New Legislation Requires Submission to FDA of Serious Adverse Event Reports (SAERs) for Dietary Supplements and Over-the-Counter (OTC) Drug Products

Date: Feb 15, 2007

President Bush has signed the "Dietary Supplement and Nonprescription Drug Consumer Protection Act," adding new sections 760 and 761 to the Federal Food, Drug, and Cosmetic Act (FDC Act). When this legislation takes effect on December 22, 2007, it will require "responsible persons" to submit to the Food and Drug Administration (FDA) "serious adverse event reports" (SAERs) received for finished nonprescription (i.e., over-the-counter (OTC)) drug products and dietary supplements, along with a copy of the product's label. Nothing would prevent the voluntary submission of adverse event reports (AERs) that do not rise to the level of being "serious."

Products labeled on or after December 22, 2007, will need to include a domestic address or domestic phone number through which the responsible person can receive reports of adverse events. Products that do not include such information (including those imported from foreign manufacturers) will be deemed to be "misbranded" and subject to regulatory action by FDA. Records of all adverse events (whether serious or not) will need to be kept for six (6) years and made available for review by FDA. Congress has also taken steps to ensure that any State or local AER systems are consistent with the new Federal requirements. In addition, the submission of an AER is specifically prohibited from being construed as an admission that the product involved caused or contributed to the adverse event.

The new AER systems will require companies to develop and implement new systems to monitor adverse events and determine which ones must be submitted to FDA. Within 270 days, the Agency is required to issue guidance on the minimum data elements to be included in an SAER, although FDA is likely to provide guidance on other aspects of the requirements as well. The major dietary supplement and OTC drug trade associations strongly supported the legislation, since it is expected to increase consumer confidence in the safety of these products (and dietary supplements in particular) by providing FDA with the means to monitor potential health risks associated with their use. The new requirements are discussed in more detail below.

  1. Detailed Discussion of Requirements

    The new legislation (Pub. L. No. 109-462) added several provisions to the FDC Act to establish parallel, mandatory AER requirements for finished dietary supplements and nonprescription drugs that are subject to FDA's OTC drug "monograph" system. Since the reporting provisions are identical, dietary supplements and OTC drugs will be referred to collectively as "Covered Products" in the remainder of this memo.

    1. Changes to Covered Product Labels

      The label applied to any Covered Product on or after December 22, 2007 (i.e., one year after enactment of the legislation) must include a domestic address or domestic telephone number through which the "responsible person" (discussed below) can receive information about a serious adverse event with the Covered Product. The failure to include such an address or telephone number will cause the Covered Product to be "misbranded" and potentially subject to enforcement action by FDA. New FDC Act §§ 502(x) and 403(y); Pub. L. No. 109-462, Sections 2(e)(2) and 3(d)(2). This provision applies to products imported from foreign manufacturers as well as those produced domestically, and may require that Covered Product labels be revised to include new contact information. The Senate report accompanying the legislation states that companies may, but are not required to, include an email address on the Covered Product label to allow the electronic submission of adverse event information to the responsible person, in addition to the required domestic address or domestic telephone number. Senate Report No. 109-324, at 9.
    2. What Must be Reported and by Whom

      The reporting obligation turns on the difference between an "adverse event" and a "serious adverse event." An "adverse event" is "any health-related event associated with the use of [a Covered Product] that is adverse." New FDC Act §§ 760(a)(1) and 761(a)(1). In the context of OTC drugs, the following are examples of "adverse events": (A) an event occurring from an overdose of the drug, whether accidental or intentional; (B) an event occurring from abuse of the drug; (C) an event occurring from withdrawal from the drug; and (D) any failure of expected pharmacological action of the drug. New FDC Act § 760(a)(1).

      A "serious adverse event" is an adverse event that (A) results in (i) death; (ii) a life-threatening experience; (iii) inpatient hospitalization; (iv) a persistent or significant disability or incapacity; or (v) a congenital anomaly or birth defect; or (B) requires, based on reasonable medical judgment, a medical or surgical intervention to prevent an outcome described in clause (A). New FDC Act §§ 760(a)(3) and 761(a)(2). The Senate report accompanying the legislation acknowledged that many responsible parties may not have the medical expertise needed to determine whether a particular adverse event is "serious." In those cases, the responsible parties may contract with a third party with greater medical expertise, but the "responsible person" named on the product label "still maintains ultimate responsibility for reporting under the law." Senate Report No. 109-324, at 8.

      A "responsible person" is required to submit to FDA SAERs associated with a Covered Product when used in the United States (although nothing prohibits the voluntary submission of AERs that are not "serious"). Information on adverse events occurring outside the U.S. need not be reported to FDA, even if they are "serious." The new legislation defines the "responsible person" as the manufacturer, packer, or distributor whose name is required to appear on the label of a Covered Product marketed in the United States, under sections 502(b)(1) or 403(e)(1) of the FDC Act. New FDC Act §§ 760(b)(1) and 761(b)(1).

