House committee report signals limits on foreign clinical data

The report signals the Committee's interest in a significant departure from FDA's current regulatory framework, which permits reliance on foreign clinical data in support of INDs, subject to good clinical practice and FDA's ability to validate the data. By purporting to exclude data from the four covered nations at the IND stage, the Committee's position would cabin FDA's discretion and could require significant restructuring of development programs that rely on clinical trial data generated in those covered nations.

Importantly, the restrictive language appears in the Committee report accompanying the bill, rather than in the bill text itself. As a result, this restriction would not carry the force of law even if Congress enacted the bill as currently drafted (which we currently think is unlikely). The provision is a strong policy signal, however, and is consistent with recent U.S. biosecurity legislative initiatives affecting the life sciences sector. 

The report language

The report reflects the Committee's desire to “prohibit[] FDA from accepting, reviewing, or considering any covered clinical data generated by a clinical investigation site located in a covered nation as defined in 10 U.S.C. 4872(f) in support of an investigational new drug application under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) or section 351 of the Public Health Service Act (42 U.S.C. 262), including any amendment or supplement thereto.” 

Notably, the report does not acknowledge that FDA's existing IND regulations actually require the submission of a “brief summary of previous human experience with the drug . . . [and] investigational or marketing experience in other countries that may be relevant to the safety of the proposed clinical investigation(s).” 21 CFR 312.23(a)(3)(ii).

Moreover, the report language does not address the submission of clinical data from covered nations to New Drug Applications (NDAs) or Biologics License Applications (BLAs). As with the IND regulations, FDA's NDA regulations require the submission of a description of and analysis of all previous studies of the drug, regardless of where they were conducted.

Key features of the report language include:

• Covered nations: China, Russia, North Korea, and Iran, as defined by 10 U.S.C. 4872(f).
• Scope: All IND applications, amendments, and supplements submitted under 21 U.S.C. 355 (drugs) and 42 U.S.C. 262 (biologics).
• Effective date: One year after enactment, to allow FDA time to issue implementing guidance and sponsors time to adjust their development strategies.
• Rationale: The Committee explained that China-based sites operate outside of FDA inspection authority, in jurisdictions where patient safety standards, human rights, and independence from state interference cannot be verified. Trials can be conducted three to five times faster in China, which the Committee believes incentivizes companies to conduct their trials there, and in turn creates a risk of transferring scientific know-how to a foreign adversary. Presumably, the Committee holds these same concerns with respect to Iran, North Korea, and Russia.

The current state of IND applications and foreign clinical data

Under existing FDA regulations at 21 CFR 312.120, sponsors may rely on foreign clinical studies not conducted under an IND to support IND applications provided that, among other things, the studies are conducted in accordance with good clinical practice and FDA can validate the data through an onsite inspection. In other words, the current framework affords FDA discretion to assess the quality and applicability of foreign data. The Committee's position would remove FDA discretion to accept IND-enabling data generated at covered-nation sites.

Considerations for pharmaceutical and biotech companies and investors

The fate of both the Committee report language and the underlying bill remains highly uncertain. The appropriations process is lengthy and unpredictable, and report directives of this nature do not always survive intact through the full legislative cycle, much less make their way into enacted law. That said, agencies often take cues from their appropriators even if those directives are never enacted into law, and the Committee's expressed preference on this issue could foreshadow measures to apply more scrutiny to data from covered nations.

Companies with development programs that include or contemplate sites in covered nations might consider the following prudent risk management measures given the broader legislative trend at both the federal and state levels toward restricting foreign adversary access to biological data and research.

• Advancing China-based assets. Sponsors planning to rely solely on clinical studies sited in China to support U.S. drug candidates could face real urgency to advance those assets into IND-enabling stages in China, and to file INDs, should a restriction ultimately take effect. Companies should start evaluating whether acceleration of IND-enabling studies in covered nations is feasible for any of their existing assets.
• Existing INDs with planned amendments and supplements. Sponsors holding active INDs that plan to incorporate covered-nation data in future amendments or supplements should assess their exposure, as any potential restriction like the report language could extend to not only new INDs but to all amendments and supplements.
• Risk of FDA reevaluating previous IND decisions. Even for INDs that are already in effect, FDA may reevaluate the underlying China-based clinical data at any time with a heightened scrutiny to reflect the changing regulatory landscape. Sponsors of such INDs might consider supplementing them with additional clinical data from other countries in order to mitigate any risk that such IND is placed on a partial or full clinical hold.
• Development program restructuring. Sponsors that currently rely on China-based clinical trials to generate clinical data to support IND submissions might consider restructuring development strategies and potentially exploring early-stage clinical trials in other regions, such as the EU or Australia.
• Transaction due diligence. Companies actively evaluating acquisition or in-licensing of China-originated assets should factor potential IND data restrictions into deal diligence and valuation. An asset supported solely by China-based clinical trial data may face a more complex, time consuming, and costly regulatory path to U.S. market than anticipated.

We will continue to monitor this report language and related developments through the appropriations process. In the meantime, please reach out to the authors of this alert or the Hogan Lovells attorneys with whom you usually work with questions about your development program.

Authored by Xin Tao, Robert Church, Elizabeth Jungman, Heidi Gertner, Cybil Roehrenbeck, and Eman Al-Hassan