Originally Published MDDI April 2003

WASHINGTON WRAP-UP

The government gives plenty of lip service to the device center, but does it back up its words with money? Judging by the proposed 2004 budget, the answer is no.

James G. Dickinson

Noncompliant Firms Kill Warning Letter Pilot  | No Extra Fees for Bundling | Grassroots FDA Dialogs Returning | More Modular Submissions?| What to Include in a PMA or PDP | Don't Exempt from 510(k), AdvaMed Says

What one hand gives, the other takes away—and more besides. Such seems to be the post-user-fee financial future of FDA's Center for Devices and Radiological Health (CDRH). This may be a simplistic way of looking at it, but it's the best I can do at interpreting the president's fiscal 2004 budget, presented to Congress in February.

User fees from device makers are projected to reach $29 million next year. Despite this infusion of new funds, the center expects a 2% drop in overall resources (down from $220 million to $216 million).

This comes about from an arcane balancing of appropriations, user fees, and a Bush administration mandate to do more with less. The result simply compounds the effects of a decade of such belt tightening.

The budget notes that although the center has become more efficient, the increasing complexity of medical devices is creating unmet needs. “This request,” the budget notes, “would allow FDA to shore up its device review infrastructure and contribute towards maintaining review performance and update guidance documents for industry.”

Words like “shore up” and “contribute towards maintaining” hardly ring with confidence. In fact, they retreat from FDA Commissioner McClellan's rhetoric in support of strengthening FDA's science base and keeping pace with technological innovation.

McClellan's goals were spelled out in a January 31 internal FDA document, “Improving Innovation in Medical Technology.” Though heavily biased toward drug and biologic review improvements, the document offered some comments on devices. In one table, it noted a worsening medical device review performance between calendar years 2001 and 2002. It also described an ongoing center program:

“In addition to participation in the planned cross-Center continuous improvement/quality management initiatives, CDRH has begun work to implement a ‘quality review' program quarterly to assess the quality of premarket reviews. This effort includes soundness of scientific/regulatory conclusions, consistency, adherence to regulations/policies/SOPs (including least burdensome principles), and effectiveness of review management. As part of a better review system, CDRH plans to improve CDRH Information Technology capability to better handle electronic submissions.”

On the surface, this sounds good. But given the president's anemic budget request and the device center's recent performance statistics, it merely prolongs the center's decade-long burden: Doing more with less.

Noncompliant Firms Kill Warning Letter Pilot

Like the idea of not getting an FDA warning letter that trade competitors can exploit, and instead quietly working things out with the agency? Four years ago, industry persuaded FDA to do just that in an innovative pilot program. Under the program, device makers could avoid warning letters by responding adequately to FDA-483 observations.

Alas, in February FDA announced it had canceled the program as a result of poor subsequent compliance by the companies involved.

“FDA has determined that the pilot has not provided incentives to promptly correct violations,” said the agency. Firms in the program, it said, had no better compliance in follow-up inspections than firms that had received warning letters. 

FDA also said that the pilot did not “optimize resource utilization,” one of its key goals. While the number of timely responses to FDA-483s increased, the quality of those responses suffered. The effect, said FDA, was to reduce “overall field inspectional effectiveness.” Additionally, the agency said, FDA's policy last year of having the Office of Chief Counsel vet all warning letters helped improve the “legal sufficiency” and quality of the letters.


No Extra Fees for Bundling

Bundling device submissions without triggering extra user fees can help both FDA and industry, AdvaMed recently told the agency. In the past, industry has bundled device submissions only when it makes sense for both the applicant and FDA, AdvaMed pointed out.

One example is when the devices involved are part of one overall system. For instance, a group of reagents may be used together on one instrument platform, or a single reagent on multiple instrument platforms. Another example is when devices share certain technical features. This may occur, for instance, when a new component is used with a variety of different devices, such as a new porous coating for a range of implantable orthopedic devices.

In the past, FDA has allowed bundling for certain new device submissions and changes to existing devices. AdvaMed argued that in such cases the practice should continue and user fees be determined accordingly. “For example, although FDA has made clear that 510(k)s are always required when new IVD reagents are introduced on an instrument, the agency has specified that for previously cleared reagents a company may (1) include all reagents offered on the system in one 510(k) submission; or (2) submit the reagents individually or in a group,” the group said. “In addition, FDA has clarified that 510(k)s for new analytes for an existing family of analyzers may be cleared based on the submission of performance data for a single analyzer, if performance on that analyzer is representative of the family. We propose that these and other bundling practices continue without regard to user fees.”

