Pre-ANDA strategy and Human Factors activities to de-risk pharmaceutical companies ANDA submission of drug–device combination products: case study of a formative Comparative Use Human Factors study

This article presents a strategy that a Drug Delivery Device Developer (DDDD) has adopted to support Abbreviated New Drug Application (ANDA) submissions of drug–device combination products. As per the related FDA guidance, a threshold analysis should be compiled. If ‘other differences’ between the Reference Listed Drug (RLD) and the generic drug devices are identified, a Comparative Use Human Factors (CUHF) study may be requested. The DDDD performed task analysis and physical comparison to assess the pen injector design differences. Then, a formative CUHF study with 25 participants simulating injections using both RLD and the generic pen injectors was conducted. After each participant completed four simulated injections, similar type and rates of use error between the RLD (0.70) and generic (0.68) pen injectors were observed. DDDDs can support pharmaceutical companies in the ANDA submission strategy of their drug–device combination product by initiating comparative task analysis and physical comparison of the device as inputs for the threshold analysis. If ‘other differences’ are identified, a formative CUHF study can be performed. As shown in our case study, this approach can be leveraged to support the sample size calculation and non-inferiority margin determination for a CUHF study with the final combination product.

本文介绍了某给药装置开发商（Drug Delivery Device Developer, DDDD）为支持药械组合产品的简化新药申请（Abbreviated New Drug Application, ANDA）申报所采用的策略。根据美国食品药品监督管理局（Food and Drug Administration, FDA）相关指南要求，需编制阈值分析文件。若识别出参比制剂（Reference Listed Drug, RLD）与仿制药装置间存在“其他差异”，则可能被要求开展比较使用人为因素（Comparative Use Human Factors, CUHF）研究。该给药装置开发商通过开展任务分析与实物比对，评估笔式注射器的设计差异。随后，研究团队招募25名受试者开展形成性CUHF研究，要求受试者分别使用参比制剂配套笔式注射器与仿制药笔式注射器进行模拟注射操作。每名受试者完成4次模拟注射后，研究人员观察到参比制剂笔式注射器（使用错误率0.70）与仿制药笔式注射器（使用错误率0.68）的使用错误类型及发生率均较为相似。给药装置开发商可通过启动装置的对比任务分析与实物比对，将其作为阈值分析的输入依据，以此为制药企业的药械组合产品ANDA申报提供策略支持。若识别出“其他差异”，则可开展形成性CUHF研究。正如本案例研究所展示的，该方法可用于为最终药械组合产品的CUHF研究提供样本量计算与非劣效界值确定的支持。