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January 27, 2011

Jackson Signs Proposed Rule Amending Human Subjects Protections Rule

Bergeson & Campbell, P.C.

On January 18, 2011, U.S. Environmental Protection Agency (EPA) Administrator Lisa Jackson signed a proposed rule that would revise EPA’s February 6, 2006, final rule concerning protections for subjects in human research. According to EPA, the proposed amendments would broaden the applicability of the rules to cover human testing with pesticides submitted to EPA under any regulatory statute it administers. The proposed amendments would also disallow participation in third-party pesticide studies by subjects who cannot consent for themselves. Finally, the proposed amendments would identify specific considerations to be addressed in EPA science and ethics reviews of proposed and completed human research with pesticides, drawn from the recommendations of the National Academy of Sciences (NAS). The pre-publication version of the proposed rule, which EPA expects to publish in early February 2011, is available online. Comments will be due 60 days after EPA publishes the proposed rule in the Federal Register.

EPA states that, in seeking comments on the proposed amendments, “EPA does not imply that the current Federal Policy for the Protection of Human Subjects (the “Common Rule”)… is inadequate,” and, in fact, “the amendments proposed here would make no changes to the Common Rule or EPA’s codification of the Common Rule.” The proposed amendments are the result of EPA’s 2010 settlement of a lawsuit brought by Natural Resources Defense Council (NRDC), Pesticide Action Network North America, Pineros y Campesinos Unidos Del Noroeste, Physicians for Social Responsibility – San Francisco, Farm Labor Organizing Committee, AFL-CIO, and Migrant Clinicians Network. The petitioners sued EPA in 2006, claiming that the final rule violated language in the fiscal year 2006 appropriations bill, in which Congress asked EPA to incorporate the Nuremberg Code on medical experiments and recommendations from NAS into the rule, as well as a restriction on testing on pregnant women and children. The settlement includes language intended to close a “loophole” that petitioners claimed allowed some tests to be conducted on pregnant women and children, would eliminate a provision that allowed an “authorized representative” to consent to the testing on behalf of a subject, and would require human testing to adhere to a set of scientific and ethical standards based on the NAS recommendations. Under the settlement, EPA agreed to propose negotiated amendments by January 18, 2011, and to promulgate a final rule byDecember 18, 2011.

In its proposed rule, EPA notes that the settlement agreement “make[s] clear that EPA retains full discretion concerning what amendments are proposed, and what, if any, amendments are finalized.” EPA also states that “no research has been identified that is outside the scope of EPA’s current rule, but that would be within the scope of these proposed amendments.”

According to the proposed rule, the proposed amendments would change the 2006 rule in the following substantive respects:

  • By broadening the applicability of 40 C.F.R. Part 26, Subparts K, L, M, and Q, so these subparts would apply not only to research submitted to or considered by EPA under the pesticide laws, but also to research involving a “pesticide” (as defined by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)) which is submitted to or considered by EPA under any other regulatory statute it administers;
  • By incorporating the definition of “pesticide” from FIFRA, as a substance or mixture of substances intended for pesticidal effect;
  • By deleting from 40 C.F.R. Part 26, Subpart K, all references to consent on behalf of a subject in research involving intentional exposure to a pesticide by a subject’s “legally authorized representative”; and
  • By incorporating into 40 C.F.R. Part 26, Subparts P and Q, factors to be considered by EPA and the Human Studies Review Board (HSRB) in their review of proposed and completed research, derived from the recommendations of NAS in its 2004 Report to EPA, and from the Nuremberg Code.

The proposed amendments would make no changes to the Common Rule, which governs research with human subjects conducted or supported by EPA and many other federal departments and agencies. EPA’s codification of the Common Rule appears as Subpart A in 40 C.F.R. Part 26. The proposed amendments would also make no changes to Subparts B, C, and D of 40 C.F.R. Part 26. These subparts categorically prohibit any EPA research involving intentional exposure to any substance of human subjects who are children or pregnant or nursing women, and provide extra protections for pregnant women and for children who are the subjects of observational research conducted or supported by EPA.

EPA states that the proposed amendments would retain without substantive change the core provisions of the 2006 rule applying to the conduct of human pesticide research by third parties — i.e., research neither conducted nor supported by EPA or another Common Rule federal department or agency. These substantively unchanged provisions:

  • Categorically prohibit new research involving intentional exposure of pregnant or nursing women or of children to a pesticide;
  • Apply the provisions of the Common Rule to third-party human research involving intentional exposure of non-pregnant, non-nursing adults to a pesticide;
  • Require submission to EPA of proposals for new covered research before it is initiated;
  • Require persons who submit to EPA reports of completed human research on pesticides to document the ethical conduct of that research; and
  • Establish an independent HSRB to review and advise EPA concerning both proposals for new human research involving intentional exposure to a pesticide and reports of completed research on which EPA proposes to rely in its actions.

The proposed amendments would make only minor editorial revisions to 40 C.F.R. Part 26, Subpart O, which defines administrative actions available to EPA to address non-compliance with 40 C.F.R. Part 26, Subparts A through L. The proposed amendments would retain the essential structure of 40 C.F.R. Part 26, Subpart P, which defines the processes of EPA and HSRB review of proposed and completed research. The amendments, however, would also add substantial new clarifying language to 40 C.F.R. Part 26, Subpart P.

The proposed amendments would retain the essential structure of 40 C.F.R. Part 26, Subpart Q, which defines the standards to be applied when EPA proposes to rely on data from completed research involving intentional exposure of human subjects to a pesticide. The amendments, however, would also add substantial new clarifying language to 40 C.F.R. Part 26, Subpart Q.

The proposed amendments would not change the provision in 40 C.F.R. Part 26, Subpart Q, forbidding EPA to rely on any otherwise unacceptable research involving intentional exposure of human subjects to a pesticide, except under extremely restrictive conditions. These conditions require a public review by HSRB, an opportunity for public comment, and a showing by EPA that to do so would result in a more protective regulatory standard than could be justified without reliance on the unethical research.


In the proposed rule, EPA seems to wish to reassure NRDC and others who challenged the rule that the proposed changes would explicitly impose more certain restrictions against using pesticide research involving human subjects under any EPA regulatory program, while stressing that the proposed changes do not represent a significant increase in the expected burden of the rule. EPA goes to some length to describe the current rule and its implementation in somewhat self-congratulatory terms while imposing new, more explicit restrictions. For example, the text points out that EPA has concluded that no new (post-Food Quality Protection Act) research it has evaluated and found acceptable until now would be prohibited by the proposed changes, but the changes are being made nevertheless.

Similarly, EPA describes what is perhaps the most significant enhancement, extending the prohibition of using “pesticide” human subject research to data that support any EPA regulatory decision, in terms of how it will not greatly affect the other EPA programs. The text here describes how research to support a maximum contaminant level under the Safe Drinking Water Act, or air pollution research on sulfur dioxide under the Clean Air Act, will likely be unaffected even though the chemical in question may be part of a pesticide formulation. The key, however, is not those examples that can be readily contemplated and explained today, but the unforeseen consequences of cases where insufficient thought was given to some future “what if” given the broad requirements now proposed to apply to regulatory programs across EPA’s large universe.

Lastly, one interesting note is how EPA describes the very low number of proposals submitted under the current review procedures. It cites that actual practice over the past five years has seen only about 26 study proposals submitted for new (post-2006) research — about five per year instead of the predicted 33 per year. This is described in terms of showing the regimen’s minimal impact on the regulated community, while not asking whether the low number of study proposals indicates a set of obstacles that few applicants are willing or able to attempt to overcome.