Scholarlink

<p>The U.S. Food and Drug Administration (FDA) issues Complete Response Letters (CRLs) when drug approval applications are deemed inadequate. Despite their scientific, regulatory, and commercial significance, little systematic evidence exists regarding deficiencies cited in these letters. We conducted a cross-sectional analysis of publicly available CRLs for new molecular entities ultimately approved by the FDA between 2020 and 2024. We assessed deficiencies in efficacy, safety, pharmacokinetics/pharmacodynamics (PK/PD), manufacturing facilities, Chemistry, Manufacturing and Controls (CMC), and labeling, as well as proposed remedies. Among 43 novel therapeutics with CRLs, manufacturing deficiencies were most common (65% facilities; 51% CMC), followed by labeling (44%), efficacy (26%), safety (26%), and PK/PD concerns (14%). Most letters cited multiple issues, with moderate correlation between efficacy and safety deficiencies (r = 0.51, <i>p</i> &lt; 0.001). The FDA most frequently recommended updated safety analyses (98%), facility remediation (65%), additional CMC submissions (51%), and labeling revisions (42%), while new clinical trials were requested in 26% of cases. Less common remedies included PK/PD data, statistical reanalyses, and nonclinical studies. Median times from CRL receipt to resubmission and approval were 0.60&#xa0;years (0.40–1.42) and 1.28&#xa0;years (0.87–1.81), respectively. These findings highlight wide-ranging obstacles to drug approval and suggest greater transparency could improve public understanding and regulatory accountability.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Deficiencies Delaying Prescription Drug Approvals by the U.S. Food and Drug Administration, 2020–2024

  • 期刊论文

  • 发表日期：

    2026年2月11日

查看全文
  • Sophie Dilek,
  • Richard H. Woods,
  • Jeromie Ballreich,
  • Thomas J. Moore,
  • G. Caleb Alexander

摘要

The U.S. Food and Drug Administration (FDA) issues Complete Response Letters (CRLs) when drug approval applications are deemed inadequate. Despite their scientific, regulatory, and commercial significance, little systematic evidence exists regarding deficiencies cited in these letters. We conducted a cross-sectional analysis of publicly available CRLs for new molecular entities ultimately approved by the FDA between 2020 and 2024. We assessed deficiencies in efficacy, safety, pharmacokinetics/pharmacodynamics (PK/PD), manufacturing facilities, Chemistry, Manufacturing and Controls (CMC), and labeling, as well as proposed remedies. Among 43 novel therapeutics with CRLs, manufacturing deficiencies were most common (65% facilities; 51% CMC), followed by labeling (44%), efficacy (26%), safety (26%), and PK/PD concerns (14%). Most letters cited multiple issues, with moderate correlation between efficacy and safety deficiencies (r = 0.51, p < 0.001). The FDA most frequently recommended updated safety analyses (98%), facility remediation (65%), additional CMC submissions (51%), and labeling revisions (42%), while new clinical trials were requested in 26% of cases. Less common remedies included PK/PD data, statistical reanalyses, and nonclinical studies. Median times from CRL receipt to resubmission and approval were 0.60 years (0.40–1.42) and 1.28 years (0.87–1.81), respectively. These findings highlight wide-ranging obstacles to drug approval and suggest greater transparency could improve public understanding and regulatory accountability.