On Monday, May 16th, the FDA issued a final guidance, entitled “Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act.” A draft of the guidance was published on August 16, 2011, and the finalized document replaces FDA’s April 2006 guidance, entitled “Guidance for Industry and FDA Staff; Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act.”
Since it was first established in 1990, section 522 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) has undergone numerous revisions. Because of this, the guidance states that it “will assist manufacturers of devices subject to section 522 postmarket surveillance orders imposed by FDA by providing:
- An overview of section 522 of the Act
- Information on how to fulfill section 522 obligations
- Recommendations on the format, content, and review of postmarket surveillance plan submissions.”
Section 522 of the FD&C Act grants FDA the authority to require manufacturers to conduct postmarket surveillance in various situations, including:
- “A class II or class III device for which failure of the device would be reasonably likely to have a serious adverse health consequence (section 522(a)(1)(A)(i) of the Act).”
- “A class II or class III device expected to have significant use in pediatric populations (section 522(a)(1)(A)(ii) of the Act).”
- “A class II or class III device intended to be implanted in the human body for more than one year (section 522(a)(1)(A)(iii)(I) of the Act).”
- “A class II or class III device intended to be a life-sustaining or life-supporting device used outside of a user facility (section 522(a)(1)(A)(iii)(II) of the Act).”
Pediatric Population Provisions
Manufacturers of class II and III devices that are “expected to have a significant use in pediatric populations” are required to conduct postmarket surveillance. However, FDA notes that this provision is not limited to devices labeled for pediatric use. Rather, the guidance states that “section 522(a)(1)(B) of the Act authorizes the agency to order postmarket surveillance as a condition of clearance or approval for devices expected to have significant use in pediatric populations.”
Section 522 of the FD&C Act does not define “pediatric population.” As such, the guidance document states that “FDA is defining pediatric populations to mean patients who are 21 years of age or younger at the time of diagnosis or treatment, that is, from birth through the twenty-first year of life, up to, but not including the patient’s twenty-second birthday,” which is consistent with the definition provided under section 520(m)(6)(E)(i) of the FD&C Act.
Postmarket Surveillance Duration
“In general, section 522(b)(1) of the Act authorizes FDA to order prospective postmarket surveillance for duration of up to 36 months unless the manufacturer and FDA agree to extend that timeframe or, if there is no agreement, after the completion of a dispute resolution as described in section 562 of the Act.” Nonetheless, the guidance states that devices expected to have significant use in pediatric populations may be subject to a surveillance period of more than 36 months. This is to assess how the device impacts growth, development, activity level, and other factors on the safety or efficacy of the device.
Timing for Issuing a 522 Order
FDA has the authority to issue a postmarket surveillance order at the time that the device receives approval or clearance as well as anytime thereafter. The manufacturer must begin postmarket surveillance within 15 months of receiving the order.
Pre-522 Postmarket Surveillance Process
Identification of Issue
At any point during the life cycle of a device, the FDA may identify issues that are appropriate for postmarket surveillance. These issues may be identified through:
- Analysis of adverse events reports
- Recall or corrective action
- Post-approval data
- Review of premarket data
- Reports from other governmental agencies
- Review of scientific literature
Situations that may raise postmarket questions, during both pre and postmarket periods, include:
- “FDA may order postmarket surveillance to better understand the nature, severity, or frequency of suspected problems reported in adverse event reports or in the published literature.
- FDA may order postmarket surveillance to obtain more information on device performance associated with real-world clinical practice.
- FDA may order postmarket surveillance to address long term or infrequent safety and effectiveness issues for implantable and other devices for which the premarket testing provided more limited information. For example, premarket evaluation of a device may have been based on surrogate markers. Once the device is actually marketed, postmarket surveillance may be appropriate to assess the effectiveness of the device in detecting or treating the disease or condition, rather than the surrogate. Data collected through postmarket surveillance may include rates of malfunction or failure of a device intended for long-term use or incidents of latent sequelae resulting from device use.
- FDA may order postmarket surveillance to better define the association between problems and devices when unexpected or unexplained serious adverse events occur after a device is marketed, if there is a change in the nature of serious adverse events (e.g., severity), or if there is an increase in the frequency of serious adverse events.”
Team Review of Issue
After the Agency has identified a potential issue with a device, the Division of Epidemiology (DEPI), Office of Surveillance and Biometrics (OSB), Center for Devices and Radiological Health (CDRH) will determine if requirements for a 522 order have been met. If they have, the Division will form a team to conduct a more in-depth review the issue. This team may be made up of FDA epidemiologists, clinicians, or other experts as needed to assess the issue. The team will review and evaluate various elements associated with the data. Upon completion of the review, the team will make a recommendation to the DEPI Division Director and OSB Director as to whether or not a 522 order should be issued.
Issuance of Order
“An order for postmarket surveillance under section 522 of the Act will generally be issued by the OSB Director. The 522 order should identify the premarket submission involved (i.e., 510(k), PMA, PDP, or HDE, or de novo petition), the public health questions, the rationale for the 522 order, and postmarket surveillance design recommendations to assist the manufacturer subject to the 522 order in preparing the postmarket surveillance plan.”
Postmarket Surveillance Plans & Reports
In its draft guidance, FDA provides a number of recommendations regarding the development of postmarket surveillance plans and interim and final postmarket surveillance reports. Additional information on the Agency’s requirements is available in our FDA News article, entitled “FDA Finalizes Guidance Containing Postmarket Surveillance Recommendations, Part Two: Postmarket Surveillance Plans & Reports.”