Scholarlink

Purpose <p>NUT carcinoma is an ultra-rare and highly aggressive malignancy lacking authorised systemic therapies. Birabresib, a bromodomain and extra-terminal (BET) inhibitor, has shown preliminary clinical activity; however, its development was discontinued and no GMP-grade active pharmaceutical ingredient or finished product is available. This work describes the hospital-based pharmaceutical development enabling authorised therapeutic use of birabresib in France.</p> Methods <p>Within the French ANSM temporary usage protocol (PUT), a quality- and risk-based Chemistry, Manufacturing and Controls (CMC) strategy inspired by ICH Q8–Q10 was implemented to convert a research-grade material into a qualified drug substance for compounding. An initial batch of birabresib dihydrate underwent comprehensive CMC-like characterisation, including purity, identity, structural confirmation, solid-state properties, residual solvents, and forced degradation to establish a primary chemical reference substance and a stability-indicating analytical method.</p> Results <p>The generated data supported acceptance criteria for subsequent batches and for 20-mg capsules compounded under Good Preparation Practice in a centralised hospital pharmacy. Finished product controls complied with pharmacopoeial and ICH requirements, and capsules were enrolled in a prospective stability programme under PUT-defined storage conditions.</p> Conclusions <p>This risk-proportionate, CMC-oriented hospital framework enabled the first authorised therapeutic use of birabresib in NUT carcinoma and may be extended to other discontinued small molecules used in regulated access programmes for ultra-rare diseases.</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

Hospital-Compounded Birabresib Capsules for NUT Carcinoma: A Quality- and Risk-Based CMC Strategy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

查看全文
  • Maxime Annereau,
  • François-Xavier Legrand,
  • Maria Virginia Sánchez-Becerra,
  • Stéphanie Ramos,
  • Françoise Duperray,
  • Lucas Denis,
  • Christina Sizun,
  • Sylvère Durand,
  • Valérie Salomon,
  • Benjamin Besse,
  • Bernard Do

摘要

Purpose

NUT carcinoma is an ultra-rare and highly aggressive malignancy lacking authorised systemic therapies. Birabresib, a bromodomain and extra-terminal (BET) inhibitor, has shown preliminary clinical activity; however, its development was discontinued and no GMP-grade active pharmaceutical ingredient or finished product is available. This work describes the hospital-based pharmaceutical development enabling authorised therapeutic use of birabresib in France.

Methods

Within the French ANSM temporary usage protocol (PUT), a quality- and risk-based Chemistry, Manufacturing and Controls (CMC) strategy inspired by ICH Q8–Q10 was implemented to convert a research-grade material into a qualified drug substance for compounding. An initial batch of birabresib dihydrate underwent comprehensive CMC-like characterisation, including purity, identity, structural confirmation, solid-state properties, residual solvents, and forced degradation to establish a primary chemical reference substance and a stability-indicating analytical method.

Results

The generated data supported acceptance criteria for subsequent batches and for 20-mg capsules compounded under Good Preparation Practice in a centralised hospital pharmacy. Finished product controls complied with pharmacopoeial and ICH requirements, and capsules were enrolled in a prospective stability programme under PUT-defined storage conditions.

Conclusions

This risk-proportionate, CMC-oriented hospital framework enabled the first authorised therapeutic use of birabresib in NUT carcinoma and may be extended to other discontinued small molecules used in regulated access programmes for ultra-rare diseases.