Pharma Forum Dialogues

FDA Releases Draft Guidance on New Risk Information for Approved Drugs

Posted by New York Pharma Forum Inc. on Jul 16, 2014 5:07:00 PM

By Al Cacozza and Sarah Blankstein, Ropes & Gray

On June 6, 2014, the Food and Drug Administration (“FDA”) issued a draft guidance on new risk information for approved drugs. The document is entitled “Guidance for Industry: Distributing Scientific and Medical Publications on Risk Information for Approved Prescription Drugs and Biological Products—Recommended Practices.”  This post summarizes the key aspects of that document.

risk information for new drugs

Scope of the Draft Guidance on New Risk Information

The draft guidance creates a very narrow safe harbor under which a manufacturer of a prescription drug or biological product (‘product”) may distribute risk information that may be inconsistent with the risk information contained in the product’s approved labeling.  The underlying assumption is that FDA has acknowledged it is not necessarily false or misleading to disseminate information that does not meet the “substantial evidence” standard established in the agency’s regulations. 

The safe harbor applies to the distribution to health care professionals (“HCPs”) of peer-reviewed publications containing “new risk information” about approved products.  That term is defined as “information that becomes available after a drug is marketed that rebuts or mitigates information about a risk already identified in the approved labeling or otherwise refines risk information in the approved labeling in a way that does not indicate greater seriousness of the risk.”  The draft guidance expressly excludes information about a newly identified risk or new information that indicates a risk identified in approved labeling is more serious than reflected in the labeling from the definition of “new risk information.” 

risk information for approved drugs and biologics
Al Cacozza, Partner, Ropes & Gray LLP

Distribution Principles for New Risk Information

The draft guidance recognizes that there are limits on the ability of premarket risk assessment to fully characterize a drug’s safety profile and that it is important to provide a mechanism for distributing useful new risk information to HCPs in a timely manner.  FDA, therefore, “does not intend to object” to distribution of medical and scientific publications containing new risk information that “rebuts, mitigates, or refines risk information in the approved labeling” if the following criteria are satisfied:

Data Source:

The study or analysis should meet accepted design and other methodologic standards and be “sufficiently well-designed and informative to merit consideration” of the risk discussed.

  • The study or analysis should be “at least as persuasive as” the data that underlie the existing risk assessment of causality, severity, and/or incidence of the adverse reaction as reflected in approved labeling.
  • The conclusions should give “appropriate weight and consideration to, and should be a fair characterization of, all relevant information in the safety database,” including contrary or otherwise inconsistent findings.
  • The study or analysis should be published in an independent, peer-reviewed journal.


  • The reprint should be accompanied by a cover sheet that “clearly and prominently” discloses: (1) the study design, critical findings, and significant limitations that may limit the persuasiveness or scope of findings; (2) that the information is not consistent with certain risk information in the approved labeling; (3) that FDA has not reviewed the data; and (4) any financial interests or affiliations between the study authors and the firm.
  • The reprint should be accompanied by the approved labeling.
  • The reprint should be distributed separately from any promotional material.
  • Any statements made by a representative of the firm to a recipient concerning the reprint should be consistent with its content and the information in the disclosure cover sheet. 

risk information for approved drugs and biologics

Sarah Blankstein, Associate, Ropes & Gray LLP 

Practical Considerations

The draft guidance contemplates that a single new controlled trial, an epidemiologic study, or a rigorous meta-analysis could qualify for distribution to HCPs.  This concession is significant, because those types of evidence would not normally satisfy the “substantial evidence” standard established by FDA’s regulationsgenerally two adequate and well-controlled clinical studies.

Nevertheless, firms may find it difficult in practice to satisfy the safe harbor requirements created by the draft guidance.  For example, the requirement that the publication be “at least as persuasive as the data sources that underlie the existing risk assessment” being rebutted, mitigated, or refined is ambiguous. In addition, while the draft guidance limits distribution only to those studies that are a “fair characterization of all relevant information in the safety database,” it is unlikely that many peer-reviewed articles are written in a way to satisfy that requirement. 

The draft guidance states that the reprints must be distributed separately from any promotional materials, and FDA implies the reprint itself does not qualify as promotional material.  The draft guidance indicates that “a representative of the firm,” presumably including a sales representative, may make statements concerning the reprint to the HCP as long as the statements are consistent with the reprint.   

It remains to be seen whether any regulatory changes made by FDA will result in additional flexibility or additional scrutiny over manufacturer communications regarding truthful, non-misleading information for approved or cleared products. 

Al Cacozza is a partner in Ropes & Gray’s life sciences group and provides advice to a variety of life sciences and health care clients on legislative, regulatory and corporate matters. The focus of Al’s practice is FDA regulation of pharmaceuticals, biologicals and over-the-counter (OTC) drugs, with special emphasis on issues related to advertising and promotion. He also counsels his life sciences clients on compliance with health care fraud and abuse laws and health information privacy laws. Al provides legal and strategic advice on competitive issues related to product life cycle management. In recent years, Al has taken a lead role in numerous internal and government compliance investigations.

Sarah Blankstein, an associate at Ropes & Gray, joined the firm's corporate department in 2013. During law school, Sarah interned at the U.S. Attorney’s Office in Washington, D.C. She also participated in the Health Law and Policy Clinic, working on a range of state and federal policy initiatives designed to increase access to quality health care. Prior to attending law school, Sarah spent two years as a researcher in a genetics lab at the University of Miami. 

Ropes & Gray is an associate member of New York Pharma Forum.

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Topics: FDA guidance