AdvaMed said additional user fees should not be charged when a single review of data is expected. “For instance, very often a manufacturer may make a single packaging or process change that may affect multiple products,” AdvaMed explained. If FDA conducts only one review of the data to approve the change for all products, it makes sense that only one user fee should apply, the group maintained.

Grassroots FDA Dialogs Returning

FDA's Center for Devices and Radiological Health is reviving its once-vibrant collaborative industry-agency “grassroots” dialog program. Consisting of meetings at local sites around the country, the dialogs began nine years ago.

The groups explored industry frustrations with the agency and sparked such reforms as preannounced inspections and annotated FDA-483s. After FDA associate commissioner for regulatory affairs Ron Chesemore retired two years ago, however, the dialog concept fell into disuse.

President and CEO of Logan, Utah–based Wescor Inc., Wayne K. Barlow was a lead player in the original grassroots effort. He says that CDRH director David Feigal and ombudsman Les Weinstein have promised that they will revive the program. A dialog was held last November; at press time another is slated for April, in either Salt Lake City or Minneapolis.

More Modular Submissions?

FDA should allow modular submissions for other PMA-type submissions, AdvaMed told the agency in recent comments. Currently, FDA limits the special review program to original PMA applications.

In its comments to FDA, AdvaMed recommended that the modular program include panel-track supplements and certain 180-day supplements. It said that modular review “should be permitted for supplements containing clinical data where the expected duration of the clinical trial is sufficient to allow reasonable time for the submission and closure of preclinical modules.”

AdvaMed also said that the agency's performance goals for reviewing modular submissions should be revised. FDA's current policy is to review and close submitted modules within 90 days when the information supplied is complete. However, when data are missing and FDA requests more from the sponsor, AdvaMed asked that the request be made within 75 days of the module's filing. 

The group also said that user fees should not apply to modular submissions turned in before the October 1, 2002, which is the effective date of the Medical Device User Fee and Modernization Act. “Further, the submission of subsequent modules [should] not trigger fees under the Act any more than the submission of an amendment to a PMA received by FDA before October 1, 2002,” AdvaMed argued.

What to Include in a PMA or PDP

FDA has released a guidance to help clarify what information should be presented in certain PMA or product development protocol applications. The types of information described include a device description, preclinical and clinical data, and labeling information. The guidance document may also be useful in preparing an investigational device exemption (IDE), a reclassification petition, or a master access file, FDA adds. 

Entitled Guidance for Saline, Silicone Gel, and Alternative Breast Implants; Guidance for Industry and FDA, the document updates information given in an August 13, 2001, guidance. It is based, FDA says, on the agency's review of additional breast implant applications and discussions with industry.

According to the updated guidance, the following information should be included in a submission involving breast implants:

• A written description of each component that makes up the implant (e.g., shell, gel, patch, textured surface, valve).
• The specific materials and suppliers for each component.
• A description of any connector systems, fill tubes, or wand injection domes, including materials. 
• Magnified implant sketches that depict the placement or use of the connector systems, fill tubes, and injection domes. 
• A description of when the implant is filled by the surgeon, if it is not a prefilled implant (i.e., intraoperatively or postoperatively). 
• A description of any filler material overexpansion or overfill, even if it happens on a temporary basis. 
• A description of the method by which the implant is sterilized.
• A summary table of all implants under review. 

Depending on the implant's particular design, additional descriptive information may be necessary, the guidance notes. To view the guidance, visit www.fda.gov/cdrh/ode/guidance/1354.pdf. 

Don't Exempt from 510(k), AdvaMed Says

FDA should not continue to exempt from 510(k) clearance certain reprocessed devices, says AdvaMed. The devices named include disposable arthroscopic surgery blades and burrs, non-electric biopsy forceps, ureteral stone dislodgers, and sagittal saw blades. The trade group said these types of devices and several others should be required to obtain 510(k) clearance owing to concerns about their sterilization and performance after reprocessing.

Under the Medical Device User Fee and Modernization Act of 2002, FDA is required to review such exemptions. It must determine by April 26, 2003, which exemptions will be terminated. In its recommendations, AdvaMed said: “In general, single-use devices that are reprocessed pose risks of cross-infection, cross-contamination, and impaired performance if they are not properly cleaned and resterilized and capable of withstanding the stress of repeated uses.” 

Copyright ©2003 Medical Device & Diagnostic Industry