Want an investigation into data irregularities? Don’t use the Citizen Petition process, FDA says

In a response last week to a law firm seeking a clinical hold and an investigation into alleged data irregularities, the FDA said regardless of the merits of the complaint, it was unable to respond based on commercial confidentiality and regulatory concerns. While FDA’s response is likely welcome news for companies hoping to avoid an increase in similar petitions during the development process, the FDA did not provide any preferred alternative methods of raising data integrity concerns.

Regulatory Background

• A Citizen Petition is a formal petition made to the FDA by a person or organization requesting that the FDA take a particular action. Under 21 CFR 10.30, the petition may request that the FDA “issue, amend, or revoke” a regulation, an order, or “refrain for taking any other form of administrative action.” Often, these petitions are used to request that the agency amend regulations or that the FDA refrain from approving a specific generic drug without first subjecting it to specific testing criteria.
• Upon receipt of a Citizen Petition, the FDA then has either 90 or 150 days (depending on the petition type) in which to review the petition and take action. There are several different types of actions the FDA may take with respect to a petition, from approval (i.e., take the requested action), denial, partial denial (i.e., take some but not all of the requested actions), dismissal (i.e., the petition is moot due to other changes made by the FDA or Congress), or provide a tentative response (most often a delay).
• The type of action taken often depends on what is being requested of the FDA. Citizen Petitions seeking FDA’s permission to develop a different dose of an existing drug (known as a Suitability Petition) are often granted. Petitions seeking regulatory changes are sometimes granted, though often after lengthy delays following an interim response. And petitions seeking to “delay or deny” the approval of another drug – also known as 505(q) petitions – are most often rejected.
• While the FDA often rejects petitions it believes to be without merit, some petitions may still serve to delay the approval of some drugs – and in particular, generic drugs. The FDA is legally required to respond to 505(q) petitions within 150 days of their submission, although it may (and often does) extend the review period if the agency needs more time. Because the issues raised are often complex, the agency typically expends significant resources in analyzing those issues and responding to them.

Regulatory Context

• In August 2021, the FDA received a somewhat unusual Citizen Petition from the law firm Labaton Sucharow, which made serious allegations against Cassava Sciences.In the petition, Sucharow partner Jordan Thomas requested that the FDA place a clinical hold on two pivotal clinical trials being run by Cassava investigating its Alzheimer’s disease drug, Simufilam. The petition claimed “grave concerns about the quality and integrity of the laboratory-based studies surrounding this drug candidate and supporting the claims for its efficacy.”
• In short: The petition requested the FDA halt the studies to allow for a “thorough audit of the publications and data relied on by Cassava in support of its claims.” The petition identified four areas of concern with the underlying supporting data: A “series of anomalies that are suggestive of systemic data manipulation and misrepresentation”; study methodologies that were illogical; re-testing of clinical biomarker data resulting in more favorable outcomes; and aspects of research “incompatible with scientific norms.”
• Based on those concerns, Thomas requested that the FDA pause “the ongoing clinical trials until the FDA can conduct and complete a rigorous audit of Cassava’s research.” The law firm subsequently amended its petition with additional exhibits and information to further support its case. In one such filing, the law firm claimed the FDA had a “duty to immediately halt the simufilam clinical trials, conduct a rigorous audit of all the company’s research and clinical trial results, and report the agency’s finding to interested law enforcement and regulatory authorities.”

The FDA’s new response to the petition that likely has wider implications for the life sciences industry.

• Late last week the FDA rejected the petition, but on procedural grounds – not on its merits. FDA’s argument in its response is noteworthy, stating that contrary to 21 CFR 10.30, which allows a person to request an administrative action, “an investigation is not an administrative action.” Further, since an investigation would “necessarily require fact finding beyond what is presented in the current administrative record,” a Citizen Petition is not the appropriate venue for such a request.
• But the FDA raised other procedural concerns as well, including the importance of maintaining commercial confidentiality. Responding to the petition, the FDA wrote, “would appear to require FDA to publicly disclose information about an investigational new drug that, by law, FDA generally cannot publicly disclose” under the Trade Secrets Act. As interpreted by the FDA, the law prevents the disclosure of “confidential commercial information,” including the existence of an application unless it “has previously been publicly disclosed or acknowledged.” Even if an application has previously been publicly disclosed, the FDA will still generally “not make any data or information contained in the application … available for public disclosure before the agency sends an approval letter.”
• Finally, the FDA also indicated that requests for law enforcement action are “similarly not amenable to the Citizen Petition process.” As explained by the agency in its response, “Requests for the Agency to initiate enforcement action and related regulatory activity are expressly excluded from the scope of FDA’s citizen petition procedures.” Regulators cited 21 CFR 10.30(k), which notes that it “does not apply to the referral of a matter to a U.S. attorney for the initiation of court enforcement action and related requests.”
• While the petition was firmly rejected, the FDA did extend an olive branch of sorts to Labaton Sucharow. “We take the issues you raise seriously,” wrote Patrizia Cavazzoni, the director of the Center for Drug Evaluation and Research – an unusually high-level of respondent for a routine petition response. “Please note that your Petitions are being denied solely on the grounds that your requests are not the appropriate subject of a citizen petition. This response does not represent a decision by the Agency to take or refrain from taking any action relating to the subject matter of your Petitions.”

What this petition means for the life sciences industry

• With this action, the FDA seems keen to avoid short-sellers, attorneys and others from pre-empting the review process. FDA’s insistence that this is both the wrong venue and that it’s unable to comment reduces the possibility that a wave of other Citizen Petitions will be filed, taking up valuable and scarce review resources.
• That’s likely good news for life sciences companies in general, who won’t have to worry (as much) about defending themselves against petitions that might serve to delay their approval decisions (such as by placing their products on a clinical hold).
• But it’s also clear that the FDA still wants to be made aware of data integrity issues, and that it may still take action on this request in other ways. Here, FDA’s response to the petition indicates that this is the wrong venue for such a request, even if the request itself may be merited. “Please note that your Petitions are being denied solely on the grounds that your requests are not the appropriate subject of a Citizen Petition,” it wrote.
• The key question, then, is what venue does the FDA want companies to make use of for such requests? For now, the agency isn’t saying. The response to the petition makes no mention of a preferred avenue for the request. That could result in some companies continuing to make use of the Citizen Petition process to elevate the public and regulatory attention their requests receive, even if they are unlikely to succeed. The FDA may wish to offer preferred alternatives if they hope to dissuade entities from making use of this pathway.

To contact the author of this analysis, please email Alexander Gaffney ( [email protected]).

Key Documents and Dates

• Citizen Petition Docket
• FDA Response