Medical Device Blog – QA & Regulatory Updates from Emergo Group

The US FDA’s Center for Devices and Radiological Health (CDRH) has launched a 12-week pilot program on its proposed CDRH Network of Experts, a panel of outside scientific experts to provide more specialized knowledge about emerging medical device technologies in order to expedite medical device reviews.

According to the CDRH, the outside panel will only provide information and expertise on particular issues, not actual policy advice. The network would be formed through partnerships with scientific, academic and clinical organizations.

The CDRH Network of Experts plan comprises two standard operating procedure (SOP) documents: the Expert Enrollment SOP covering how collaboration agreements will dictate interactions between outside experts and CDRH staff, and the Expert Utilization SOP governing how staff will engage with outside experts as well as safeguards to address confidential information and conflicts of interest.

The Network of Experts proposal was one of 25 rolled out in early 2011 as part of the FDA’s Plan of Action for Implementation of 510(k) and Science Recommendations intended to boost regulatory predictability and transparency.

The pilot program will last until December 30; CDRH is also seeking public comment through October 28.

The US FDA’s Center for Devices and Radiological Health (CDRH) has issued an update to its Letter to Industry about Import Entry Review Process from March 2011 specifying which Affirmation if Compliance (AofC) codes to use for radiation-emitting medical devices imported into the US market.

Using correct AofC codes can help ensure that medical device imports are not held up for further FDA entry review prior to distribution, marketing and sales in the US, according to the new CDRH letter. Medical device manufacturers as well as their importing and distribution partners shipping radiation-emitting electronic medical devices should adjust their processes accordingly to avoid US market entry delays.

Radiation-emitting electronic products, many of which have medical technology applications, are subject to US federal performance standards and regulated by CDRH, 21 CFR Parts 1000-1005 and US Customs and Border Protection (CBP) regulations 19 CFR 12.91. Such products include video display monitors using cathode ray tubes, diagnostic x-ray systems and components, laser products and ultrasonic therapy systems.

Importers of any radiation-emitting electrical products subject to federal performance standards must submit information for each shipment to both the FDA and CBP, and affirm whether their products comply with performance standards.

Radiation-emitting electronic medical devices subject to federal performance standards must submit appropriate AofC codes listed in the FDA’s March 24, 2011 letter as well as AofC codes applicable to both medical devices and radiation-emitting electrical products provided in the new notice:

Questions regarding AofC codes and the US import entry review process should be addressed to the CDRH Office of Compliance Import/Export Safety Staff: cdrhocimport [at] fda [dot] hhs [dot] gov, with the subject line “EPRC Inquiries.”

New draft guidance from the US Food and Drug Administration recommends compliance pathways for medical device manufacturers regarding post-market surveillance requirements for pediatric products.

 The guidance stems from changes made to Section 522 of the FDA Amendments Act of 2007 that authorize the FDA to order postmarket surveillance periods of longer than 36 months for Class II and III devices with significant pediatric applications; 510(k) clearance or PMA approval of those devices would be contingent upon meeting those postmarket surveillance requirements.

The FDA emphasizes that section 522 postmarket surveillance requirements apply not only to devices labeled for pediatric use, but also devices with off-label pediatric applications. The agency may order postmarket surveillance studies of durations longer than 36 months in instances where a device’s impact on growth and development needs to be assessed.

The FDA’s Center for Devices and Radiological Health (CDRH) has the authority to require postmarket surveillance studies at any point in a device’s lifecycle. The guidance lists several examples of when in the pre- or post-market process the CDRH may order surveillance:

• To confirm the nature, severity or frequency of issues contained in adverse event reports or published literature
• To gain more experience with a change in the device’s use from hospital to home settings, or with new patient populations
• To address long-term or infrequent safety and effectiveness questions regarding implantable devices and other products that premarket testing does not adequately cover
• To better define a device’s problems stemming from unexpected adverse events after that device’s marketing has begun

In the event that the CDRH orders a manufacturer to conduct a postmarket surveillance study, the guidance lists key elements to include in a study plan, including device description and indications for use, study purpose and objectives, design, and timelines. Guidelines for submitting interim and final study reports, as well as content and formatting requirements, are also covered.

A recent audit of the Food and Drug Administration’s 510(k) program by the Center for Devices and Radiological Health (CDRH) has found that inadequate device performance data submissions from sponsors make up a substantial majority--80%--of Not Substantially Equivalent (NSE) determinations made by the agency between 2005 and 2010.

The analysis covered more than 700 NSE determinations made during the course of that six-year period. NSE determinations were based either on failure to provide appropriate performance data to support substantial equivalence (SE) determinations, or to demonstrate equivalent performance compared to predicate devices.

The remaining 20% of NSE determinations between 2005 and 2010 were associated with FDA requests for additional data that had not been made for predicate devices. These requests stemmed from different indications, new technologies or new safety issues associated with devices under review.

A chart comparing percentages of SE, NSE and undefined “other” decisions from 2001 to 2011, however, shows a relatively flat (and low) trend line in terms of actual numbers of NSE determinations over that time period. Only 3.5% of 510(k) submissions earned NSE determinations between 2001 and 2010; that percentage increased to 8% in 2010, but has so far fallen to 5% for 2011. Agency report authors argue that although NSE determinations remain small in number compared to the overall volume of 510(k) applications reviewed, these determinations take up an inordinate amount of resources and should be minimized.

Conducting a more granular analysis of 109 510(k) submissions in 2009, investigators found that NSE determinations stemmed from the following issues:

• For 88% of cases determined to be NSE, the FDA had to conduct additional review cycles because sponsors did not adequately address the agency’s initial questions, or because sponsors’ responses raised additional safety concerns
• For 18% of submissions, the agency requested data that had not been required for those devices’ predicates, due to issues such as safety concerns arising from pre-clinical testing results
• In 16% of cases, data from sponsors indicated their devices performed more poorly than their predicates