleging that balloons had come off the RPC-9PU catheter body and stayed in the patients when the catheters were removed. Your firm subsequently investigated the returned catheters but failed to document the results of the investigation and possible root causes….”

FDA's inspection also found that the firm failed to establish and maintain required CAPA procedures, including those for investigating and documenting the “cause of nonconformities relating to product, processes, and the quality system.”

When FDA reviewed a Life-Tech recall of its Uropump Tube and Uropump Damping Chamber, the agency found that the company had “failed to determine or document whether the nonsterility problem was caused by packaging seal failures, contamination in the product, or defects in packaging material.”

FDA also cited Life-Tech for failing to establish and maintain the required procedures for rework, including the retesting and re-evaluation of nonconforming product to ensure that the product meets the approved specifications; and for failing to adequately validate the sterilization process. Furthermore, according to FDA, Life-Tech failed to “establish and maintain design plans that describe or reference the design and development activities and define responsibility for implementation.”

FDA said its inspection found that the firm did not obtain and provide FDA with information that was incomplete or missing from MDR submissions filed by user facilities. During July 2001, Life-Tech received a complaint from a nursing home about occurrences of septicemia in three patients using urine collection devices known as “Belly Bags.” FDA's letter charged that the firm “could not determine a possible root cause of this adverse event,” and that its MDR event file “remains incomplete at the time of this inspection.” The firm “failed to provide documentation or document the details explaining why [it] could not obtain the necessary information from the user facility.” FDA specified that the number of phone calls Life-Tech made to the facility, the dates and times, who the company talked to there, what information or records it requested from the user facility, and what statements or records the user facility provided were unrecorded.

Boston Scientific Warned about Clinical Trials

FDA has charged Boston Scientific with failure to “adequately monitor and secure clinical compliance” at two clinical trial sites, according to a recent warning letter. According to the letter, an FDA inspection of the sites earlier this year revealed that Boston Scientific had no records to document corrective action to address “serious protocol deviations and regulatory noncompliance” at the study sites that were reported during periodic clinical monitoring visits and in reports from the firm's designated monitors and clinical investigators.

FDA reminded the company that any “sponsor who discovers that an investigator is not complying with the signed investigator agreement, the investigational plan, the requirements of applicable FDA regulation, or any conditions of approval imposed by FDA or the reviewing Institutional Review Board (IRB), must promptly either secure compliance or discontinue shipments of the device to the investigator and terminate the investigator's participation in the investigation [21 CFR 812.463].”

FDA said that Boston Scientific's study reported numerous instances where study procedures, including laboratory testing, were not performed or followed consistently. “There were no records to indicate prompt compliance by these participating clinical investigators or 
termination of their participation in the clinical investigation,” the warning letter charged.

The FDA inspection also cited Boston Scientific for not ensuring that a clinical site's device accountability records for the device configuration contained all entries found in the sponsor's records, even though the site had been visited frequently by the study monitor, who reported checking the log. Additionally, FDA said Boston Scientific did not submit progress reports to all of the IRBs as required by the agency's regulations, and it failed to report to FDA an IRB's suspension of a clinical investigator.

The warning letter suggested that Boston Scientific use a “clinical trial quality assurance unit to perform independent audits and data verifications of clinical monitors to determine compliance with their standard operating procedures and with FDA regulations.” It noted that the quality unit is not required, but if the company decided to use one, the unit “should be independent of, and separate from, the routine monitoring or quality control functions of the organization.”

Mentor Released from Consent Decree

Mentor Corp.'s improved GMP compliance record has won it a federal court order vacating a 1998 consent decree with FDA over deficiencies in the firm's breast implant manufacturing process. Like most such decrees with FDA, Mentor's had a provision that allowed the firm to petition the court to vacate the agreement if GMP compliance were sustained for five years and if FDA did not object.

According to the Santa Barbara, CA–based firm, FDA recently provided Mentor with a notice that it would not object to the motion, and the U.S. District Court in Dallas, TX, dismissed the case effective September 8.

When the decree was originally entered, FDA said that the “deficiencies in Mentor's manufacturing process have not been shown to result in a significantly increased risk to women who have these breast implants.” However, FDA inspections of Mentor's manufacturing facility found deficiencies in the plant's quality assurance system that could potentially affect the safety and quality of the breast implants, according to the agency. Deficiencies uncovered by FDA investigators included Mentor's failure to validate its manufacturing process and correct and prevent quality problems.

