کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484935 | 1114340 | 2010 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A New Definition of Pharmaceutical Quality: Assembly of a Risk Simulation Platform to Investigate the Impact of Manufacturing/ Product Variabcpility on Clinical Performance
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A New Definition of Pharmaceutical Quality: Assembly of a Risk Simulation Platform to Investigate the Impact of Manufacturing/ Product Variabcpility on Clinical Performance A New Definition of Pharmaceutical Quality: Assembly of a Risk Simulation Platform to Investigate the Impact of Manufacturing/ Product Variabcpility on Clinical Performance](/preview/png/2484935.png)
چکیده انگلیسی
The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to “modernize” the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 12, December 2010, Pages 5046-5059
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 12, December 2010, Pages 5046-5059
نویسندگان
STEVEN M. SHORT, ROBERT P. COGDILL, FRANK D'AMICO, JAMES K. III, CARL A. ANDERSON,