Following several eventful years in Washington D.C., the medical device industry can look to a period of calm in the 2004 regulatory landscape. With the presidential election only months away, it's unlikely any major initiatives will be launched by either the White House or FDA. However, that doesn't mean change isn't forthcoming.
With the Medical Device User Fee and Modernization Act (MDUFMA) of 2002 now in its second full year and the industry growing accustomed to paying for product submissions, interactions with FDA officials, along with expectation of the agency's performance, have shifted. That trend is likely to continue in this age of user fees, especially after large increases were added to the fee schedule last year. Device makers say they expect a return on their investments in the form of shorter review times, which, in turn, would lead to a faster time to market.
In addition to speeding up the agency review process, other changes such as the use of third-party inspections are expected to take place this year. Moreover, FDA officials are working on guidance documents covering a number of issues, including electronic labeling.
Although U.S. device manufacturers place most of their attention on news originating from inside the Beltway, they are also concerned with regulatory development overseas in major markets such as the EU and Japan. As global manufacturers grow overseas sales, they are also becoming more keenly aware of major changes such as the addition of new member states to the EU this year. All of these developments carry weighty regulatory consequences for U.S. device makers selling to those markets.
Changes in Rockville
Perhaps the biggest change at FDA offices such as the Center for Devices and Radiological Health (CDRH), which is located in Rockville, MD, might be one that hasn't appeared on any technical document or regulatory annual report. Some industry observers say the agency in the past has become more cooperative and less adversarial with device manufacturers. That's not to say enforcement has eased or regulations have weakened; instead, communications have opened up and presubmissions meetings are now regular events.
"There certainly is a lot of outreach," said Paul Touhey, president of Fujirebio Diagnostics in Malvern, PA. A U.S. subsidiary of a Japanese diagnostics company, Fujirebio is considered a small device company in the U.S. Touhey said his company others like it have benefited from the change in FDA culture.
How so? For one, he said, there is greater transparency and predictability in the submission process, a change he first noticed about three years ago. A complaint that the industry has voiced for years is that product submissions to the FDA often are delayed or rejected without clear or good reason. More recently, Touhey said, companies can better predict if a submission will be flagged by regulators.
In part, that stems from a greater use of pre-submission meetings, in which regulators discuss the concerns and questions companies may have before they apply for product clearance. Additionally, Touhey said, CDRH following the enactment of the FDA Modernization Act (FDAMA) in 1997 appears to be more interested in helping new medical technology reach consumers. That shift in policy has become very apparent, he added.
Striking a Balance
"I would say three years ago I felt a definite interest in CDRH trying to strike a hard balance to improve public health by approving products more quickly and by protecting public health by not approving them too quickly," he added.
That effort can be seen in some reported data but not all. According to the agency's 2003 annual report issued by its Office of Device Evaluation (ODE) and Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), the average review time for 510(k) decisions fell from 96 days in 2001 to 86 days in 2003; these improvement have been even more dramatic compared with 1999, when the average was 102 days.
On the other hand, average review times for PMA decisions has not changed much. In 1999, the average number of FDA days spent in review was 153; in 2003, it was 151; in 2001 the average was 129.
Those statistics might not fairly depict performance at the agency because the number of trained reviewers in any year might differ. Also, the number of submissions has fluctuated in the past five years.
How much the shifting culture at FDA has benefitted device manufacturers is open to debate, but a number of observers say at the very least, regulators' goals are more aligned with those of industry: to help deliver life-saving technology to the marketplace more quickly.
"They are not the FDA you read about 20 years ago, " said Rebecca Leaper, vice president of quality assurance and business development at Bio-Reg Associates in Beltsville, MD. "I think it's encouraging that they are willing to have an open and supportive dialogue with industry."
Shifting cultures aside, the agency is mandated by MDUFMA to improve its performance goal, and 2003 brought the agency the resources needed to meet those goals. ODE and OIVD added 44 new reviewers and 87 total employees, the largest infusion of labor in about a decade.
For the agency to meet its performance goals specified by MDUFMA, lawmakers will need to continue fully fund the user fee program. Already it has fallen short in the first two years, but President Bush in his FY2005 budget has asked for the necessary funds. Whether the budget will be passed with that amount earmarked for the agency remains to be seen.
As the agency tries to improve review times, it will need to provide even more transparency through guidance documents. Two much-anticipated ones scheduled for release soon will address deficiencies in the original MDUFMA legislation.
Recently the Senate and the House passed the MDUFMA Technical Corrections bill, which fixed language problems that made some portions of the law impractical. For instance, language allowing the establishment of third-party inspections needed to be changed to enable the program to work; also, the bill put into place an 18-month moratorium on requiring device manufacturers to label their names or brands on all devices. This measure gives Congress and the FDA more time to reconsider the requirement to label.
Caspar Uldriks, special assistant to the director in the Office of Compliance at FDA, said the two guidance documents are expected to be released as early as April. They are widely anticipated because they will affect the entire device industry, especially if labeling of all products were mandated.
