Department of Chemistry, University of Puerto Rico, Mayaguez, United States; Janssen Ortho LLC-Gurabo, PR, United States.
Janssen Supply Chain, Johnson & Johnson, New Brunswick, NJ, United States.
Int J Pharm. 2018 Mar 1;538(1-2):167-178. doi: 10.1016/j.ijpharm.2018.01.003. Epub 2018 Jan 30.
The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial least squares (PLS) regression. The authors understand that this is the first study where the continuous manufacturing (CM) equipment was used as a gravimetric reference method for the calibration model. A principal component analysis (PCA) model was also developed to identify the powder blend, and determine whether it was similar to the calibration blends. An air diagnostic test was developed to assure that powder was present within the interface when the NIR spectra were obtained. The air diagnostic test as well the PCA and PLS calibration model were integrated into an industrial software platform that collects the real time NIR spectra and applies the calibration models. The PCA test successfully detected an equipment malfunction. Variographic analysis was also performed to estimate the sampling analytical errors that affect the results from the NIR spectroscopic method during commercial production. The system was used to monitor and control a 28 h continuous manufacturing run, where the average drug concentration determined by the NIR method was 101.17% of label claim with a standard deviation of 2.17%, based on 12,633 spectra collected. The average drug concentration for the tablets produced from these blends was 100.86% of label claim with a standard deviation of 0.4%, for 500 tablets analyzed by Fourier Transform Near Infrared (FT-NIR) transmission spectroscopy. The excellent agreement between the mean drug concentration values in the blends and tablets produced provides further evidence of the suitability of the validation strategy that was followed.
描述了在经过 FDA 批准的商业生产现场实施过程分析技术和连续制造的情况。在这个直接压片工艺中，使用偏最小二乘（PLS）回归法开发的近红外（NIR）光谱校准模型来监测所生产的混合物。作者认为，这是首次使用连续制造（CM）设备作为校准模型的重量参考方法的研究。还开发了主成分分析（PCA）模型来识别粉末混合物，并确定其是否与校准混合物相似。开发了空气诊断测试，以确保在获得 NIR 光谱时接口内有粉末。空气诊断测试以及 PCA 和 PLS 校准模型已集成到一个工业软件平台中，该平台可收集实时 NIR 光谱并应用校准模型。PCA 测试成功检测到设备故障。还进行了变异分析，以估算在商业生产过程中 NIR 光谱法的采样分析误差，这些误差会影响结果。该系统用于监测和控制 28 小时的连续制造运行，其中 NIR 方法确定的平均药物浓度为标签声称的 101.17%，标准偏差为 2.17%，基于收集的 12633 个光谱。由这些混合物生产的片剂的平均药物浓度为标签声称的 100.86%，标准偏差为 0.4%，对 500 片进行傅里叶变换近红外（FT-NIR）透射光谱分析。混合物和生产的片剂中的平均药物浓度值之间的良好一致性进一步证明了所遵循的验证策略的适用性。