    3. Time Frames for SAERs

      SAERs must be submitted to FDA, along with a copy of the label of the Covered Product involved, within 15 business days after the responsible person receives the information through the address or phone number on the label of the Covered Product. New FDC Act §§ 760(c)(1) and 761(c)(1). Responsible persons also have an obligation to provide to FDA any new medical information associated with a previously-submitted SAER that is received from the original reporting party within one (1) year after the initial report. However, it does not appear that the responsible person has an obligation to seek out additional information about an adverse event or report information from sources other than the original reporting party. This supplemental information is to be submitted within 15 business days of receipt by the responsible person.

      Each SAER is to be submitted through FDA's MedWatch program. Although the legislation does not specifically indicate, it is expected that submitters will use form FDA 3500A (for mandatory reporting). Additional information about the MedWatch program, including copies of form FDA 3500A and instructions for completing it, can be found at the following link. http://www.fda.gov/medwatch/report/mfg.htm. FDA is authorized to modify the MedWatch form to address the Covered Products. New FDC Act §§ 760(d) and 761(d). Since neither dietary supplements nor OTC drugs are described on form FDA 3500A, it is reasonable to expect that FDA will amend the form in the future, although this is unlikely to occur before the mandatory reporting obligation goes into effect.

    4. Obligation to Keep Records; FDA Authority to Access

      In addition to submitting SAERs, the responsible person must maintain records related to each report of an adverse event (whether serious or not) for six (6) years. New FDC Act §§ 760(e)(1) and 761(e)(1). "These records must be maintained regardless of the source of the report, and regardless of any determination by the responsible person that the adverse event was caused by, or associated with, the product." Senate Report No. 109-324, at 10. FDA is specifically authorized to have access to these records during an inspection conducted pursuant to FDC Act § 704. New FDC Act §§ 760(e)(2)(A) and 761(e)(2)(A).
    5. Retailers/Private Label Distributors

      A retailer that does not distribute products under its own name has no AER reporting obligation under this legislation. Retailers that distribute Covered Products under their own name (i.e., as a "private label" brand) represent a special situation. The new legislation allows such retailers, if they so desire, to contract to have the manufacturer or packer of the Covered Product submit the SAERs to FDA. New FDC Act §§ 760(b)(2) and 761(b)(2). In that case, the retailer will be required to convey to the manufacturer or packer all of the AERs reported to the retailer through the address or telephone number on the Covered Product's label. If the retailer assigns the reporting responsibility to another party, that party would be deemed the "responsible person" for purposes of SAER reporting and maintaining records of all AERs. However, it appears from the legislation that the retailer must still be the party to receive the adverse event information through domestic address or phone number on the Covered Product's label. This may be an area that FDA will clarify in its upcoming guidance.
    6. Disclaimer Statements; Preemption of Different Reporting Systems; Use of Reports

      The new legislation specifically provides that the submission of an SAER or a voluntary AER "shall not be construed as an admission that the [Covered Product] involved caused or contributed to the adverse event." New FDC Act §§ 760(g) and 761(g). Any SAER or AER may specifically include a statement denying that "the report or the records constitute an admission that the [Covered Product] involved caused or contributed to the adverse event." New FDC Act §§ 760(f)(1) and 761(f)(1). As a practical matter, any company submitting an AER to FDA should always include such a statement.

      The new legislation also includes a preemption provision which prohibits any State or local government from "establish[ing] or continu[ing] in effect any law, regulation, order, or other requirement, related to a mandatory system for [AERs for Covered Products], that is different from, in addition to, or not otherwise identical to," the new Federal requirements. New FDC Act §§ 760(h)(1) and 761(h)(1). Prior to the enactment of the new AER legislation, several States had proposed implementing their own AER systems. Given the potential concerns about the burden of complying with several different AER systems in the future, the preemption section eliminates that possibility.

      FDA may share AERs and related information with appropriate State and/or local health officials, provided that "personally identifiable information" is not released. In addition, State and local governments are prohibited from using any AER information received from FDA in a manner that construes the report as an admission that the Covered Product caused or contributed to the adverse event. New FDC Act §§ 760(h)(2)(C) and 761(h)(2)(C).

    7. Additional Points

      As noted above, the new AER provisions become effective one (1) year after the enactment of the legislation (i.e., on December 22, 2007). The domestic address/domestic phone number requirements will apply only to those products labeled on or after that date. FDA is required to publish guidance on the minimum data elements to be included in an SAER within 270 days after the date of the enactment, although the Agency is likely to provide guidance on other aspects of the requirements as well. For its part, FDA is required to develop systems to ensure that duplicate reports of, and new medical information related to, an SAER are consolidated into a single report. FDA is also authorized to develop regulations providing exemptions from the AER requirements in appropriate cases.
  2. Conclusion

    Overall, the new AER legislation will impose additional burdens on manufacturers, packers, and/or distributors of OTC drugs and dietary supplements. Companies will need to develop and implement appropriate procedures, train personnel, and/or determine whether they wish to contract out some part of the AER review process. Responsible persons will need to determine what domestic address and/or phone number will be used to receive adverse event information. Since products labeled after December 22, 2007, will need to include this information, affected companies likely will need to make decisions in the relatively near future to make certain that compliant labels are ready for use by the deadline.

For further information about this issue or FDA's regulation of OTC drugs and dietary supplements generally, please contact Frederick A. Stearns at 202-434-4288 or via e-mail at stearns@khlaw.com.