Uldriks said the reasons that the guidance was held back was Congress' inability to pass the technical corrections bill before the Christmas break last year. The House only recently voted on the bill, which delayed the drafting of the guidance. Although the bill had not been signed into law as of press time, Uldriks said it should be enacted shortly.
The establishment of the third-party inspection program will be a crucial addition to FDA resources. Under the program, accredited parties will be able to perform inspections, which until now had only been performed by FDA personnel. The program aims to speed inspections and allow companies to have the option of paying for third-party participation.
A broader ramification is that the program pushes the industry toward harmonization-the ability to satisfy numerous regulatory agencies with one inspection, although such a goal remains lofty for the device industry. However, some see the program moving the industry closer.
"This is a step toward global harmonization," said David West, vice president of medical devices at regulatory consultant Quintiles in Rockville. 'Third-party inspection is like a building block, a step toward mutual recognition across borders."
West said it's a significant program because accredited bodies that are recognized in numerous jurisdiction can inspect one facility and satisfy many agencies. For device companies, it means fewer intrusions and headaches. It also means adhering to one standard instead of a myriad of them.
According to the FDA, in January 15 accredited organizations were trained to perform inspections. Under MDUFMA, only 15 were allowed in the first year of the program, but additional ones will be eligible to participate in subsequent years.
With training completed, the accredited organizations will have to perform three supervised inspections each before they can be accredited. The first one they must observe an FDA inspection; for the second one they will jointly perform the inspection with an FDA staff member; they perform the last one under observation by an FDA official.
The use of third parties to perform FDA functions is not new. The agency already accepts third-party reviews of submissions. However, that program, which began in 1997 under FDAMA, was slowly embraced by industry and only recently began to gain widespread acceptance. Stakeholders are hoping the third-party inspection program will gain a foothold more quickly.
Paul Brooks, assistant vice president of product services for BSI Management Systems in Reston , VA, said he believes the third-party inspection program will benefit the device industry in the long rung. However, he said there may be problems initially as some accredited bodies try to meet FDA expectations. He added that most likely only the most highly regarded organizations will qualify to be third-party inspectors.
"The bar is pretty high to get recognized in this program," he said. "There could be short-term embarrassments but in the long run this will work."
Another aspect of MDUFMA that will be closely watched by industry later this year is the size of user fee hikes for FY2005. Last year's increase drew many complaints as the fees went up significantly for all product categories. Mark Leahey, executive director of the Medical Device Manufacturers Association, said MDMA members as well as all device manufacturers will be sensitive to any fee increases for next year.
The rates for this year rose 34% for PMA submissions for both small and large manufacturers; however, 510(k) fees rose 59% for regular submissions and 27% for small businesses. The sizable increases were due to a number of factors, including a drop off in the number of submissions, a scheduled fee hike and an adjustment for inflation.
With medical device manufacturing one of few major industries boasting a trade surplus, U.S. manufacturers must increasingly watch regulatory developments overseas. This year, the key issue isn't so much new regulations but the impact of new member states on existing EU regulations, said Ludger Moeller, president of Medical Device Safety Service (MDSS), an authorized representative based in Hannover, Germany. The EU this year will experience its largest influx of new members since it was first formed, with the additions of Cyprus, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, the Slovak Republic and Slovenia.
For device manufacturers, the additions represent both significant market opportunities as well as challenges. CE-marked products are automatically eligible for sale in these new countries; however, manufacturers will also have to label products in local languages. While some countries may decide to allow English, other such as Poland will insist on Polish labeling.
Language requirements may indeed prove a vexing problem for device makers. Serving 25 member states, each with its own adaptation of the EU rules, medical device manufacturers face a growing list of mandates. The labeling requirements of the first 15 countries were tough enough, but the new states will mean more convoluted labels or more versions of the same products. Manufacturers may have to ask distributors to pay for translation of the labeling or rely more on the use of symbols. Another consideration is electronic labeling, although there hasn't been widespread consensus on its use.
One regulatory development that will surely affect one class of device makers is an effort to reclassify total joint replacements, which are currently classified as Class IIb. Moving these devices into Class III would require design reviews as well as meeting other regulatory mandates. While not expected to become a significant market hurdle for manufacturers, it will add regulatory burdens.
The current proposal would give manufacturers of existing products up to two years to comply by providing design dossiers for review by a notified body. New products would undergo the same review process as a Class III products. Moeller said the efforts to reclassify have been ongoing for two years, and it appears the EU is ready to approve the change. While more regulations will be imposed on joint replacement manufacturers, he said they shouldn't experience problems receiving regulatory clearance.
"It's a matter of looking through [the design documents] by a third party," he added.
As medical device manufacturers face an increasing barrage of regulations, the dream of global harmonization may one day become a reality. If that were to happen, uniform standards, mutually recognized audits and other harmonized mandates could help companies more easily comply with regulatory mandates all over the world.