Developing Nanodosing of Iobenguane I 131 for Radiotherapy

描述（由申请方提供）：本II期SBIR用于开发在I期SBIR奖项（R43 CA 15120 -01）中鉴定和证明的制剂。最终目标是生产、销售和输送高比活度碘苯胍I 131，用于患有神经内分泌肿瘤的成人和儿童的放射治疗。这些是罕见的肿瘤，在美国每年只有大约800例，但结果很差，没有批准的有效治疗方法。该提案的创新之处在于，它使用固相合成方法来制备放射治疗量（1居里）的经证实的诊断剂，而不需要放射活性载体化合物。FDA进行了B型IND前开发，他们明确指出USP检测方法不足以允许对通过新方法生产的碘苯胍I 131进行人体检测。然而，FDA的结论是，文献报告表明碘苯胍I 131疗法可有效治疗神经内分泌肿瘤，并授予孤儿药和快速治疗地位，用于开发高比活性制剂。为了满足IND申请的化学、生产和控制组件的组件的所需质量控制，将根据当前良好生产规范和开发并验证的分析检测来生产聚合物支持的药物前体，以确认关键组分药物前体的同一性、纯度、性能和杂质谱。我们还将制定药物主文件，并执行放射性原料药生产工艺的批记录。最后，将制备最终制剂批次，并在转运蛋白表达细胞和动物中检测稳定性和生物等效性。

DESCRIPTION (provided by applicant): This Phase 2 SBIR is for the development of a drug product identified and demonstrated in the Phase 1 SBIR award (R43CA15120-01). The ultimate goal is to produce, sell and deliver doses of high specific activity iobenguane I 131 for radiotherapy in adults and children with neuroendocrine tumors. These are rare tumors with only about 800 cases a year in the US but with poor outcome and no approved effective treatment. The innovation in this proposal is that it uses a solid phase synthetic process to make a proven diagnostic agent in a radio-therapeutic quantity (1 Curie) without the pharmacologically active carrier compound. A type B pre-IND development was held with the FDA where they definitively stated that USP test methods are insufficient to permit human testing of iobenguane I 131 produced by a new method. However, the FDA concluded that literature reports indicate iobenguane I 131 therapy is efficient for treating neuroendocrine tumors and granted Orphan Drug and Fast Tract status for the development of high specific activity drug product. To meet the required quality control of components of the chemistry, manufacturing and controls component of a IND application, the polymer supported drug precursor will be produced according to current good manufacturing practices and analytical tests developed and validated to confirm the identity, purity, performance and impurity profile of the critical component drug precursor. We will also develop a Drug Master File and execute batch records for the production process of the radioactive drug substance. Finally batches of the final drug product will be made and tested for stability and bio-equivalence in transporter expressing cells and in animals.