In a potential sign of renewed interest in financial ties between industry and clinical investigators, the Food and Drug Administration’s (FDA) Office of New Drugs (OND) recently issued a new Manual of Policies and Procedures (MAPP) outlining the Office’s policy goals, roles, and responsibilities with respect to financial disclosures in NDAs, BLAs and NDA/BLA supplements. These financial disclosures have been required under 21 CFR Part 54 since the final rule became effective in 1999.
Under 21 CFR Part 54, a sponsor of an NDA, BLA, or NDA/BLA supplement must disclose, for covered clinical studies, specified financial interests that clinical investigators have in the sponsoring company or in the product under development. Alternatively, the sponsor must certify to the absence of such financial interests. The purpose of these disclosures is to enable the agency to assess whether clinical investigators’ financial interests may have affected the reliability of clinical data included in an application. It has been relatively unclear, however, to what extent and how FDA has taken these financial disclosures into account when evaluating an application.
New MAPP 6021.1, which OND issued on June 21, 2017, establishes specific policies and procedures for FDA staff to follow to assess financial disclosure information. For example, the MAPP states that if a sponsor informs the agency of relevant financial interests during the development process, those interests will be agenda items for discussion at key meetings (e.g., end-of-phase 2, pre-IND, pre-NDA) with the sponsor. The MAPP also states that the agency can refuse to file an application if it does not include the required certifications or disclosures; at the same time, inadequate financial disclosures will not serve as the sole basis for a refuse-to-file or complete response action unless the OND Immediate Office is first consulted.
Significantly, the MAPP notes that the adequacy of the financial disclosures will be determined during an application’s medical review, and that the medical reviewer will notify the Office of Science Investigations (OSI) if it appears that financial arrangements may have impacted the reliability of the data. In a situation where questionable study results are associated with a clinical investigator for whom financial interests were disclosed, the MAPP instructs the medical reviewer to (a) consult OSI about a possible visit to the clinical site, and (b) request submission of further analyses of the data (e.g., an analysis of the study omitting the investigator’s data).
Finally, the MAPP instructs the medical reviewer to make a recommendation to the review division on whether the specific data can be considered when taking regulatory action on the application, and to summarize in the Medical Review the findings of the financial disclosure review and any steps taken as a result of the financial disclosures.
It remains to be seen what the implications of this MAPP may be, but its issuance, together with the issuance in 2013 of a guidance regarding financial disclosure by clinical investigators, may signal that the agency is planning to focus more systematically and closely on assessing potential bias in clinical data based on clinical investigators’ financial interests. If you have any questions about the new MAPP or FDA’s financial interest disclosure requirements more generally, please contact one of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.