Mitigation of quality and compliance risks in radio-pharmaceutical production by implementation of an automated release testing technology.

通过实施自动释放测试技术来减轻放射性药物生产中的质量和合规风险。

• 批准号: 9102704
• 负责人: Arkadij Elizarov
• 金额: $ 180万
• 依托单位: TRACE-ABILITY, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9102704
• 关键词: Mitigation; quality; compliance; risks; radio

Project Summary/Abstract Background. In the final 2009 PET drug cGMP rule (21 CFR Part 212) the FDA established safety standards and quality requirements for PET drug manufacturing. The inspections that followed between 2012 and 2015 have revealed unsolved issues unique to PET drug production. Problem. Due to their inherent short half-life (10-110 min) multiple PET drug batches are typically produced at multiple sites on a daily basis. The most labor-, skill- and risk-intensive part of the production process is release testing or quality control (QC) done on each batch. The most common PET drug, 18F- fluorodeoxyglucose (FDG), requires assessment of 10 different parameters before production is completed. Current procedures involve 18 manual operations, 8 visual assessments, 6 devices and 8 aliquots of FDG (Figure 1a). This reliance on manual operation, subjectivity and untraceable records presents a barrier to progress in PET drug manufacturing, limits the number of PET drugs that may be produced per day per facility, exposes the personnel to radiation risks and jeopardizes product quality and Part 212 compliance. Solution. Trace-Ability has pioneered the unique concept (Figure 1b) of assessing all QC parameters with a single mode of detection enabled by a micro-plate-based kit on a plate reader. The kit has reagents and features designed to yield optical signals that correlate with each parameter of PET tracer QC. It enables completely objective and traceable release testing from a single aliquot of the PET drug without any user interaction. Implementation of Tracer-QC is expected to achieve the following metrics for PET Drug manufacturers: (1) 25% reduction in (potential) 483’s; (2) Elimination of 75% of the quality risks identified during initial audit; (3) 50% reduction of QC technician’s radiation dose; (4) 20% operating cost reduction; (5) 50% reduction of time spent on QC-related activities; (6) 75% SOP reduction. The goal is to position Tracer-QC to deliver the metrics to the entire PET drug production industry. The technology’s novelty and limited regulatory exposure call for collaboration with the FDA to advance regulatory science to enable streamlined Tracer-QC implementation. Specific Aim 1: Using Tracer-QC prototypes, quantify along the metrics the improvement in production of FDG at 2 production facilities. Specific Aim 2: Validate optimized Tracer-QC solution in a way the FDA finds appropriate for industry- wide application. Specific Aim 3: Establish kit production that can support industry-wide adoption. Expected outcomes: (1) Improved quality of PET drugs and efficiency of release testing; (2) Modernization of PET drug production body of knowledge making it more robust, predictable and cost- effective; (3) Enhanced process control and reliable real time release; (3) 21 CFR Part 212: Ease of compliance by radiopharmaceutical manufacturers (4) Simplified oversight of PET drug production by the FDA; (5) Science-based quality standard; (6) Operator safety. Figure 1. (a) Current PET drug release testing and (b) Tracer-QC.

项目摘要/摘要 背景。在2009年的最终PET药物CGMP规则（21 CFR第212部分）中，FDA建立了安全性 宠物药物制造的标准和质量要求。随后进行的检查 2012年和2015年揭示了宠物药物生产独有的未解决问题。 问题。由于其继承了短期寿命（10-110分钟），多个PET药物批次通常为 每天在多个站点生产。生产中最劳动，技能和风险密集的部分 过程是在每批上进行的释放测试或质量控制（QC）。最常见的宠物药物，18f- 氟脱氧葡萄糖（FDG）需要在生产完成之前对10个不同参数进行评估。 当前程序涉及18次手动操作，8次视觉评估，6个设备和8个等分试样 （图1A）。手动操作，主观性和不可追踪记录的这种缓解呈现出障碍 宠物药物制造的进展，限制了每天可能生产的宠物药物的数量 设施，使该人面临辐射风险，并危害产品质量和第212部分的合规性。 解决方案。痕量能力启用了评估所有QC的独特概念（图1B） 具有单个检测模式的参数由板读取器上的基于微板的套件启用。套件 具有旨在产生与宠物示踪剂的每个参数相关的光学信号的试剂和功能 QC。它可以从宠物药物的单个等分试样进行完全客观和可追溯的释放测试 没有任何用户互动。预计实施Tracer-QC将实现以下指标 对于宠物药物制造商：（1）（潜在）483降低25％； （2）消除75％的质量 初始审核期间确定的风险； （3）QC技术人员的辐射剂量减少了50％； （4）20％运营 降低成本； （5）在QC相关活动上花费的时间减少了50％； （6）75％SOP减少。 目的是将Tracer-QC定位为将指标运送到整个宠物药物生产行业。 该技术的新颖性和有限的监管风险呼吁与FDA合作以促进 监管科学以实现简化的示踪QC实施。特定目标1：使用示踪剂QC 原型，沿指标量化了2个生产设施中FDG生产的改善。 特定目的2：以FDA认为适合行业的方式验证优化的示踪QC解决方案 广泛的应用。特定目标3：建立可以支持整个行业采用的工具包生产。 预期结果：（1）提高宠物药物的质量和释放测试效率； （2） 宠物药物生产知识体的现代化使其更加稳健，可预测和成本 - 有效的; （3）增强的过程控制和可靠的实时释放； （3）21 CFR第212部分：易于 放射药制造商的遵守（4）简化了对PET药物生产的监督 fda; （5）基于科学的质量标准； （6）操作员安全。 图1。（a）当前的PET药物释放测试和（b）Tracer-QC。