کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5857704 1132024 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Application of the threshold of toxicological concern concept when applied to pharmaceutical manufacturing operations intended for short-term clinical trials
ترجمه فارسی عنوان
کاربرد آستانه مفهوم نگرانی سم شناسی در هنگام کاربرد عملیات تولید دارویی که برای آزمایشات بالینی کوتاه مدت مورد استفاده قرار می گیرد
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی

In the manufacture of pharmaceuticals, if a multiproduct facility shares equipment amongst drug substances/products it is incumbent upon the manufacturer to demonstrate removal of the pharmaceutical through a robust cleaning validation/verification program. Removal must be to below limits considered acceptable from a quality and toxicological perspective. In order to address the toxicological concerns, an acceptable daily exposure (ADE) was developed which is the “dose that is unlikely to cause an adverse effect if … exposed, by any route … at or below this dose every day for a lifetime” (ISPE, 2010). For compounds in development, defaulted ADEs were proposed by Dolan et al. (2005) and adopted by the International Society of Pharmaceutical Engineers (ISPE) as conservative cutoffs for compounds with limited data. In Phase 1 clinical trials, exposure is typically short-term (single dose or repeated doses for ≤30 days) compared to the chronic doses used to derive ADE and defaulted ADEs. An analysis of publicly available databases for toxicological and pharmacological effects supports the use of 10-fold higher defaulted values when the residual drug substance is in a developmental pharmaceutical intended for Phase 1 clinical trials (exposure ≤30 days).

► Expanded TTC dataset for a short-term pharmaceutical application. ► Developed a process which allows a 10-fold higher short-term TTC. ► Short-term TTC applicable to early clinical trial manufacturing.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 65, Issue 1, February 2013, Pages 162-167
نویسندگان
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