The consent decree established time frames for Mentor to correct the documented deficiencies, and the company met them. While corrections were being made, FDA allowed Mentor to continue distributing its products. The firm also was required to hire an outside expert to evaluate the deficiencies, report corrections to FDA in a timely manner, and perform comprehensive inspections of the manufacturing facility annually for the first four years.

Additionally, the decree contained a provision allowing FDA to order a manufacturing shutdown if Mentor failed to adequately correct the deficiencies or to maintain ongoing compliance, and to assess civil penalties of $10,000 per day if certain time frames were not met.

New X-ray Information Guidance by FDA

Manufacturers should provide assembly, installation, adjustment, and testing (AIAT) information for each certified component used for the controlled production of x-rays, FDA says in a revised guidance. The subject of the guidance is information disclosure by diagnostic x-ray system manufacturers to assemblers.

The revision of a 2001 guidance, Information Disclosure by Manufacturers to Assemblers for Diagnostic X-ray Systems, aims to clarify the scope and terms of information disclosure and to explain cost and software issues. The information disclosure requirements are intended to enable assemblers or other parties to meet federal performance standards. Information should be provided at a cost not to exceed the basic costs of publication and distribution, the guidance suggests. It also explains each term that comprises AIAT.

The guidance can be accessed at www.fda.gov/cdrh/comp/guidance/2619.html.  

FDA Rejects Imaging Diagnostic's PMA 

FDA has told Imaging Diagnostic Systems (IDS) that a PMA for its computed tomography laser mammography (CTLM) system is not approvable. Submitted in June, the PMA was declared deficient by FDA, which said certain undisclosed issues would need to be resolved before it completed its review, according to a Securities and Exchange Commission filing made by the company on August 27.

The device is intended for use as an adjunct to mammography for women who have dense breasts and equivocal mammograms. The company claims the system can provide the radiologist with additional information to guide biopsy recommendations. 

The company said CTLM is the first patented breast-imaging system that uses laser technology and algorithms to create three-dimensional cross-sectional breast images. The device, according to IDS, visualizes the blood supply of tumors without x-ray use and without breast compression. The cross-sectional and 3-D images are then studied by physicians on the display console or may be stored on CD-ROM discs for comparative study, the company said.

Imaging Diagnostic said it will work with FDA to resolve the deficiencies and will amend its PMA at a later date.

CDRH Explains Its Faster-Reviews Goals

FDA's announcement that it planned to reduce PMA review times by 18% (see last month's Washington Wrap- Up) caused so much confusion that the Center for Devices and Radiological Health posted a clarification to its Web site. The original statement said the faster processing would benefit those applications that reach approval, and would cut review times by 30 days for the “fastest 50% of those applications, approved for fiscal years 2005 through 2007.”

In the clarification, FDA identifies “FDA time to 50% approval” as the metric the agency will use to “evaluate the timeliness of premarket reviews.” It defines the phrase as the time between the PMA filing date and the approval date for “half of the applications filed in a fiscal year to reach final approval.”

How does FDA calculate this metric? The agency said it counts the number of PMAs filed in a fiscal year and divides the number by two. The approved PMAs from this number are then ranked in ascending order based on the total elapsed time from filing to approval. FDA then separates the “fastest 50%” from this ranked list and selects the PMA with the highest review time. This time becomes the “FDA time to 50% approval.”

The agency then goes on to calculate a three-year average by using the “FDA time to 50% approval” for each of three fiscal years, then determines the average of these three numbers.

FDA expects to determine if the goal has been met in late FY 2008. It has committed to lower review times by 30 days for applications filed during FY 2005–2007. It will do this using numbers calculated from the three-year average of “FDA time to 50% approval” for FY 1999–2001 as 360 days for expedited PMAs and 320 days for regular PMAs.

Still confused? View the clarification at www.fda.gov/cdrh/mdufma/goalpma.html.

Wright Medical Cited for ‘Documentation'

Arlington, TN–based Wright Medical Group Inc. said in August that it had received and complied with an FDA warning letter that “addressed process documentation related to certain ceramic-hip liner components manufactured prior to February 2002.”

Among the actions requested by the warning letter, Wright said, was “the retrieval of all such unused components from its U.S. distribution system, and physician notification with respect to the limited number of 133 such components previously sold and implanted in the United States.”

The company said it did not expect it would have to take further action. “All ceramic-hip components currently available in Wright's U.S. distribution system have been manufactured to comply with the regulatory requirements referenced by the FDA's letter.” 

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