FDA Issues Draft Guidance, Proposed Rule Regarding Submission of Information on Pediatric Use of Medical Devices

By Jennifer D. Newberger –

The Food and Drug Administration Amendments Act of 2007 (“FDAAA”) amended the Federal Food, Drug, and Cosmetic Act (“FDC Act”) to require certain medical device submissions to include, “if readily available – (A) a description of any pediatric subpopulations that suffer from the disease or condition that the device is intended to treat, diagnose, or cure; and (B) the number of affected pediatric patients.”  (See our FDAAA summary and analysis here.)

To implement that requirement, on April 1, 2010, FDA published a proposed rule along with a direct final rule.  FDA ultimately withdrew the direct final rule because it received “significant adverse comment[s].”  After considering the comments, on February 19, 2013, FDA issued a supplemental notice of proposed rulemaking to implement the pediatric submission requirements.  It issued a draft guidance document the same day addressing how industry can comply with those requirements.

One aspect of the proposed rule that resulted in negative comments was FDA’s request for information on “potential” pediatric uses.  The comments noted that requiring information on potential uses was inconsistent with the language of the statute, and would require sponsors to speculate as to possible uses and subpopulations.  FDA agreed, and removed references to potential pediatric uses.

The proposed rule now requires sponsors to include “readily available” pediatric information in any HDE, PMA or PMA supplement, or PDP.  FDA does not interpret 30-day notices to be PMA supplements for purposes of the proposed rule.  Furthermore, it notes that an applicant submitting a PMA supplement need not provide previously submitted information, but may reference the previous application that contained that information.  If new addition has become “readily available” since the prior submission, the PMA supplement must include that information.

The proposed rule defines “readily available” as “available in the public domain through commonly used public resources for conducting biomedical, regulatory, and medical product research.”  The draft guidance expands on this by providing examples, including “bibliographic databases of life sciences and biomedical information (such as MEDLINE and PubMed) and online scientific and medical publishers (such as the Public Library of Science (PLoS) and the Cochrane Library).”

The draft guidance also clearly states that because the submitted pediatric use information will be available to the public as part of the annual report required by FDAAA to be submitted to Congress, the submitted information “should exclude proprietary, trade secret, and commercial confidential information about the device.”

The proposed rule and draft guidance also address the following important issues:

• Pediatric patients are defined as “patients who are 21 years of age or younger (that is, from birth through the 21st year of life, up to but not including the 22d birthday) at the time of the diagnosis or treatment.”
• Pediatric subpopulations include neonates, infants, children, and adolescents, and the draft guidance provides the age ranges included within each subpopulation.
• The information provided should come from a data source that has data only on U.S. subjects.  If there is no readily available information on U.S. subjects, or if the estimate of pediatric patients is considered unreliable, the sponsor may rely on information obtained from data on non-U.S. subjects.  In that case, the sponsor should include a discussion about the applicability of the non-U.S. data to the U.S. patient population.
• If no information about pediatric uses or subpopulations is readily available, the sponsor must indicate that it made a “reasonable effort” to provide the information, and must also provide documentation of the search performed, including the search engines used and key words searched.
• The draft guidance includes a table intended to serve as an example of how the information should be presented.  The table includes information on the approved or proposed device indication; pediatric incidence; pediatric prevalence; pediatric subpopulation/age range; specific device/component; and the source used to identify the information.

Perhaps the question of greatest importance to sponsors is what FDA will do with the pediatric device use information.  According to the draft guidance, “FDA would like to use this data to determine unmet pediatric needs in medical device development.  Once unmet needs are identified, FDA will be better able to coordinate efforts of stakeholders, device manufacturers and FDA staff to promote new device development and proper labeling of existing medical devices for pediatric use.”  It is not clear how FDA will use the pediatric information to meet this noble, if vague, intent.