On July 23, the U.S. Food and Drug Administration (FDA) announced a new proposed rule that would require sponsors and manufacturers who provide an ‘‘eligible investigational drug’’ under the Right to Try Act to submit an annual summary of such use to FDA. The agency invites public comment on several aspects of the proposed rule, including who should be required to report, and whether this information should be submitted separately from annual IND reports.

“Right to Try” is one pathway for certain patients with life-threatening conditions to seek treatment with investigational drugs that are still in clinical trials or have a pending NDA or BLA, while bypassing FDA’s existing requirements for the Expanded Access program at 21 CFR 312 Subpart I, as well as other clinical trial regulations (e.g., Institutional Review Board approval). Additional background and analysis of the pathway is available online here.

Now, FDA has issued a new proposed rule that, if finalized, would implement the annual reporting requirements of the Right to Try Act. The proposed rule tracks closely to the act, requiring the sponsor or manufacturer of an investigational drug offered to patients under the Right to Try Act to submit an annual summary that reports, among other things, the disease or condition for which the drug was used. Interestingly, the COVID-19 pandemic has compelled the government to seek to track the results of the use of unapproved drugs for certain uses. Speaking at a press conference in March, FDA Commissioner Stephen Hahn touted the importance of the agency having as much data and information as possible to determine whether experimental treatments for COVID-19 are safe and effective.

Under the proposed rule, the Right to Try annual report would include:

1. the name of the eligible investigational drug and applicable IND number,
2. number of doses supplied,
3. number of patients treated,
4. use for which the eligible investigational drug was made available, and
5. any known serious adverse events and outcomes.

The proposed rule would also require that the reports be submitted by March 31 of each year, and would include data from Jan. 1 through Dec. 31 of the previous year. Following submission, FDA would make a consolidated version of the reports publicly available. The first annual reports submitted under this regulation would be required to include any Right to Try use of a drug from the time of enactment of the Right to Try Act (May 30, 2018), through the date the final rule becomes effective.

Notably, the Right to Try annual summary would be submitted separately from annual IND report required by 21 CFR 312.33, and FDA proposes to add the requirement in 21 CFR Part 300 rather than within the investigational new drug regulations of Part 312 as was contemplated by the Right to Try Act. FDA provided the following rationale in support of this approach:

“We concluded that a separate process will help to ensure that information about the use of eligible investigational drugs under the Right to Try Act is identified by FDA. We believe sponsors who provide drugs under the Right to Try Act will appreciate this effort to keep the information separate. This approach will also enhance FDA’s ability to quickly identify and compile this information so we can post the required annual summary of these reports.”

We believe this text illustrates FDA’s interest in maintaining clear separation between the traditional regulatory framework for investigational drugs under 21 CFR Part 312, and the new Right to Try pathway. FDA requests comments on whether separate reports would be overly burdensome.

FDA also invites comments on who should be considered a “manufacturer or sponsor,” and thus held responsible for submitting the annual reports to the agency. FDA proposes the definition as someone who initiates or takes responsibility for the clinical investigations and pending applications, or who produces the finished version of the investigational drug that’s provided. Notably, under the proposal, this would not include entities that produce only a component of the investigational drug, such as an inactive pharmaceutical ingredient included in the final drug product.

Interestingly, FDA’s current estimate is that only 6 sponsors and manufacturers will file an annual report, indicating their belief that the law is not being broadly utilized at this time. By contrast, CDER and CBER received 1,748 Expanded Access requests combined in FY 2016.[1]

There have been concerns raised about how FDA might assess the data generated from the new Right to Try program and whether that data can be used to support or inhibit new drug approvals. Accordingly, the Right to Try Act limits the circumstances in which FDA may use clinical outcome data derived from the program to delay or adversely affect the review and approval of drug products to situations in which the drug’s sponsors request the use, or in which FDA determines that the clinical outcome data is critical to determining the safety of the eligible investigational drug.

Comments on the proposed rule are due by September 22, 2020. 

[1] https://www.fda.gov/media/119971/download (data for the number of manufacturers participating in the Expanded Access program annually was not reported).